The following information is missing from the Funding section: the Biotechnology and Biological Sciences Research Council grant no. BB/D526896/1.www.bbsrc.ac.uk) and the University of Sussex, and also an Alumni Travel Grant from the University of Sussex (www.sussex.ac.uk). KM was supported by a Leverhulme Trust Research Grant number RPG-2013-069 (www.leverhulme.ac.uk). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.The complete, correct Funding statement is: JW was supported by a studentship from the Biotechnology and Biological Sciences Research Council, grant no. BB/D526896/1 (BBSRC—In addition, the affiliations for the second and third authors are incorrectly switched. Anne M. Burrows is not affiliated with #2 but with #3, Department of Physical Therapy, Duquesne University, Pittsburgh, Pennsylvania, United States of America; Bridget M. Waller is not affiliated with #3 but with #2, Centre for Comparative and Evolutionary Psychology, Department of Psychology, University of Portsmouth, Portsmouth, United Kingdom.


Nepenthes L. Nepenthes are the largest of all carnivorous plants, and the species with the biggest pitchers are capable of trapping and digesting small amphibians and even mammals. The central cordillera of Mindanao Island in the south of the Philippines is mostly covered with old, primary forest and is the largest remaining cohesive, untouched area of wilderness in the Philippines. In a recent field exploration of two areas of the central cordillera, namely Mount Sumagaya and a section of the Pantaron range, four new taxa of Nepenthes were discovered. These four remarkable new species, N. pantaronensis, N. cornuta, N. talaandig and N. amabilis, are described, illustrated and assessed.Together with the islands of Sumatra (Indonesia) and Borneo , the Philippines are the main center of diversity for carnivorous pitcher plants of the genus,  Nepenthes. Local conflicts have hindered exploration of the islands in the past, and therefore, only 15 distinct species were known by the late 1990s [N. peltata Sh.Kurata and N. robcantleyii Cheek, were described based on cultivated material [N. viridis Micheler from Dinagat Island was described [N. graciliflora Elmer [N. extincta Cheek) might be “extinct in the wild, due to habitat destruction” [The Philippines are nowadays considered to host the highest diversity of carnivorous pitcher plants of the genus, material ,3. More escribed . The desra Elmer ,9,10,11 Nepenthes. Most species occur in the intermediate tropical highland climate prevalent on the numerous mountains of the islands. Diversity hotspots are mountains with ultramafic soils, such as Mt. Hamiguitan in Davao Oriental province  or the Diwata Mountains in Agusan del Norte.The islands of Mindanao and Palawan are the Philippines’ main centers of diversity for The most extensive mountain massif on Mindanao is the Pantaron mountain range, the major part of the central cordillera of Mindanao. It runs south from the municipality of Claveria in the north of the island towards the south to the municipality of San Fernando and separates the provinces of Bukidnon in the west and Agusan del Sur in the east. The average altitude of this mountain range is approximately 1,000 m, with summits of around 1,500 m that peak out of the cordillera. Almost the whole area is covered by dipterocarp, lower and upper mountain forest and is designated as a key biodiversity area by the Philippine Department of Environment and Natural Resources. The Pantaron range is flanked by the marshes of the Agusan River in the east and by the Pulangi River in the west, the latter being the longest river in Mindanao. Along the Pulangi River, large areas of lower mountain forest have been cleared for agriculture. West of the Pulangi River, opposite the Pantaron range, the Tago mountain range marks the western border of the central cordillera. The northern border of the central cordillera consists of a conglomeration of prominent peaks with altitudes significantly above 2,000 m, namely Mt. Sumagaya, Mt. Mangabon and Mt. Kimangkil. While other prominent mountains on Mindanao, like Mt. Apo, Mt. Kitanglad, Mt. Hamiguitan or Mt. Matutum have been explored extensively by local and foreign botanists, the central cordillera has remained unexplored until recently. Large areas of these mountains form part of the ancestral territories of local indigenous tribes, and separatist conflicts between the New People’s Army (NPA) and the military long hindered safe access to this remote area.N. mindanaoensis Sh.Kurata, N. merrilliana Macfarlane and N. truncata Macfarlane were found, as well as two remarkable new taxa that were previously unknown, N. pulchra Gronem. and N. ceciliae Gronem. [N. pulchra is an unusually large species that is related to N. petiolata Danser, whereas the gracile N. ceciliae shares features with N. copelandii Merr. ex Macfarlane and was subsequently grouped with the N. alata complex of species [A minor peak in the Pantaron range in the San Fernando area was explored by one of the authors in 2008 , and Mt. Gronem. ,14. N. p species ,8. N. surigaoensis Elmer, on minor peaks in the Pantaron range near San Fernando [These findings, together with the identification of several species, including Fernando , led to Nepenthes taxa. The taxonomic descriptions of these new species are provided in this article. In order to verify this theory, an area of the Pantaron range approximately 60 km north of San Fernando and Mt. Sumagaya, one of the high peaks forming the northern border of the central cordillera, were chosen for further field research. This expedition led to the discovery of four additional new Nepenthes pantaronensis Gieray, Gronem., Wistuba, Marwinski, Micheler, Coritico, V.B. Amoroso, spec. nov.N. pulchra Gronem. in having 2 longitudinal nerves (N. pulchra: 3–4), 2 non-fringed or barely fringed wings on the lower pitchers and no wings on the upper pitchers (N. pulchra: fringed wings on the lower pitchers and wings reduced to ribs on the upper pitchers) and in having basal stem leaves with a canaliculate petiole (N. pulchra: broad-winged petiole). Differs from T. Gronemeyer and F. Coritico, holotype CMUH00008625, Central Mindanao University Herbarium (CMUH), Musuan, Bukidnon, Philippines. Philippines, Mindanao Island, Bukidnon Province, Pantaron mountain range, Mt. Gaka  near Sitio Mahayag , 15.08.2012, N. pantaronensis was discovered in the Pantaron mountain range. The specific epithet denotes that stem is up to 3 m long, cylindrical in the cross-section, 0.9–1 cm in diameter, with internodes up to 13 cm long.The Leaves of the basal stem are linear to oblong, up to 28 cm long and 5 cm wide, with two longitudinal veins on each side of the midrib and numerous pinnate veins running obliquely towards the leaf margins. The apex of the lamina is acute, the base attenuate and forming a canaliculate petiole that is strongly decurrent down the full length of the internode. The tendrils are up to 34 cm long and mostly coiled. All parts of the foliage may be yellowish green.Leaves of the climbing stem form a broad-winged petiole that is also strongly decurrent. In all other respects, they are consistent with the leaves of the basal stem.Lower pitchers are up to 35 cm tall and 6 cm wide, though usually smaller. The bottom quarter to third of the pitcher is variably inflated, sometimes to the extent that the basal part is bulbous. Above the broad lower section, the pitcher narrows, becoming cylindrical or very slightly infundibular towards the pitcher opening. Wings are usually reduced to ribs, although occasionally, some fringes are present below the pitcher opening. The pitcher opening is oblique and up to 5 cm wide. The peristome is flattened, up to 2.5 cm wide and particularly broad around the sides and below the lid. The peristome is lined with ribs up to 2 mm high, spaced up to 2 mm apart. The ribs are elongated on the inner edge of the peristome to form narrow teeth up to 3 mm long. The lid is ovate, up to 7 cm long and 6 cm wide, with glands densely and evenly distributed over the lower surface. A prominent, triangular, hooked and keeled appendage up to 5 mm long is present on the underside of the lid. The spur is unbranched and up to 5 mm long. The exterior of the lower pitchers is greenish or slightly orange, with narrow orange-red blotches. The interior of the pitcher is white or light yellowish green, lined with small, angular blotches of purple-red. The peristome is red, variably striped with bands of yellow, orange and purple. The lower and upper surface of the lid is bright red.Upper pitchers are up to 40 cm long and 5 cm wide, though usually smaller. The bottom fifth to quarter of the trap is inflated and bulbous, narrowing above this part before becoming cylindrical towards the pitcher opening. Some of the upper pitchers are narrower above the bottom fifth to quarter of the trap, while others are almost cylindrical with almost no narrowing. Wings are indiscernible. The peristome is up to 1 cm wide, cylindrical or slightly flattened, lined with ribs up to 1 mm high, spaced up to 1 mm apart. In all other aspects, including coloration and color variability, the upper pitchers are consistent with the lower ones, although some upper pitchers are entirely green with no blotches.inflorescence is a panicle, up to 29 cm long, composed of a 19.5 cm-long scape and an additional 9.5 cm rachis bearing pedicels evenly scattered along its length. The pedicels are about 2 cm long, branched and one- or two-flowered. Bracts are absent.The Indumentum is present across the foliage, inflorescence and pitchers, consisting of orangey brown hairs up to 1 mm long. N. pantaronensis  in the northeast of Mindanao and grows mainly epiphytically. N. pulchra represents the most western species and is currently known only from Mt. Kiamo in the Tago range, where it grows terrestrially on ultramafic soils. N. pantaronensis is located in between these two species  and represents a true intermediate between these two; it grows both epiphytically and terrestrially  and has both canaliculate and winged petioles, the former on the basal stem and the latter on the climbing stem. ronensis  is close pulchra  and N. petiolata . The mosetiolata , these tf Danser  and reprNepenthes cornuta Marwinski, Coritico, Wistuba, Micheler, Gronem., Gieray, V.B.Amoroso, spec. nov. N. copelandii Macfarlane in having a narrower lamina, upper pitchers with a distinctive, swollen base and an almost completely cylindrical upper two-thirds  and noticeably smaller lower pitchers lacking wings .Differs from T. Gronemeyer and F. Coritico, holotype CMUH00008547, Central Mindanao University Herbarium (CMUH), Musuan, Bukidnon, Philippines. Philippines, Mindanao Island, Bukidnon Province, Pantaron mountain range, trail from Sitio Mahayag  to Sitio Balaudo, 15.08.2012, cornuta (lat. cornu = horn), refers to the plant’s horn-shaped upper pitchers.The specific epithet, stem is up to 3 m long and 7 to 8 mm in diameter; the internodes are 4 to 5 cm long.The Leaves of the climbing stem are petiolate and linear to lanceolate, up to 30 cm long and 4.5 cm wide. The apex of the leaf blade is acute, the leaf base broadly attenuate and petiolate. The petiole is up to 4 cm long, canaliculate and amplexicaul, clasping between one third and half of the stem. Three parallel longitudinal nerves run on each side of the midrib, on the outer half of the lamina. The tendrils can reach up to 24 cm in length. The foliage and the midrib are green or yellowish green, while the stem and the tendrils can take on a slight red hue when growing in full sunlight.Lower pitchers are up to 15 cm long and 3.4 cm wide. The pitcher opening is ovate and up to 2.8 cm in diameter. The pitcher’s bottom third is bulbous; above this part, the pitchers narrow, sometimes forming a faint hip and becoming cylindrical to slightly infundibular towards their opening. The lid is up to 3.2 cm long, 2.8 cm wide and ovate. The appendage is reduced to a rudimentary keel of up to 1 mm. The spur is up to 3 mm long. The gland distribution is unknown. The peristome has a cylindrical cross-section of up to 5 mm in diameter, positioned at an angle and is lined with very fine ribs. The wings of the pitchers are reduced to ridges, usually without fringes. Occasionally, a few fringes can appear on the top end of those ridges, just below the peristome. The pitchers are green in their bottom third, sometimes taking on a yellowish hue towards the pitcher opening, whilst the upper two-thirds of the pitchers are mottled with red or maroon blotches. The peristome is yellowish to orange or reddish with fine red stripes. The lid is red to maroon with yellowish blotches.Upper pitchers are up to 20 cm long and 4.5 cm wide, the pitcher opening being the widest part. The bottom third is swollen to varying degrees, sometimes displaying a faint hip, and tapers towards the tendril, giving the pitcher its typical, horn-shaped appearance. Above this part, the pitcher narrows faintly and becomes almost completely cylindrical or slightly infundibular towards its opening. The narrowing between the swollen base and the upper part of the pitcher is less pronounced than in the lower pitchers. The lid is up to 5 cm in diameter, ovate to cordate and lacks an appendage. The glands are evenly distributed across the lower surface of the lid. The spur is up to 8 mm long. The peristome is oblique and has a cylindrical cross-section of 5 to 7 mm in diameter. The wings are reduced to inconspicuous vestigial ridges. The pitchers are always green or yellow, except for the interior and the bottom side of the lid, which can have red to maroon speckles. The peristome is green or yellow, often with fine red stripes.inflorescence is a predominantly two-flowered rachis up to 40 cm long sitting on a scape of up to 21 cm. The individual pedicel can measure up to 15 mm. Bracts are absent.The Indumentum is absent from stems, leaves, pitchers and flowers, but the developing pitcher buds are covered with minute, orangey brown hairs.N. cornuta  and having a winged petiole that clasps the stem . Differs from T. Gronemeyer and F. Coritico, holotype CMUH00008624, Central Mindanao University Herbarium (CMUH), Musuan, Bukidnon, Philippines.Philippines, Mindanao Island, Bukidnon Province, Pantaron mountain range, trail from Sitio Mahayag  to Sitio Balaudo, 15.08.2012, N. talaandig occurs on the ancestral territory of the Talaandig communities of east Bukidnon. The specific epithet was chosen to acknowledge the indigenous tribe of the Talaandig. The stem is up to 8 m long, cylindrical in the cross-section and 7–8 mm in diameter. The internode length is 3.5–6 cm. Leaves of the climbing stem are elliptic, up to 35 cm long and 4.5 cm wide, with four equally distributed longitudinal veins on each side of the midrib and numerous pinnate veins running obliquely towards the leaf margins. The apex of the lamina is acute, the base attenuate and forming a narrow-winged petiole 6 cm in length that clasps one third of the stem. Pitchers are on tendrils 16–20 cm long. Lower pitchers are bulbous or ovate, 10 cm tall and 5 cm wide. The pitcher narrows slightly towards the opening. Wings are up to 7 mm wide, fringed with filaments up to 7 mm long and run down the front of the trap. The pitcher opening is at a prominent angle, up to 3.5 cm wide and acuminates towards the lid. The peristome is flattened, up to 1.5 cm wide and crenellated. It extends into a neck towards the lid and is densely lined with ribs approximately 1 mm high. The lid is ovate to cordate, up to 5.5 cm long and 5 cm wide, with glands evenly distributed across the lower surface. A rounded, triangular appendage up to 3 mm long, sitting on a keel, is present on the underside of the lid. The spur is branched and up to 6 mm long. The exterior of the lower pitchers is rusty red to violet, with narrow blotches of reddish purple. The interior of the pitcher is white and sometimes lined with angular blotches of purple. The peristome is dark red and not striped. Rosette pitchers, which are squatter and considerably smaller than the lower pitchers, have been observed in situ on young plants. In all other respects, they resemble the lower pitchers. Upper pitchers are slender, around 20 cm long and 7 cm wide. The bottom third of the trap is slightly inflated. The pitcher narrows towards a cylindrical middle section before it widens towards the oblique pitcher opening; the latter being 4.5 cm wide. Wings are reduced to ribs throughout. The peristome is not crenellated, is cylindrical to flattened, up to 1.2 cm wide and extends into a short neck. The color of the peristome is yellow with discrete stripes of red. The lid is ovate to orbicular with a diameter of 4 cm. A prominent triangular appendage of 2.5 mm on a keel is present; the spur is 6 mm long and branched. The upper pitchers are colored yellowish-green, often with red speckles or blotches. The pitcher interior is cream-colored without blotches. inflorescence is a panicle, composed of a rachis up to 40 cm long sitting on a 20-cm scape. It bears branched two-flowered partial peduncles 5 mm long. Bracts are present. The Indumentum is sparse, if present at all. N. talaandig  [alaandig  is not dsurface) .Nepenthes amabilis Wistuba, Gronem., Micheler, Marwinski, Gieray, Coritico, V.B.Amoroso, spec. nov. N. pantaronensis Gieray in having spathulate-ovate, approximately 10 cm long and 3.5 cm wide leaves with an obtuse apex (N. pantaronensis: up to 28 cm long and narrowly acute apex) and having mostly cylindrical to slightly infundibular upper pitchers that are only 10–15 cm tall and distinctly contracted in the region below the peristome . Differs from T. Gronemeyer and A. Wistuba, holotype CMUH00008635 , isotype CMUH00008637 , Central Mindanao University Herbarium (CMUH), Musuan, Bukidnon, Philippines.Philippines, Mindanao, Mt. Sumagaya, trail from Barangay Mat-I  to the summit 19.08.2012, amabilis (lat. amabilis = lovely), refers to the extraordinary beauty of the compact specimens with very colorful pitchers and mostly striped peristomes that were observed in situ. The specific epithet, stems are often very short. Plants start to grow upright at a young age and are supported by surrounding vegetation, mostly low shrubs. The stem of short plants is green and often almost without any significant internodes. Occasionally, in more shady locations and where the stems can scramble along other plants as support, plants develop climbing stems that reach 2–3 m in length. These vines are almost round in the cross-section, 8 mm in diameter, green to dark red and with internodes that are 10–15 cm long.The Leaves of the vines and short stems are broadly spathulate-ovate, 10 cm long and 3.5 cm wide, with a broad, winged and 1 cm-wide petiole. The leaves are green with yellowish to reddish midribs. The leaf attachment is decurrent, running 1–3 cm down the stem. One to two longitudinal nerves run parallel to the midrib in the outer half of the lamina. Pitchers are attached to tendrils up to 13 cm long.Lower pitchers of rosette plants are unknown; plants with lower pitchers could not be identified with certainty at the type locality. Upper pitchers of short and climbing stems are 10–15 cm high, approximately 3 cm wide, mostly cylindrical, slightly infundibular in the lower third and distinctly contracted in the region below the peristome. The bottom fifth is often slightly ventricose with a slight waist above. The pitcher wings are reduced to ribs. Only occasionally in some pitchers, approximately 5 mm-wide wings bearing two or three fringes measuring approximately 5 mm in length are visible close to the peristome. The peristome is cylindrical and approximately 4 mm wide. The spur on the pitcher lid is unbranched, filiform and 3 mm long. The pitcher mouth is round, slightly elevated at the front and elongated towards the back with a slightly developed neck. The lids are 3 cm long, 3.5 cm wide, orbicular, sometimes with a small appendage near the base of the lid, which is mostly reduced to a keel. The glands are evenly distributed across the lower surface of the lid. The exterior of the upper pitchers is yellowish green to orange, unevenly suffused with red or with red blotches. The interior of the pitcher is whitish with numerous purple blotches that often shine through the pitcher wall. The peristome is yellowish green with numerous red stripes. The lid is yellowish with numerous red blotches.inflorescence is a panicle composed of a 15 cm-long scape and an additional 15 cm rachis bearing two-flowered, 20 mm-long pedicels. The anther column is up to 14 mm and the ovary 5 mm long, containing ripe seeds; the tepals are up to 7 mm long and ovate. The indumentum is present across the foliage, the inflorescence, especially the margins of young leaves, and pitchers, consisting of brownish hair up to 1 mm long.A prominent N. amabilis  were found in dead or dying pitchers of this species. The ants obstruct the pitcher opening with a greyish matter, probably made out of vegetal detritus and dirt. This ‘lid’ has small entry holes along the pitcher walls. The bottom of the pitchers is pierced with one or two round holes, draining them of their digestive fluid. These holes also serve as “emergency exits” for the ants when disturbed. The presence of those insects on some pierced functional pitchers without a nest might suggest that the ants first pierce and drain functional pitchers before colonizing them. A similar colonization has been observed before in other Nepenthes species, e.g., N. macfarlanei Hemsl. in Malaysia [N.maxima Reinw. on the lower slopes of the Maoke Mountains in West Papua .At the type locality of Malaysia  and N.mNepenthes spp. is low. The Pantaron range is currently visited only by the indigenous people of the Talaandig tribe, who cross the mountains to reach remote, temporarily inhabited villages or with the purpose of hunting and collecting rattan or resin. The impact of poaching on the population of Nepenthes spp. in this region.However, the foothills of the Pantaron range are completely deforested for agriculture, and illegal logging may take place in the forests. Therefore, habitat destruction has the biggest impact on the population of the N. talaandig and N. cornuta are widely distributed in the Pantaron range, as they do not occur on isolated peaks. Since only few data have been recorded about the distribution of N. talaandig and N. cornuta, these two taxa are assessed here as VU (vulnerable) according to the IUCN Red List criteria [It may be anticipated that both criteria . N. pantaronensis is known both from the Pantaron range and Mt. Sumagaya, and thus, a wider distribution is documented. It is assessed here as NT (near threatened). N. amabilis is currently only known from the upper slopes of Mt. Sumagaya. It has not been recorded in the explored areas of the Pantaron range, nor on Mt. Kiamo in the Tago range. Mt. Sumagaya is only visited by the indigenous people of the Higaonon tribe, who cross the mountains to hunt deer, and by dispersed groups of the NPA who hide in the mountains. The impact of poaching is low. However, as no comprehensive data about the distribution of this taxon have been recorded, it is classified here as EN (endangered). Field research was carried out during August, 2012. All data and dimensions were either collected in the field from live plants or from the respective herbarium types cited above.The Pantaron range in the area of Barangay St. Peter  was explored after an access permit was granted by the Bukidnon Resource Management Foundation and the Biodiversity Management Bureau (BMB) of the Department of Environment and Natural Resources (DENR), and with the consent of the local indigenous people of the Talaandig tribe. Mount Sumagaya was explored with the consent of the local military authorities in Barangay Mat-I  and the local indigenous people of the Higaonon tribe.Herbarium specimens were collected under a collection permit granted to VB (Permit No. MOA 10-2-5 from 2012). in situ and processed subsequently using standard methods at the herbarium of the Central Mindanao University.Cropped plant material was placed between paper sheets in situ.Photographs were made from suitable, representative plant specimens Image credits: Botanical drawings in Carnivorous pitcher plants are widespread within the Malesian biogeographical region comprising the Malayan peninsula and the islands of Sumatra, Borneo, Sulawesi and the Philippines. Especially in the Philippines, the majority of species are known from centers of diversity and endemism. Several species are restricted to one single mountain top or a mountain ridge. N. amabilis, N. cornuta, N. pantaronensis and N. talaandig. A field research trip to the formerly unexplored central cordillera of Mindanao led to the discovery of four new taxa of carnivorous pitcher plants, namely N. cornuta and possibly N. talaandig belong to the N. alata group of species, N. pantaronensis is clearly related to N. pulchra and N. petiolata and, thus, belongs to the Reginae group.While N. amabilis stands clearly on its own among the Philippine Nepenthes species. N. ceciliae, N. pulchra, N. surigaoensis and N. truncata. However, the latter two species are widespread and also occur in other regions of Mindanao.Other species in the central cordillera include Nepenthes in the Philippines, the future of all species of the central cordillera is highly dependent on habitat conservation. Mt. Kiamo is not currently a protected area and, thus, the conservation status of the two endemic species, N. ceciliae and N. pulchra, needs to be monitored closely in the future. As with many other species of Nepenthes species we described in this article would be assured preservation in the long term. If the current status “key biodiversity area” for the Pantaron range and the Kimangkil massif, including Mt. Sumagaya, leads to permanent protection combined with careful monitoring of the relevant protective measures, at least the four endemic


C. Gilchrist. Gilchrist initially believed the disease was caused by a protozoan, but in collaboration with W.R. Stokes, he subsequently isolated the organism, which he named Blastomyces dermatitidis. The infection became known as Chicago disease because most early cases were identified in the Chicago area, but it was subsequently shown to be endemic to much of eastern North America. Sporadic cases have also been reported in Africa, the Middle East, and India.From the Greek


The supplementary motor area (SMA) syndrome is a characteristic neurosurgical syndrome that can occur after unilateral resection of the SMA. Clinical symptoms may vary from none to a global akinesia, predominantly on the contralateral side, with preserved muscle strength and mutism. A remarkable feature is that these symptoms completely resolve within weeks to months, leaving only a disturbance in alternating bimanual movements. In this review we give an overview of the old and new insights from the SMA syndrome and extrapolate these findings to seemingly unrelated diseases and symptoms such as Parkinson’s disease (PD) and tics. Furthermore, we integrate findings from lesion, stimulation and functional imaging studies to provide insight in the motor function of the SMA. The supplementary motor area (SMA) syndrome is a characteristic neurosurgical syndrome that may occur after unilateral resection of the SMA. The classical SMA syndrome, following unilateral resection of the SMA, is characterized by a global akinesia with normo- or hyporeflexia and a normal tonus, more profound on the contralesional side, while muscle strength can be preserved . Here wThe SMA or SMA proper (Brodmann area 6) is localized in the posterior part of the superior frontal gyrus  and tics. Combining these findings, we propose that the SMA is involved in both the initiation and suppression of movements, maintaining a tonic interhemispheric balance.A hallmark of the SMA syndrome that is always described is a severe neurological deficit of temporary nature; only subtle deficits are permanent. Although the precise mechanisms underlying the recovery after the initial deficit remain obscure, the syndrome provides useful insights in the functioning of the SMA. The occurrence of the different deficits of the SMA syndrome following resection is consistent with the somatotopical organization of the SMA (Fontaine et al., Effort has been undertaken to understand the mechanisms underlying the recovery. Functional reorganization due to brain plasticity has been brought up in order to understand the temporary deficits. A lesion in the SMA leads to more activation of the contralateral SMA (Sailor et al., In summary, clinical deficits after resection of the SMA may vary from none to a global akinesia with mutism. On the one hand, this finding emphasizes the heterogeneity associated with lesion studies, particularly in cerebral infarcts, but also after resection of tumors that are not always completely restricted to the SMA. On the other hand, the heterogeneity in clinical symptoms after resections may be caused by variability in preoperative reorganization of function due to brain plasticity.It is evident that preoperative reorganization of cerebral function does not completely account for the recovery, because the reversibility of the SMA syndrome is also seen in patients with acute lesions such as an infarct or patients that undergo surgery for epilepsy (Yamane et al., It is remarkable that although the other more striking deficits of the SMA syndrome completely resolve, difficulties in alternating bimanual movements persist. We focus on bimanual alternating movements here, because this impairment is well described in patients with the SMA syndrome. Disturbed alternating movements of the lower limbs have also been described (Laplane et al., Although PD is a chronic deteriorating disease and the SMA syndrome is acute, some parallels can be seen between these disorders. PD is caused by a loss of dopaminergic neurons in the pars compacta of the substantia nigra (Gibb and Lees, As in the SMA syndrome, patients with PD show a disturbance in the performance of alternating movements (Dick et al., The SMA has been shown to be active during the selection of movements and word generation when there are no external cues, while the lateral premotor cortex is activated when there are cues (Passingham, Indeed, the pathophysiology underlying the SMA syndrome and PD are completely different. Nevertheless, the phenomenology can help in understanding the function of the SMA. For example, a patient has been described with a low-grade glioma in the left SMA that caused a Parkinsonian syndrome, characterized by akinesia, rigidity, a resting tremor and micrographia (Straube and Sigel, Direct electrical stimulation of the SMA can lead to inhibition of movement or speech arrest, while it can also evoke movements, the urge to move or vocalizations (Penfield and Welch, How should this apparent discrepancy between lack of movement initiation after lesions of the SMA and inhibition of movements due to an increased activity in the SMA be integrated? We recognize that any explanation remains hypothetical, but it may offer grip for further understanding. Lesions of the SMA are sometimes accompanied by temporary grasp reflexes or even an alien hand syndrome (Goldberg et al., As previously mentioned, stimulation of the SMA can evoke movement initiation as well as an arrest in movements. Moreover, the SMA is active during the sight of a graspable object (Grèzes and Decety, Furthermore, our hypothesis is consistent with the fact that the SMA can both initiate and suppress movement after a sensory instruction (Kurata and Tanji, This tonic regulation can also explain the deficit in bilateral alternating movement patterns following unilateral lesioning of the SMA, while mirror movements are preserved (Bleasel et al., The tonic interhemispheric balance could also be an explanation for the above-mentioned apparent disparity between activation of the SMA that leads to suppression of tics, while inhibition of the SMA reduces tic frequency and activation of the SMA in healthy controls can lead to echophenomena.Our model has a focus on the initiation and inhibition of movements with a special interest in bimanual alternating movements. It has been shown that there are more NMAs, for example in/near other premotor areas (Mikuni et al., The SMA syndrome is an intriguing syndrome, characterized by temporary dysfunction, that helps to obtain useful insights in the function of the SMA and its embedment in neuronal circuits. The main aim of this article was not to write a comprehensive review on the function of the SMA, as these are available. Here we summarized the findings from previous studies regarding the SMA syndrome and showed that there are analogs with seemingly very different disorders such as PD and tics. Combining these findings, we propose that the SMA is involved in both the initiation and suppression of movements, maintaining a tonic interhemispheric balance. In this physiological context, the presentation of temporary deficits of the SMA syndrome supports the view that the healthy SMA can compensate for the functional impairment inflicted by the affected SMA. This concept is further supported by the persistent impairment of performing bimanual anti-phase movements, a motor condition in which such compensation apparently fails due to a strong simultaneous demand on both SMA’s.Conception of the work: A. R. E. Potgieser.Design of the work: A. R. E. Potgieser, B. M. de Jong, M. Wagemakers, E. W. Hoving, R. J. M. Groen.Interpretation of the work: A. R. E. Potgieser, B. M. de Jong, M. Wagemakers, E. W. Hoving, R. J. M. Groen.Drafting the work: A. R. E. Potgieser.Revising critically for important intellectual content: A. R. E. Potgieser, B. M. de Jong, M. Wagemakers, E. W. Hoving, R. J. M. Groen.Final approval of the version to be published: A. R. E. Potgieser, B. M. de Jong, M. Wagemakers, E. W. Hoving, R. J. M. Groen.Agreement to be accountable for all aspects of the work: A. R. E. Potgieser, B. M. de Jong, M. Wagemakers, E. W. Hoving, R. J. M. Groen.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.


Despite biological advantages of male circumcision in reducing HIV/sexually transmitted infection acquisition, concern is often expressed that it may reduce sexual enjoyment and function. We examine the association between circumcision and sexual function among sexually active men in Britain using data from Britain's third National Survey of Sexual Attitudes and Lifestyles . Natsal-3 asked about circumcision and included a validated measure of sexual function, the Natsal-SF, which takes into account not only sexual difficulties but also the relationship context and overall level of satisfaction.n = 4816).A stratified probability survey of 6293 men and 8869 women aged 16–74 years, resident in Britain, undertaken 2010–2012, using computer-assisted face-to-face interviewing with computer-assisted self-interview for the more sensitive questions. Logistic regression was used to calculate odds ratios (ORs) to examine the association between reporting male circumcision and aspects of sexual function among sexually active men : 19.3–21.8]. There was no association between male circumcision and, being in the lowest quintile of scores for the Natsal-SF, an indicator of poorer sexual function . Circumcised men were as likely as uncircumcised men to report the specific sexual difficulties asked about in Natsal-3, except that a larger proportion of circumcised men reported erectile difficulties. This association was of borderline statistical significance after adjusting for age and relationship status .Data from a large, nationally representative British survey suggest that circumcision is not associated with men's overall sexual function at a population level. The WHO states that there is compelling evidence to show that male circumcision reduces the risk of heterosexually acquired HIV and recommends that it is promoted as part of a comprehensive HIV prevention package . HoweverIn this article, we report analyses of data from the third British National Survey of Sexual Attitudes and Lifestyles , a large national probability survey, which used a new, comprehensive, validated measure of sexual function, the Natsal-SF ,7, allowFull details of the methods of the Natsal-3 have been reported elsewhere ,9. Brief‘I have avoided sex because of sexual difficulties, either my own or those of my partner’ , and reporting ever taking any type of drug to assist sexual performance.We used an overall measure of sexual function – the Natsal-SF, which is a 17-item validated measure developed for Natsal-3 ,7. It inWe used Stata, version 12  for all statistical analyses to account for the stratification, clustering, and weighting of the Natsal-3 sample. Data were weighted to match the resident British population according to the Census in terms of sex, age, and geographic region such that the weighted sample can be considered broadly representative of the British population ,9.a priori. As numbers were small in some of the categories of ethnicity and religion wherein circumcision was more common, and combination of ‘non-white’ ethnicities and ‘non-Christian’ religions would have made too heterogeneous a group, we decided not to adjust for either ethnicity or religion after confirming that additional adjustment for ethnicity and religion affected the ORs only minimally. In addition, education did not confound the associations between circumcision and sexual function and so was not included in the adjusted model. The Natsal-3 study was approved by the Oxfordshire Research Ethics Committee A (reference: 09/H0604/27).Logistic regression was used to calculate odds ratios (ORs) to assess associations between circumcision status and the measures of sexual function mentioned previously. We used multivariable logistic regression to calculate adjusted OR (AOR) to adjust for the confounding effect of age and relationship status Of the 6293 men aged 16–74 years who participated in Natsal-3, 6117 (97.4%) reported whether they were circumcised, such that the prevalence of circumcision in the British male population is estimated as 20.7% (95% CI: 19.3–21.8). In total, 4816 of these 6117 men (78.7%) reported that they had at least one sexual partner in the year prior to interview and so were considered sexually active and included in the remaining analyses. Men who were sexually active were less likely to be circumcised ; however, after adjustment for age, there was no association between circumcision status and being sexually active . Table Among sexually active men, there was no association between reporting having been circumcised and being categorized as in the lowest quintile of the Natsal-SF, an indicator of poorer sexual function overall , a finding that persisted when the denominator was expanded to include all men (data not shown). There was also no difference by circumcision status in the proportion of men who reported ever taking performance-enhancing drugs to assist their sexual performance.Data from this large, national probability survey show that, among sexually active men in Britain, those who were circumcised were no more likely to have poor sexual function as measured by the Natsal-SF ,7 than uStrengths of this study include the large sample size and the use of probability sampling, allowing us to present findings broadly representative of the British general population ,9. We reAs a survey addressing all aspects of sexual health and well-being, Natsal-3 did not have the scope to ask detailed questions about particular experiences of sexual function, for example, penile sensitivity. However, an important strength here is the holistic conceptualization of sexual function as captured by the Natsal-SF, allowing us to take into account not only sexual response, but also the relationship context and men's overall level of satisfaction. In addition, we did not have sufficient numbers of men reporting male partners within the past year to explore whether the associations between circumcision and sexual function varied by partner gender.The lack of any observable association between circumcision and sexual function in this cross-sectional survey is in keeping with the conclusions from a large systematic review of male circumcision and its effect on men's sexual function, sensitivity, and satisfaction . HoweverThe authors would like to thank the study participants, the team of interviewers from NatCen Social Research, and operations and computing staff from NatCen Social Research.V.H., C.T., K.R.M., R.F.M., and C.H.M. conceived this article. V.H. wrote the first draft of the article, with further contributions from all other authors. V.H. did the statistical analysis, with support from C.T. and C.H.M. W.M., K.W., P.S., A.M.J., and C.H.M., initial applicants for Natsal-3, wrote the study protocol and obtained funding. C.T., K.R.M., N.F., W.M., K.W., P.S., A.M.J., and C.H.M. designed the Natsal-3 questionnaire, applied for ethics approval, and undertook piloting of the questionnaire. C.T. and C.H.M. managed data. All authors interpreted data, reviewed successive drafts, and approved the final version of the article.Natsal-3 is a collaboration between University College London , the London School of Hygiene and Tropical Medicine , NatCen Social Research, Public Health England , and the University of Manchester .Sources of any support for the work in the form of grants, equipment, drugs, or any combination of these: N.F. is supported by a National Institute for Health Research Academic Clinical Lectureship.Disclose funding received for this work from any of the following organizations: National Institutes of Health (NIH); Wellcome Trust; Howard Hughes Medical Institute (HHMI); and other(s): Natsal-3 was supported by grants from the Medical Research Council (G0701757) and the Wellcome Trust (084840), with contributions from the Economic and Social Research Council and Department of Health.Disclaimers: A.M.J. has been a Governor of the Wellcome Trust since 2011. The other authors declare that they have no conflicts of interest.


Morpho butterflies are well known for their high reflectance, which appears to remain high over a wide range of viewing angles. Thus these butterflies have served as the inspiration for sensing materials. Using microscopic images and videos, we visually demonstrate that the colour response with ambient refractive index of Papilio blumei is better than that of Morpho rhetenor. This result was also verified using measurements of the reflectance for different viewing angles. The finite-difference time-domain method was then used to simulate the microscopic pictures and reflections. Finally, the relationships between the structure, ambient refractive index, reflection and viewing angle are discussed in detail.Multilayer structures are known to produce vivid iridescent colouration in many butterflies.  Nanofabrication has been successful in creating photonic structures for chemical and biological detection12317891011Morpho typeUrania typeMultilayer structures are known to produce vivid iridescent colouration in certain butterflies1314Morpho butterflies are rather unique in their high reflectance and in that their reflectance appears to remain high over a wide range of viewing angles, contrary to what is often observed from other natural examples of structural colours. This iridescence has been studied both in measurement and modelling techniques17Morpho butterflies has been investigated for use in sensing materials7911The swallowtail family of butterflies (subfamily Lepidoptera of the family Papilionidae) is particularly renowned for its striking colour. Among the swallowtail butterflies, the brilliant green wings are found. The wing scales of of these butterflies consist of regular concave multilayer stack that are made from alternating chitin and chitin-air layers. One interesting phenomenon produced by this structure is that when placing the wing scales between crossed polarizers, light reflected off the centres of the cavities is suppressed, whereas retro-reflected light from four segments of the cavity edges is detected1921222325262728Morpho butterflies in ethanol have been investigated by several researchers730Morpho butterflies produce remarkably diverse differential reflectance spectra, achieving a highly selective response to different ambient refractive indices. In this paper, we will demonstrate that the response of Papilio blumei (P.B.) is better than that of Morpho rhetenor (M.R.) both in reflective intensity and viewing angle range.The optical properties of P.B. (class II) and M.R. (class I) respectively, were chosen for this study. We demonstrated the obvious changes in colour with volatilization of butterfly scales in ethanol. The reflective properties of these structures with different viewing angles were also studied. While both structure types were very sensitive to ethanol, the most interesting result was that the sensitivity of P.B. was very different than that of M.R.. This difference in colour response with ambient refractive index (RI) arose as a result of their different structures. We then simulated the optical responses of the volatilization of two different structures using the finite-difference time-domain (FDTD) method. The simulation results reproduced the experimentally observed reflections, including the reflections observed for different viewing angles. We found that the colour response with ambient RI of the concave structure is better than that of the tree-like structure, and thus we performed a number of additional simulations to investigate the reason for this difference. Finally, the key parameters of the concave structure were identified to assist in the design of the sensing materials.The concave structure and the tree-like structure of P.B. and M.R. The colour of P.B. changed greatly, from dark yellow to green, while the colour of M.R. changed from green to blue. The whole process of volatilization is shown in the video files in the P.B. being more vigorous than that of M.R.. It is generally understood that these colour responses are result of their structure. Thus detailed simulations were performed to investigate the difference in the colour response of the two types of structure.P.B. and M.R. are dependent on viewing angle. Thus the viewing angle dependence of both colour responses were measured. As shown in M.R. in air and in ethanol shifted from 27° to 24°, which is a fairly small shift. A similar result for M.R. was derived from experimental data (using only 488 nm incident light)P.B. in air and in ethanol is shifted from 60° to 5° as shown in M.R.. Also we can see that the viewing angle range of P.B. is larger than that of M.R. in air, while the viewing angle range of M.R. is bigger than that of P.B. in ethanol. Thus the colour response of P.B. is more vigorous than that of M.R.. The reasons for this phenomenon will be discussed subsequently.The colours of The models shown in 223132In order to study the colour response of the volatilization of both structures, we defined a liquid level x1 range from 0 nm to 5000 nm as shown in The angular dependence of the colour response of both structures discussed above is shown in P.B. than for M.R..Reflectance spectra for different field angles (θ) of the concave structure are shown in In order to display the relationship between the RI and the field angle more clearly, reflectance spectra for different ambient RI are shown in The viewing angle dependencies of multilayer structure to concave structure were measured and simulated as described above. Here we examine this issue in further detail, as shown in The concave structure has a vigorous colour response for different ambient RI as discussed above. This colour response is relative to the field angle. As shown in The electric field map is presented in Digital microscopes achieve a larger depth-of-field than optical microscopes, allowing for accurate observation of a target with a highly uneven surface. In this study, the vivid observations and the corresponding video files of the colour response with different reflective indices were therefore obtained using a digital microscope. To make the results comparable to each other, the data were obtained under identical conditions, e.g. of brightness and depth-of-field.Angle-dependent reflectance spectra of the butterflies were acquired with an angle-resolved reflectance measurement setup based on a pair of optical fibres that could be rotated independently around the same axis, one acting as the light source, the other as the light collector. A stabilized halogen light source were used for reflectance measurements. The butterflies were placed with their ridges parallel to the rotation axis, and the light reflectance spectra were measured as a function of the viewing angle. To measure the iridescence, the fibres of the light source were set at 10° from the centre, and the fibres of the light collector was rotated in opposite, equally spaced steps of 10° from 0° to 60°.In order to reproduce the colour response of the butterflies we converted reflection into colour maps. Let us suppose that the butterfly is illuminated by an illuminant characterized by its energy distribution D(λ). In this paper, we use the CIE  normalized illuminant D65, which closely matches that of the sky daylightAt this stage, we have replaced a complicated set of data (i.e. the spectrum R(λ)) by a colour point in a colour map. As illustrated in the above sections, this representation can be very useful for obtaining the dynamic reflection properties. A two-dimensional colour-map based on this representation has two free parameters (for example the dynamic reflection of the butterfly with the process of volatilization).M.R. and P.B. nanostructure. In the optical model, we took into account two contributors to the optical changes: (i) the two different structure types (ii) a change in the refractive index induced by volatility. The scales of these two butterflies are formed largely from chitin, whose refractive index was assumed to be 1.56 + i0.063132M.R. were obtained from electron microscopy studies31P.B. were obtained from electron microscopy studiesTo theoretically validate the nature of the optical response, we performed optical and volatile modelling of the W.L.W. and W.Z. contributed equally to this work and performed the experimental data. X.T.F., Y.Q.H. and Q.L.L. helped with data analysis and theoretical calculations. W.L.W., J.J.G. and D.Z. performed the FDTD simulations. W.L.W., W.Z. and D.Z. contributed to the writing of the manuscript.the volatilization of PBthe volatilization of MRDataset


Wilkins to the medical field. He is often referred to as the “Father of Pediatric Endocrinology.” Indeed, he came to the field of Pediatrics at a time when it was subdivided into specialties. He and his textbook “The Diagnosis and Treatment of Endocrine Disorders in Childhood and Adolescence” In 1935, Dr. Edwards Park, chief of Pediatrics at the Harriett Lane Home had the wisdom to foresee that the new discipline of endocrinology might be of value in understanding the growth and development of children; He showed even greater wisdom by asking Wilkins to organize a pediatric endocrine clinic. Wilkins resisted: “Do you want to make a charlatan out of me?”Nevertheless, Wilkins accepted the challenge and spent every evening into the small hours reading the fat tomes written by so-called “experts” in the field. Wilkins became increasingly frustrated by the absence of any science and the long convoluted descriptions of endless “glandular syndromes.” Lawson was never one to suffer fools gladly, and his most important act one night while reading in bed was to fling the volume against the wall while cursing the stuffed shirts who could write such garbage.He decided to begin over from scratch and learn everything he could by carefully documenting every clinical feature of his patients, and exploiting every opportunity to learn about mechanisms. Wilkins had little knowledge of statistics, but had a penetrating eye for what each of his patients could teach him. He had long ago adopting the practice of plotting all of his patients’ findings graphically as a function of time in the hope that such graphs might provide correlations and insights that might otherwise be missed.Lacking centile growth charts as we now know them, Lawson adopted the 1932 charts of Engelbach which gave average values for age of height, weight, span, segmental proportions, and circumferences of the head, chest, and abdomen. He adopted these charts because they permitted correlations of body proportions with growth parameters.He also laboriously traced out the appearance of epiphyses in the wrist, elbow, shoulder, knee, and ankle and developed his own scheme for determining bone age long before Greulich’s Atlas based on wrist x-rays.He started by studying hypothyroidism, plotting the effect of thyroid substitution treatment and its withdrawal on parameters of growth and development. His 1938 paper [Wilkins recognized, however, that to understand the physiological effects of thyroid and other hormones, he had to turn to the laboratory, a task for which he was ill-prepared. But he was a good judge of talent and had the good fortune to meet Walter Fleischmann, a refugee Viennese physiologist. When the Journal of Clinical Endocrinology made its debut in 1941, the first 2 papers in each of the first 2 issues were by Wilkins and Fleischmann reporting their studies in hypothyroidism. Since there were no methods available to measure thyroid hormone levels directly, he measured the effects of thyroid on lowering the elevated cholesterol in hypothyroid children and raising the depressed levels of creatine in the urine. He found these measures far more reliable than measurements of basal metabolic rate.It should come as no surprise, therefore, to learn that Wilkins had one of the first binary counters in Baltimore to study thyroid problems with radioactive iodine uptake studies, and one of the first to order the new protein bound iodine measurements on his patients.In 1944, Wilkins went through a period of despondency following the tragic death of his only son. He was rescued by Dr. Park, who induced him to become a full time member of the Johns Hopkins Department of Pediatrics.st International Congress of Pediatrics in Zurich in 1950.Wilkins brought with him his vast collection of case histories and photographs. He presented this extensive collection in a gigantic poster at the 1He then collated this material into the first Textbook of Pediatric Endocrinology. This launched, his fame spread rapidly, and students from the US and many foreign countries flocked to study under him. His textbook was considered the “Bible” of the field at the time.Wilkins was particularly challenged by difficulties encountered by patients with congenital adrenal hyperplasia. He knew that the secretions of adrenal androgens were controlled by ACTH and he made several unsuccessful attempts to suppress ACTH secretion by administering biologically weak androgens. When cortisone became available for experimental use, Wilkins immediately saw it as a more likely participant in the ACTH feedback mechanism, and in short order was able to show that the secretion of adrenal androgens in girls with CAH could be inhibited by the administration of a glucocorticoid hormone. Bartter Wilkins thought that the identification of steroid precursors in the urine of patients with CAH might reveal to us the biosynthetic pathways of human adrenal steroid biogenesis. Most steroid biochemists, however, were preoccupied with perfusing bovine adrenals with radio-labeled precursors and could not be bothered by clinical problems. Eventually he enlisted Dr. Seymour Lieberman in this endeavor and Lieberman accepted Wilkins’s prospective research associate, Dr. Alfred Bongiovanni, into his laboratory to learn advanced steroid methodology. As Wilkins had predicted, the studies of Bongiovanni led to the definition of the crucial enzymatic lesions in the different forms of adrenal hyperplasia. Al pioneered the pregnantriol method for monitoring adrenal suppression, and contributed greatly to our knowledge of the enzymatic defects in the several forms of CAH. Al and Walter Eberlein described and identified the defect in 11β-hydroxylase deficiency.Another early interest of Wilkins was sexual development. He was particularly intrigued by the syndrome of short stature, sexual infantilism, and multiple congenital anomalies in girls. This syndrome was not uncommon, and Henry Turner’s description had previously been described by a number of other authors. In 1942, 2 groups, Varney, Kenyon, and Koch in Chicago and Albright and his coworkers in Boston, reported that these girls had elevated urinary gonadotropins, thus demonstrating that their sexual infantilism was due to primary gonadal failure rather than hypopituitarism as had been suggested by Henry Turner in 1938. To learn more about their gonadal failure Wilkins persuaded Richard Te Linde, the chief of gynecology to explore the pelvis in 5 such patients.He found that the gonads in all patients consisted only of fibrous streaks composed exclusively of ovarian stromal cells.There were no germ cells or ovarian follicles, although there were occasional mesonephric remnants.In his classic 1944 paper, Wilkins reported his findings and pointed out that studies of patients with streak gonads might provide powerful evidence supporting or refuting the various theories of sex differentiation. He critically evaluated each of the theories that had been advanced, including that of Weisner who believed that in the absence of fetal gonadal secretions all embryos would be feminine, although androgen could influence male differentiation.The classic studies of Jost on the fetal castration in rabbits are very well known now. They demonstrated that the fetal testis is necessary for differentiation as a male, but in the absence of fetal gonads both the internal and external genitalia developed as a normal female. In 1949, Jost presented his findings on sex differentiation to an International Congress of Gynecology in Mexico City. On the way home, he arranged to visit the Carnegie Institute of Embryology in Baltimore which housed Streeter and Corner, the leading human embryologists of the day. After hearing Jost’s story, the embryologists insisted that he meet Dr. Wilkins who had a healthy interest in the hormonal control of sex differentiation.Twenty-five years later, Jost recalled the encounter:“He was 55 and I was 33 and not even a doctor of medicine. He calmly and patiently followed my description of the rabbit experiments and asked many penetrating questions. He then showed me his portfolio of clinical cases of sexual ambiguity asking me to help him interpret the pathophysiology. The discussions went on for many hours into the late afternoon and Dr. Wilkins finally concluded, “I am convinced that if what you say is true, half of my beautiful girls with ovarian agenesis are really boys!”Unfortunately there was no way to determine genetic sex at that time. Nevertheless, Wilkins felt sufficiently secure with this interpretation that he cited this hypothesis as a footnote in his 1950 textbook.Four or five years after Lawson’s encounter with Alfred Jost, when Mel Grumbach and I were fellows of Wilkins, we reported in journal club that a Canadian pathologist, named Murray Barr had discovered a cytological marker in nuclei of female cells but not in male cells. Lawson immediately phone Murray Barr and arranged for him to analyze skin biopsies from a group of our patients with what we then called ovarian agenesis.In 1954, we reported that 6 of 8 patients lacked the chromatin dot and presumably were “genetic XY males.”In the 1960s, Malcolm Ferguson-Smith and Barbara Migeon did the karyotypes of the patients showing that most of them had only one X-chromosome.Wilkins later modified his nomenclature to include various forms of the syndrome under the umbrella designation, “Syndrome of Gonadal Dysgenesis.” He stoutly maintained, however, that this syndrome should never have been designated “Turner Syndrome.”In his 1950 textbook, Wilkins described another kind of sexual ambiguity. She was an attractive 30 year old woman who had never menstruated and who lacked sexual hair. Surgical exploration of her pelvis revealed absence of uterus, but presence of testes and rudiments of epididymis and vas deferens.Her urinary 17 ketosteroids ranged between 15 and 20 mg/24 hr and her androgens measured by bioassay were similarly high for a female but normal for a male.Wilkins treated her with methyl testosterone, up to 50 mg/day with no discernable effect on seborrhea, sexual hair, or clitoral enlargement. He therefore postulated that all of her findings were due to resistance to androgen action at the peripheral level. He called these patients “hairless ladies with testes.” Several other patients were followed later. Their karyotypes were shown to be 46 XY with a plasma testosterone level usually above normal male range. The locus of the gene for the androgen receptor was determined by Drs. Meyer W, Migeon B, and Migeon C.  The geneThe name of testicular feminization was changed to androgen insensitivity syndrome by Money J and Migeon C.Unfortunately, Wilkins’s observation including the correct pathophysiology of the syndrome, published in 1950 in his textbook, was ignored and the disorder was called Swyer’s Syndrome for a while.Wilkins made many other seminal contributions to Pediatric Endocrinology during the short time that he was engaged in a full time academic career. Perhaps his single contribution that brought the nascent field of Pediatric Endocrinology into prominence was his poster session at the Sixth International Congress of Pediatrics in Zurich in 1950. This extensive display provided examples of each of the now common endocrine disorders in Pediatrics along with a delineation of diagnostic criteria and pathophysiologic basis, insofar as it was then known. This display was the foundation of his text, Disorders of Endocrine Secretions in Childhood and Adolescence.(13) Many European pediatricians came to Baltimore to study under Wilkins and on returning home, they founded the European Society of Pediatric Endocrinology (ESPE). Although the number of American postdoctoral fellows was not large, they and their fellows have made a very large impact on the development of Pediatric Endocrinology in America. Robert Blizzard and Claude Migeon, who succeeded Wilkins as codirectors of Pediatric Endocrinology at Harriett Lane honored their former chief by establishing an annual symposium in his name, and this symposium evolved into the Lawson Wilkins Pediatric Endocrine Society (LWPES).th birthday!The legacy left by Wilkins to the discipline of Pediatric Endocrinology is indeed remarkable for an individual who remained in the private practice of Pediatrics until well after his 50I have often wondered whether Wilkins should be included in the pantheon of great scientists. The word science comes from the Greek work “SCIO” which means “to know.” Wilkins’s major tool was insatiable curiosity – he could not stand not knowing. His curiosity led to great things, and I do not hesitate to classify him amongst the great scientists of all time.”Table Dr. Wilkins was not only one of the major creators of the new field of Pediatric Endocrinology but he was also a major mentor of trainees of this field.Dr. Melvin Grumbach from the University of California in San Francisco analyzed in a sensitive statement what made Dr. Wilkins a great man. He stated the following:“Lawson was a man for all seasons, a many sided man, clinician, scientist, mentor, educator, encyclopedist, recorder, raconteur, and a pioneer who fathered and fostered the academic and clinical discipline of Pediatric Endocrinology. He cast a large shadow.Lawson had a restless, inquiring mind, and insatiable curiosity. He was a great clinician but he was also a great scientist – not a bench scientist but a clinical investigator whose laboratory was the clinic, bedside, and operating room. Soon after founding the Endocrine Clinic at Harriet Lane Home, he recruited a series of gifted laboratory directors. They were able to bring to bear the most recent advances in laboratory techniques on the research questions at hand and served as laboratory mentors for a covey of fledgling fellows. Lawson had a profound understanding of the scientific method and the rules of evidence. A keen observer, with an extraordinary ordered mind, meticulous data collector and recorder, he instilled in all of us the importance of attention to detail whether in clinical observations or laboratory work.Lawson was a hypothesis tester and a critical one. To convince him of the validity of a clinical or laboratory findings or the evidence in favor of particular speculation, one had to do more than one’s homework. A born doubter, his acceptance did not come easily. Parenthetically, he gave little credence to idle speculation or ideas, hypotheses, or notions that were not susceptible to testing.Once Lawson developed an interest in a clinical problem, he explored it with great determination, commitment, and thought. He had a contagious enthusiasm and the ability to interest others skilled in the laboratory to address clinical problems. He read widely, and freely discussed the clinical issues that interested him with a wide and diverse group of scientists and clinical investigators. He was eminently approachable.A compassionate man with a lust for life, he was intensely loyal to his fellows, “The Boys,” and took great pride in their achievements. Lawson was an indefatigable worker, but he also loved a good time. Conviviality, get-togethers usually marked by song, and weekends on the Chesapeake were an important part of his and Lu’s life. He was a wonderful informal host. Lawson hated to be alone and thrived on gregariousness.Who can forget the twinkle in his eyes, the gentle smile, the glowing cigarette held between nicotine-stained fingers, the stentorian resonant voice, his warmth and vigor and the affection which he generated in his fellows?”Dr. Robert Blizzard, another fellow, wrote a profile of Lawson Wilkins in the Journal of Pediatrics. He had aThe Diagnosis and Treatment of Endocrine Disorders in Childhood and Adolescence. His book excelled as a model teaching text because of the clarity of the writing and the case histories which were frequently longitudinal.“Wilkins’ accomplishments as a teacher reached their pinnacle after he joined the faculty at Hopkins in 1946. He taught orally at the bedside, in the clinic, and in the classroom and through the written word in his manuscripts. He documented, through photography and charts, the longitudinal manifestations of endocrine, metabolic, and dysmorphologic diseases; this led to “poster teaching sessions” at the American Academy of Pediatrics annual meetings in the late 1940s and early 1950s. Because of the favorable reception, he published this material in the first edition (1950) of his textbook entitled, The memorable Saturday endocrinology clinics were held in the Harriet Lane Home outpatient department from 9:00am to 1:00pm and were attended by many residents, faculty members, fellows, and students. After the patients were all seen by a fellow or resident, the presentations and discussions began. As Wilkins paced back and forth across the floor in his white coat, with hands behind his back, he discussed what was known about each patient, what was known about the patient’s condition, and what was not known. As should be true of all great teachers, he welcomed thoughts, questions and comments.”The following listing of the many fellows of Lawson Wilkins and specific comments about these fellows was written in collaboration by William Cleveland and Claude Migeon. Efforts were made to be accurate but we apologize for any error or omission.Walter Fleischmann, Ph.D. (1938-1946) was born and educated in Vienna. His father Carl was an obstetrician, a friend of Sigmund Freud, and he delivered Anne Freud. Walter was a Ph.D. involved in research. In 1938, he was at a conference in Chicago at the time of the Munich Agreement. He was advised to stay in the United States and Lawson Wilkins gave him a job at Johns Hopkins University.Walter was able to bring his wife and daughter, Ruth, to the US after going to Antwerp. His parents and siblings went to England when they settled. Ruth Fleischmann Weiner wrote, “In effect, Lawson Wilkins saved the lives of the Fleischmann family.”Walter worked on the effects of various androgenic steroids on creatine metabolism in humans. He was also involved in the attempt to suppress adrenal hypersecretion by various synthetic steroids, unfortunately with effect until cortisone was used. He joined the Veteran Administration Hospital of Baltimore and, later worked in Tennessee.Roger Lewis, M.D. (1946-1950) was involved with the clinic collaborating with colleagues who carried out several studies of thyroid function and started the treatment of children with congenital adrenal hyperplasia.Eugenia Rosemberg, M.D. (1948-1950) came from Argentina and worked with Roger Lewis and Robert Klein, helping the investigation of the patients with congenital adrenal hyperplasia. When she left, she went to the NIH and later joined the steroid group in Shrewsbury, Massachusetts with Dr. Gregory Pincus. Dr. Gregory Pincus and Dr. M.C. Chang were the first to synthesize the combined oral contraceptive pill. Later, Eugenia established her Pediatric Endocrine Clinic at the Worchester Hospital.Salvatore de Majo, M.D. (1948-1950) graduated from medical school in Buenos Aires. He came to learn at the clinic and the treatment of its patients. In addition, he worked with Dr. Lewis on the effects of ovariectomy on albino rats, as well as on the effects of various synthetic steroids on the rat adrenals. When he returned home, he became the director of the Pediatric Endocrine Clinic at the Hospital de Niños in Buenos Aires.Robert Z. Klein, M.D. (1948-1950) graduated from the Harvard Medical School and had training in Pediatrics at the Boston Children’s Hospital. He was an instructor at Johns Hopkins working in Endocrinology with Wilkins and was co-author of some of the pioneering publications about adrenal hyperplasia. He left Hopkins for the University of Pittsburgh where he established a highly regarded program in Endocrinology, continuing research and training fellows. He subsequently held professorships at Boston University and Dartmouth. He continued to make valuable contributions particularly in the area of measuring outcome in congenital hypothyroidism and its relationship to treatment. In this work, he directed the New England Congenital Hypothyroidism Collective.Lytt Gardner, M.D. (1950-1952) was originally from North Carolina and could make the best julep in the world. He directed the laboratories at Hopkins and contributed to the work on congenital adrenal hyperplasia. He established a pediatric endocrine program at the new State University of New York Upstate Medical Center in Syracuse where he remained until his death in 1986. He was succeeded by Dr. Robert A. Richman. Dr. Gardner’s life, professional career, and many valuable contributions have been described by Dr. Mary L. Voorhees (former fellow), and includes a notable list of pediatric endocrinologists trained by Gardner. His work resulted in a highly respected textbook, Endocrine and Genetic Diseases of Childhood and Adolescence.John F. Crigler, Jr., M.D. (1950-1951) was a member of the house staff at Johns Hopkins. Prior to joining the Wilkins group, he was co-author of many of the early papers on treatment of adrenal hyperplasia with cortisone. He then went to Boston Children’s Hospital as a member of the faculty of the Harvard Medical School. He established a very productive endocrinology division. His training program included 70 fellows from all over the world. John remained in this position until his retirement.Claude J. Migeon, M.D. (1950-1952) completed his medical education and pediatric residency in Paris, France. A Fulbright Fellowship brought him to Lawson Wilkins for two years. After three very productive years with Leo T. Samuels in Salt Lake City studying cortisol secretion and metabolism in humans, he returned to Johns Hopkins, and stayed there for the rest of his long career. In 1960, he was named the Co-Director of the Pediatric Endocrine Clinic with Robert Blizzard and was named Director in 1974 until 1994. During these 30 years, he had many fellows from the US and abroad.John Money, Ph.D. (1951) led a group studying the psychologic factors involved in pediatric endocrine disorders. Other valuable contributions to this group came from the John and Joan Hampson. When John Money was asked how he came to Johns Hopkins, he responded as follows:“In 1949-1950, as a graduate student at Harvard, I had a student appointment at Massachusetts General Hospital, writing a dissertation on the psychosexuality of hermaphroditism. Fuller Albright and Fred Bartter arranged for me to meet Lawson Wilkins when he attended the American Academy of Pediatrics Annual Meeting in Boston and gave his popular workshop on the adrenogenital syndrome of female pseudohermaphroditism. The efficacy of cortisone, newly synthesized for the treatment of the syndrome was simultaneously confirmed at MGH and Johns Hopkins in the first week of 1950.Lawson and I got along well professionally, perhaps because I had already resolved to use pediatric not psychoanalytic English. He approved my request to visit Hopkins to abstract psychological information from the files of patients whose cases had been published by hospital number, and to interview maybe one or two of them for my dissertation. When the written letter of invitation arrived however, it was to invite me to work in the pediatric endocrine clinic full-time. I began in July 1951.It has always seemed remarkable to me that this very pragmatic, chart-making man, not much given to psychologizing, should have had the prescience to recognize that he was on to something basically very important psychologically in treating people with hormones.Although I was not a postdoctoral fellow in Pediatric Endocrinology, Lawson Wilkins provided me, especially at the famed Saturday clinic, with as much Pediatric Endocrinology as I needed to become the first pediatric psychoendocrinologist. Here resides the outstanding feature of his intellectual and academic grandeur as it most personally affected me.I think that Lawson Wilkins metaphorically adopted all of his trainees, his “boys” , as substitutes for his only son whom he lost at age 16 in a postal truck auto accident. Double-twisting the helix, he had also himself become a stand in for his son, starting a new career as if on his son’s behalf. Confronting his loss, he gave up general pediatrics and became a full time pediatric endocrinologist. In a sense, he was on an equal footing with his fellows as one of us, not an overbearing father, but a Socratic teacher.”Sam Silverman, M.D. (1951-1952) was interested only in clinical studies. He got involved with the special form of congenital adrenal hyperplasia, the hypertensive form and the salt-losing form. He also studied “Precocious Adrenarche.” He left Baltimore to go into practice at Pediatric Endocrinology in New Jersey.Alfred M. Bongiovanni, M.D. (1952-1955) and Walter Eberlein, M.D. (1952-1953) became well known for their contributions to the study of abnormal secretion of adrenal steroids in the various forms of congenital adrenal hyperplasia. They returned to Philadelphia to establish a Division of Pediatric Endocrinology. Eventually, Dr. Bongiovanni became Professor and Chairman at the Department of Pediatrics at the University of Pennsylvania from 1963 to 1972. Following this, he became an itinerant professor holding posts at the University of Ife, Nigeria, Cairo, and the Catholic University of Ponce-de-Leon in Puerto Rico. He later became Dean of this school. He then returned to the faculty of the University of Pennsylvania in 1980 where he remained until his death in 1984.George W. Clayton, M.D. (1952-1954) helped Dr. Bongiovanni as shown by a series of publications. Clayton returned to his beloved Texas where he established a program at Baylor College of Medicine in Houston. He was Professor of Pediatrics and director of the Endocrine Division until his retirement. He moved to Galveston and his principal activities relate to fishing, traveling, and his ongoing interest in the history of the Civil War.Melvin M. Grumbach, M.D. (1953-1955) was busy and very productive. He made a team with Dr. Judson Van Wyk, so their publications were conjoint. The main contributions were related to the study of sex chromosomes in ovarian agenesis and a genetic study of congenital adrenal hyperplasia with Dr. Barton Childs.He left Baltimore to head a division of Pediatric Endocrinology at Babies Hospital in New York. Among the many fellows he trained, one of the most outstanding was Selna Kaplan. When Dr. Grumbach moved to a position at the University of California at San Francisco, Selna went with him. An outstanding Division has flourished as a result of their efforts. Many leading endocrinologists have been trained in their program.Mel became chairman of the Department of Pediatrics at UCSF until his retirement. Distinguished colleagues have included Selna, Felix Conte, and Walter L. Miller.Judson J. Van Wyk, M.D. (1953-1955) was one of Wilkins’s most devoted disciples. Jud was involved with Grumbach and Bongiovanni in lab work during his fellowship. He left for the University of North Carolina, where he started a vigorous Clinic of Pediatric Endocrinology. His colleagues at UNC included Frank French, Joseph D’Ercole, and more recently Louis Underwood who assumed direction of the Division. Dr. Van Wyk trained many fellows including Dr. Stockholm. He made many important contributions, particularly in his work relating to somatomedin (IGF-1) as a growth factor.Thomas H. Shepard, M.D. (1954-1955) moved to Seattle after completion of a year with Wilkins where he was appointed to the faculty at the University of Washington. He directed a division of Pediatric Endocrinology at the Children’s Orthopedic Hospital from 1956-1961. He developed an interest in embryology and teratology; studies in this area became the main focus of his career. After a year as a research associate in embryology in the Department of Anatomy, University of Florida College of Medicine, he spent another 6 months in the Fetal Laboratory, University of Copenhagen with Dr. Henning Anderson.Upon his return to Seattle, he continued his academic career and headed a Birth Defects Research Laboratory for 30 years. He became Emeritus Professor in 1993. He published extensively – some reports involving Endocrinology but most related to embryology and teratology.Robert M. Blizzard, M.D. (1955-1957) was destined to play a major role in the Harriet Lane program and in Pediatric Endocrinology. After his training, he left Hopkins to direct a division at Ohio State in Columbus. Upon Wilkins’s retirement in 1960, Bob was chosen to succeed him as Clinical Director of the Harriet Lane Program with Claude Migeon as Laboratory Director. He was asked to serve as acting Chairman of the Department of Pediatrics at Hopkins following the departure of Dr. Robert Cooke. He did this for 15 months until the position was taken over by Dr. Littlefield.Later, Bob was recruited to the Chairmanship of the Department of Pediatrics at the University of Virginia in Charlottesville, a position which he held until his retirement. During his tenure as chairman, he maintained a productive career in Endocrinology, working with outstanding colleagues including Alan Rogol and Anne Johanson. In his “retirement,” he remains very productive with many roles including chairmanship of the Board of the Genentech Foundation.Gerald H. Holman, M.D. (1956-1958) became a peripatetic professor after completing his residency and fellowship at Hopkins. He spent 1958-1961 in Saskatoon and 1961-1964 in Kansas City. From 1964-1969, he was Professor and Chairman at the Medical College of Georgia. From 1969-1974, he was Professor and Head of Pediatrics at the University of Calgary. From 1974-1975, he was Professor and Chairman at Eastern Virginia School of Medicine. From 1975-1979, he was Dean at Norfolk. He then went to Amarillo, Texas and held various administrative and faculty positions there, including directing a division of Pediatric Endocrinology. In these various situations, he participated in a prestigious number of programs and committees. His publications are expectedly wide ranging including Endocrinology, nutrition, ethics, and the social aspects of medical care.Robert Stempfel, M.D. (1956-1958) went from the training program to appointment in the Department of Pediatrics, Duke University, School of Medicine as director of Pediatric Endocrinology. He maintained a clinical and laboratory program until his recruitment to the Chairmanship of Pediatrics at the newly established University of California School of Medicine at Davis. His involvement in Endocrinology there was somewhat peripheral. He recruited Dr. Bagher Sheikholislam to his faculty; Bagher continues in the program there. In 1971, Stempfel was enticed to come to Miami as Director of the Mailman Center for Child Development, Professor of Pediatrics and Associate Chairman. He maintained this position until 1995. During his tenure he became heavily involved in the political aspects of child care in the State of Florida and represented the School of Medicine, University of Miami, in Tallahassee in legislative matters. After giving up directorship of the Center he moved from Miami to Key Largo and maintained his political representation until 1995 when he retired completely. He wasable to devote his full attention to his abiding interest in fishing in the Keys and the Bahamas.Orville C. Green, M.D. (1957-1960) left Baltimore to establish a program at the Children’s Memorial Hospital in the Department of Pediatrics, School of Medicine, Northwestern University. He maintained a flourishing Division, productive both in research and training until his retirement. He currently spends winters in Sarasota and summers in Wilmette and Nantucket. Among his trainees was Dr. Robert Winters who has succeeded Orville in the direction of the Division. When asked about Lawson Wilkins, Orville recalled two statements made by Wilkins:1. “Never take money from a drug company – take their products for experimentation if they seem worthwhile but never take money – they will never get off your back.”2. “The clinical use of the science of endocrinology is to diagnose and treat conditions of excess and deficiency.” Orville adds, “I think this basic principle should be reaffirmed.”Gloria Steward, M.D. (1957) left the program after 6 months.David H. Mosier Jr., M.D. (1955-1957) was from Kansas. He went to the University of Notre Dame and Johns Hopkins Medical School. After a Pediatric Residency at the University of Southern California, he came back to Hopkins as a fellow in Pediatric Endocrinology with Wilkins. Afterwards, he returned to California, where he was named Professor of Pediatrics at the University of California, Irvine. As head of the Division of Endocrinology, he has been active in experimental and clinical research of the various problems influencing growth.David W. Smith, M.D. (1955-1956) spent two years in the United States Army after completing his residency in Pediatrics. He returned after two years to complete one year of fellowship with Wilkins in Endocrinology. He then spent a year in practice in Los Gatos, California before accepting a faculty appointment at the University of Wisconsin. He established an Endocrinology training program producing third generation fellows including Dr. Arlan Rosenbloom. He then took a sabbatical in Zurich and became interested in genetics. Like his mentor, he then proceeded to pioneer a new field, dysmorphology, and published the definitive text on the subject: “Recognizable Patterns of Human Malformation” which has continued as the authoritative compendium of dysmorphic syndromes. In 1966, he moved to the University of Washington where he remained as Professor of Pediatrics until his untimely death at the age of 55 years. His character and contributions are described in an introduction to a Festschrift issue of the Journal of Pediatrics in 1982.William W. Cleveland, M.D. (1958-1961) left the position of Assistant Professor at the University of Miami to come to Johns Hopkins as fellow with Lawson Wilkins. He worked diligently with patients and wrote several papers. William was also a close friend; he and his wife were our witnesses at my marriage to Barbara in 1960.Cleveland returned to his faculty position at the fledgling School of Medicine, University of Miami. He continued to direct a Division of Endocrinology for the ensuing 36 years. During twenty of those years (1969-1989), he was also Chairman of the rapidly expanding Department of Pediatrics.Malcolm M. Martin, M.D. (1958-1959) was originally from England. He helped review the question of pituitary dwarfism. He then went to Georgetown University in Washington D.C. where he directed the endocrine clinic.Raphael David, M.D. (1958-1962) was educated in the French system of Cairo. He migrated to the United States and was a Hopkins pediatric resident before joining the clinic of Lawson Wilkins. At the time of Wilkins’s first heart attack, Ralph was his constant companion in the Marburg Building. With time, they grew very friendly.Ralph has devoted his career to an excellent Division of Endocrinology in the Department of Pediatrics at the School of Medicine at New York University. His program has been highly productive in training and research. As might be expected from his urbane nature, he is a confirmed and enthusiastic New Yorker.David Alexander, M.D. (1958-1960) was originally from Scotland. He did his pediatric residency at Johns Hopkins. After residency, he joined the Pediatric Endocrine Clinic. Following one year of clinical work, he went with his Scottish countryman Dr. Malcolm Ferguson-Smith in cytogenetics. Malcolm was an expert in the investigation of karyotypes in patients. Another notable accomplishment during training of David was to marry Jean, another Hopkins pediatric resident. They moved to Kingston, Ontario from Baltimore where they have maintained practices, David in Endocrinology and Jean in child development.Cesar Bergada, M.D. (1959-1961) and his wife Estela came from prominent families in Buenos Aires. Cesar worked with Dr. Salvador de Majo and Dr. Martin Cullen. Cesar and Estela met Lawson when Lawson and his family visited South America in 1957. As a fellow, Cesar was involved in the study of DSD (intersex) patients in collaboration with Dr. Howard Jones in GynecologyUpon completion of his training in Baltimore, Cesar returned to Buenos Aires to establish an endocrine division at the Hospital de Niños R. Gutierrez, which he directed for more than three decades. Cesar was recognized as one of the outstanding pediatric endocrinologists in South America. He has trained many endocrinologists, including his own son and Marco Rivarola.Thomas Aceto Jr., M.D. (1960-1962) left the army in 1960 to join the training program at Hopkins, along with Alvro Camacho and Fritz Kenny. After that, he went to the Children’s Hospital of University of Buffalo. Then he became the Chairman of Pediatrics at the University of South Dakota at Sioux Falls. His next promotion was as Medical Director of the Cardinal Glennon Memorial Hospital at St. Louis University. Unfortunately, Thomas developed Alzheimer’s disease and died in 2009.Frederic M. Kenny, M.D. (1960-1962) graduated from Princeton. He attended Hopkins for medical school and pediatric resident training. He married Jean, a colleague in resident training. For two years (1958-1960) he was Pediatrician in Chief at the U.S. Naval Hospital in Annapolis.In 1960, he returned to Hopkins for two very busy years in Pediatric Endocrinology. Next, he moved to the Children’s Hospital at the University of Pittsburgh. There, he took the place of Dr. Robert Klein and worked at a very large diabetic clinic, which attracted other Hopkins fellows, Dr. Alan Drash and Dr. Dorothy Becker. Unfortunately, Fritz battled with depression and ended his own life in 1978.Wellington Hung, M.D. (1960-1962) did most of his training and spent most of his life in Washington D.C. at American University, the Medical School of George Washington University, and the Children’s Hospital of D.C.After two years at Hopkins doing clinical research, he returned to Children’s Hospital, National Medical Center, Washington D.C.During his stay at Hopkins, he had learned about thyroidology from Dr. Robert Blizzard, and he became an expert in this field.Along with colleagues Dr. August and Dr. Glasgow, he wrote a succinct book of Pediatric Endocrinology.Dagfinn Aarskog, M.D. (1962-1963) did his undergraduate and medical school studies in Norway at the University of Oslo and Bergen, respectively. He did his pediatric training at the University of Bergen prior to coming to Baltimore. Upon his return to Norway, he became Professor and Chairman of the University of Bergen in 1971. In 1984, he was Dean of the Faculty of Medicine. Dagfinn contributed greatly to the field of Pediatric Endocrinology, including describing the Aarskog Syndrome.John Spaulding, M.D. (1962-1963) was a fellow for only one year during which he contributed to the study of patients with the rare problem of unresponsiveness of the adrenals to ACTH. After his fellowship, he rejoined the University of Kansas Medical Center where he directed the clinic of Pediatric Endocrinology.JoAnne Brasel, M.D. (1962-1965) was a lovely lady who lived her life fighting a slow progressive, disabling neurological problem. She went to medical school at the University of Colorado and did her residency at Cornell University.From 1962 to 1965, she joined the Hopkins Pediatric Endocrinology program and joined the staff in 1968. She became interested in growth and development research, working successively at Cornell, Columbia, and Harbor-UCLA Medical Center. She was in charge of the training program at Harbor-UCLA. When she died in 2007, we lost a great scientist and a wonderful friend.Jordan Finkelstein, M.D. (1961-1963) spent two years at Hopkins. He worked with Dr. Kowarski on the determination of aldosterone secretion in rats in various conditions. Particularly, the study of patients with congenital adrenal hyperplasia showed that all of them have a salt-losing tendency, but those who had a milder mutation of their 21-hydroxylase gene could compensate with increased aldosterone secretion, therefore avoiding salt-loss. In contrast, the patients with severe mutations could not compensate and were salt-losers. Jordan returned to Montefiore Hospital in the Bronx.A. Avinoam Kowarski, M.D. (1962-1965) was born in Tel Aviv, Israel. He started medical school in Lausanne, Switzerland and finished at the Hebrew University of Jerusalem. After three years as fellow at Hopkins and two years at Hadassah University Hospital, he returned to the pediatric endocrine clinic, where he was involved with laboratory research. In 1981, he opened the Pediatric Endocrine Clinic at the University of Maryland.Gordon Kennedy, M.D. (1951-1952) came from Cambridge, England, with the purpose to see the function of the Pediatric Endocrine Clinic. He was an expert on experimental brain lesions to rats which resulted in increased appetite and gross obesity.José Cara, M.D. (1951-1952) came from Argentina. He was interested in clinical work and eventually joined Lytt Gardner at Syracuse. José’s son was also an endocrinologist.Dr. Jean Bertrand (1955-1956) from Lyon, France. We became close friends and after his return home, he went to join me in Stockholm to help me at the Karolinska Hospital where we worked with Dr. Carl Gemzell on the transplacental passage of steroids. Bernadette Loras, M.D. (1962-1964), Maguelone Forest, M.D., and José Saez, M.D. were three pupils of Jean Bertrand who worked in his laboratories.Other doctors from abroad were truly involved in all the activities of the Clinic. The first was Raphael Rappaport, M.D. (1960-1961) came from the Hopital de Enfants Malades and then returned home to create an important clinic. Paul Malvaux, M.D. (1961-1962) came from Louvain and similarly returned to his institution to be the Director of Pediatric Endocrinology. Both of them returned to Johns Hopkins to help with the clinical load when Dr. Blizzard was temporary Chief of Pediatrics.Andrea Prader of Zurich, Switzerland, the founder of the European Society of Pediatric Endocrinology, wrote the following:Some doctors who had not been fellows felt that Wilkins was their mentor. For example, “Because Lawson had the greatest impact on my training as a clinician and clinical investigator, I add a personal note regarding Lawson. He, along with Guido Fanconi, stimulated my interests in endocrinology, metabolism, genetics, and growth. Both were superb clinicians and forceful and enthusiastic teachers.Their scientific contributions were not the results of systematic laboratory research in the framework of a sophisticated research program, but the offshoots of very careful clinical observations combined with a deep interest in the patient and his problems. They used charts to follow the courses of diseases and the growth of patients. They recognized important disease aspects not noted by others, were able to add new insights into many diseases, and offered challenging new speculations.”This was the same for Henning Anderson of Denmark. Henning had a special relationship with Lawson. When they were together, Lawson and Henning considered themselves as Vikings and Harold the Blue Tooth was one of their ancestors.Another important admirer of Lawson Wilkins was Professor Alfred Jost, head of the Laboratory of Comparative Physiology, Faculty of Sciences at the University of Paris. After Wilkins’s death in 1963, Dr. Jost gave the fourth Lawson Wilkins Memorial Lecture on April 26, 1971. On that occasion, he wrote about meeting Lawson Wilkins:“On my return from Mexico, I visited several eminent American experts in the field on sex differentiation in animals. The first stop was in Baltimore, where I was to meet world-famous scientists at the Department of Biology of The Johns Hopkins University and at the Department of Embryology of the Carnegie Institution of Washington. Dr. Robert K. Burns an Associate in Embryology was very friendly to me during this visit, and he suggested that I should meet at The Johns Hopkins Hospital a clinician by the name of Dr. Lawson Wilkins, who was interested in problems of human genital anomalies. Dr. Burns made the appointment for the early afternoon, and thus I was introduced to Lawson Wilkins. He was 55, I was 33; he was a well-known clinician, I was not even a doctor of medicine. He calmly and patiently followed my description of the rabbit experiments, looking at the rabbit pictures, asked many pertinent questions, and listened to the interpretations proposed for human anomalies. Then he submitted me to a keen clinical examination. I had to comment on the illustrations and reports concerning clinical cases. I thus had the privilege of being among the very first ones who saw the cases later to appear in the first edition of “The Diagnosis and Treatment of Endocrine Disorders in Childhood and Adolescence.” But not only did I have to look at pictures, I was asked for interpretations which were coldly evaluated and screened. Also, I was introduced to extremely important clinical experiments, for instance, those concerning the absence of sensitivity to androgens of “hairless women with testes.”Constantine Papadatos, M.D. (1955) from Athens, Greece, Edouard Juillard, M.D. (1955) from Lausanne, Switzerland, John Gerrard, M.D. (1956) and Donald Delahaye, M.D. (1956) from Canada, Fouad Hamaoui, M.D. (1956) from Beirut, Lebanon, Jean-Luc de Gennes, M.D. (1957) from Paris, France, Enrico Delanto, M.D. (1959) from Mexico, Marija Nikesic, M.D. (1960) from Belgrade, Yugoslavia, John Eckert, M.D. (1961) from Australia, and Morato Marano, M.D. (1962) from Montevideo, Uruguay.Several of the fellows from abroad attended the daily clinics of Lawson Wilkins, including A bibliography can be found in Additional file nd of December, I discovered that I was 80 years old. I was amazed and a little afraid. It had been 50 years since Dr. Wilkins died. I wrote a little note; a copy of which follows:In 2003, on the 22How is it possible? Already eighty? Pas Possible! So many years. But what can I do if it is true? Resign myself to it hope for another day and be thankful for my past youthNow in 2013, we are ten years later and I am 90 years old Figure . What haIt is of interest to consider what role “chance” plays for better or worse in life. In 1950, in Paris when I got my MD degree, I was not ready for settling down: get married, open an office of pediatrics, probably in Reims and be a respectful citizen.Chance permitted me to apply for a Fulbright Fellowship to go to a hospital in Chicago and see my good friends Bill and Stella Nanos. Instead, chance had it that Dr. Wilkins asked for me at Hopkins. At the end of the two year fellowship, Dr. Wilkins made it possible for me to continue working in Salt Lake City. And after 3 years in Utah, he brought me back to Baltimore for the rest of my life.I want to conclude this memoir in thanking with all of my heart, Dr. Wilkins, for permitting me to have a wonderful life, with my wife Barbara, my children Jacques, Jean-Paul, and Nicole; my many fellows who were like children; my kind colleagues, and all of my good friends.The author has no competing interests to disclose.bibliographyClick here for file


After the publication of this work  it was nThese authors have now been added to the list, and the updated author contributions are included below.VP, LHV, KNN, JP and TL carried out ex vivo/in vitro experiments. RM and KRJ carried out in vivo malaria experiments under the supervision of OB and AH. VP, AP, VS, GK, GD, XZ, SW and MK performed data analysis. AP and MN carried out the mathematical modelling. DFR and WRH developed mouse model used in the study. AM provided mice and expertise on their use. WZ and JK carried out T-cell live imaging under the supervision of PC. VP, MN and SAT wrote the manuscript with contributions from all authors. SAT and MN supervised the work. All authors read and approved the final manuscript.The authors declare that they have no competing interests.