bluuebunny/crossref_metadata_2025 huggingface dataset:
Prolonged or recurrent acute seizures after pediatric arterial ischemic stroke are associated with increasing epilepsy risk
Authors: Fox Christine K , Mackay Mark T , Dowling Michael M , Pergami Paola , Titomanlio Luigi , Deveber Gabrielle ,   the SIPS Investigators
Published: July 2016

Aim

To determine epilepsy risk factors after pediatric stroke.

Method

A cohort of children with arterial ischemic stroke (birth–18y) was enrolled at 21 centers and followed for 1 year. Acute seizures (≤7d after stroke) and active epilepsy (at least one unprovoked remote seizure plus maintenance anticonvulsant at 1y) were identified. Predictors were determined using logistic regression.

Results

Among 114 patients (28 neonates and 86 children) enrolled, 26 neonates (93%) and 32 children (37%) had an acute seizure. Acute seizures lasted longer than 5 minutes in 23 patients (40%) and were frequently recurrent: 33 (57%) had 2 to 10 seizures and 11 (19%) had more than 10. Among 109 patients with 1‐year follow‐up, 11 (10%) had active epilepsy. For each year younger, active epilepsy was 20% more likely (odds ratio [OR] 0.8, 95% confidence interval [CI] 0.6–0.99, p=0.041). Prolonged or recurrent acute seizures also increased epilepsy risk. Each additional 10 minutes of the longest acute seizure increased epilepsy risk fivefold (OR 4.7, 95% CI 1.7–13). Patients with more than 10 acute seizures had a 30‐fold increased epilepsy risk (OR 30, 95% CI 2.9–305).

Interpretation

Pediatric stroke survivors, especially younger children, have a high risk of epilepsy 1 year after stroke. Prolonged or recurrent acute seizures increase epilepsy risk in a dose‐dependent manner.
Timing matters: open‐loop stimulation does not improve overnight consolidation of word pairs in humans
Authors: Weigenand Arne , Mölle Matthias , Werner Friederike , Martinetz Thomas , Marshall Lisa
Published: July 2016

The application of auditory clicks during non‐rapid eye movement (NREM) sleep phase‐locked to the up state of the slow oscillation (closed‐loop stimulation) has previously been shown to enhance the consolidation of declarative memories. We designed and applied sequences of three clicks during deep NREM sleep to achieve a quasi‐phase‐dependent open‐loop stimulation. This stimulation was successful in eliciting slow oscillation power in the stimulation period. Although fast and slow spindle power were markedly decreased during the stimulation period, memory consolidation did not differ from control. During putative up states fast spindle power remained, however, at control levels. We conclude that concurrence of slow oscillations and fast spindles suffices to maintain memory consolidation at control levels despite an overall decreased spindle activity.
Melanopsin supports irradiance‐driven changes in maintained activity in the superior colliculus of the mouse
Authors: Dasilva Miguel , Storchi Riccardo , Davis Katherine E. , Grieve Kenneth L. , Lucas Robert J.
Published: July 2016

Melanopsin phototransduction allows intrinsically photosensitive retinal ganglion cells (ipRGCs) to maintain firing under sustained illumination and to encode irradiance. ipRGCs project to different parts of the visual system, including the superficial superior colliculus (sSC), but to date there is no description of melanopsin contributions to the activity of that nucleus. We sought to fill that gap using extracellular recordings to describe light response in the sSC. We failed to observe light responses in the sSC of mice lacking rod and cone function, in which melanopsin provides the only photoreception. Nor did the sSC of intact animals track very gradual ramps in irradiance, a stimulus encoded by melanopsin for other brain regions. However, in visually intact mice we did find maintained responses to extended light steps (30 s) and to an irradiance ramp upon which a high frequency (20 Hz) temporal white noise was superimposed. Both of these responses were deficient when the spectral composition of the stimulus was changed to selectively reduce its effective irradiance for melanopsin. Such maintained activity was also impaired in mice lacking melanopsin, and this effect was specific, as responses of this genotype to higher spatiotemporal frequency stimuli were normal. We conclude that ipRGCs contribute to irradiance‐dependent modulations in maintained activity in the sSC, but that this effect is less robust than for other brain regions receiving ipRGC input.
Functional consequences of experience‐dependent plasticity on tactile perception following perceptual learning
Authors: Trzcinski Natalie K. , Gomez‐Ramirez Manuel , Hsiao Steven S.
Published: July 2016

Continuous training enhances perceptual discrimination and promotes neural changes in areas encoding the experienced stimuli. This type of experience‐dependent plasticity has been demonstrated in several sensory and motor systems. Particularly, non‐human primates trained to detect consecutive tactile bar indentations across multiple digits showed expanded excitatory receptive fields (RFs) in somatosensory cortex. However, the perceptual implications of these anatomical changes remain undetermined. Here, we trained human participants for 9 days on a tactile task that promoted expansion of multi‐digit RFs. Participants were required to detect consecutive indentations of bar stimuli spanning multiple digits. Throughout the training regime we tracked participants’ discrimination thresholds on spatial (grating orientation) and temporal tasks on the trained and untrained hands in separate sessions. We hypothesized that training on the multi‐digit task would decrease perceptual thresholds on tasks that require stimulus processing across multiple digits, while also increasing thresholds on tasks requiring discrimination on single digits. We observed an increase in orientation thresholds on a single digit. Importantly, this effect was selective for the stimulus orientation and hand used during multi‐digit training. We also found that temporal acuity between digits improved across trained digits, suggesting that discriminating the temporal order of multi‐digit stimuli can transfer to temporal discrimination of other tactile stimuli. These results suggest that experience‐dependent plasticity following perceptual learning improves and interferes with tactile abilities in manners predictive of the task and stimulus features used during training.
An integrative in silico system for predicting dysregulated genes in the human epileptic focus: Application to SLC transporters
Authors: Mirza Nasir , Vasieva Olga , Appleton Richard , Burn Sasha , Carr Daniel , Crooks Daniel , du Plessis Daniel , Duncan Roderick , Farah Jibril Osman , Josan Vivek , Miyajima Fabio , Mohanraj Rajiv , Shukralla Arif , Sills Graeme J. , Marson Anthony G. , Pirmohamed Munir
Published: July 2016

Objective

Many different gene families are currently being investigated for their potential role in epilepsy and in the response to antiepileptic drugs. A common research challenge is identifying the members of a gene family that are most significantly dysregulated within the human epileptic focus, before taking them forward for resource‐intensive functional studies. Published data about transcriptomic changes within the human epileptic focus remains incomplete. A need exists for an accurate in silico system for the prediction of dysregulated genes within the epileptic focus. We present such a bioinformatic system. We demonstrate the validity of our approach by applying it to the solute carrier (SLC) gene family. There are >400 known SLCs. SLCs have never been systematically studied in epilepsy.

Methods

Using our in silico system, we predicted the SLCs likely to be dysregulated in the epileptic focus. We validated our in silico predictions by identifying ex vivo the SLCs dysregulated in epileptic foci, and determining the overlap between our in silico and ex vivo results. For the ex vivo analysis, we used a custom oligonucleotide microarray containing exon probes for all known SLCs to analyze 24 hippocampal samples obtained from surgery for pharmacoresistant mesial temporal lobe epilepsy and 24 hippocampal samples from normal postmortem controls.

Results

There was a highly significant (p < 9.99 × 10−7) overlap between the genes identified by our in silico and ex vivo strategies. The SLCs identified were either metal ion exchangers or neurotransmitter transporters, which are likely to play a part in epilepsy by influencing neuronal excitability.

Significance

The identified SLCs are most likely to mediate pharmacoresistance in epilepsy by enhancing the intrinsic severity of epilepsy, but further functional work will be needed to fully evaluate their role. Our successful in silico strategy can be adapted in order to prioritize genes relevant to epilepsy from other gene families.
Cryoconite pans on Snowball Earth: supraglacial oases for Cryogenian eukaryotes?
Authors: Hoffman P. F.
Published: July 2016

Geochemical, paleomagnetic, and geochronological data increasingly support the Snowball Earth hypothesis for Cryogenian glaciations. Yet, the fossil record reveals no clear‐cut evolutionary bottleneck. Climate models and the modern cryobiosphere offer insights on this paradox. Recent modeling implies that Snowball continents never lacked ice‐free areas. Wind‐blown dust from these areas plus volcanic ash were trapped by snow on ice sheets and sea ice. At a Snowball onset, sea ice was too thin to flow and ablative ice was too cold for dust retention. After a few millenia, sea ice reached 100 s of meters in thickness and began to flow as a ‘sea glacier’ toward an equatorial ablation zone. At first, dust advected to the ablative surface was recycled by winds, but as the surface warmed with rising CO2, dust aka cryoconite began to accumulate. As a sea glacier has no terminus, cryoconite saturated the surface. It absorbed solar radiation, supported cyanobacterial growth, and sank to an equilibrium depth forming holes and decameter‐scale pans of meltwater. As meltwater production rose, drainages developed, connecting pans to moulins, where meltwater was flushed into the subglacial ocean. Flushing cleansed the surface, creating a stabilizing feedback. If the dust flux rose, cryoconite was removed; if the dust flux waned, cryoconite accumulated. In addition to cyanobacteria, modern cryoconite holes are inhabited by green algae, fungi, protists, and certain metazoans. On Snowball Earth, cryoconite pans provided stable interconnected habitats for eukaryotes tolerant of fresh to brackish cold water on an ablation surface 60 million km2 in area. Flushing and burial of organic matter was a potential source of atmospheric oxygen. Dominance of green algae among Ediacaran eukaryotic primary producers is a possible legacy of Cryogenian cryoconite pans, but a schizohaline ocean—supraglacial freshwater and subglacial brine—may have exerted selective stress on early metazoans, or impeded their evolution.
A new model of the formation of Pennsylvanian iron carbonate concretions hosting exceptional soft‐bodied fossils in Mazon Creek, Illinois
Authors: Cotroneo S. , Schiffbauer J. D. , McCoy V. E. , Wortmann U. G. , Darroch S. A. F. , Peng Y. , Laflamme M.
Published: July 2016

Preservation of Pennsylvanian‐aged (307 Ma) soft‐bodied fossils from Mazon Creek, Illinois, USA, is attributed to the formation of siderite concretions, which encapsulate the remains of terrestrial, freshwater, and marine flora and fauna. The narrow range of positive δ34S values from pyrite in individual concretions suggests microenvironmentally limited ambient sulfate, which may have been rapidly exhausted by sulfate‐reducing bacteria. Tissue of the decaying carcass was rapidly encased by early diagenetic pyrite and siderite produced within the sulfate reduction and methanogenic zones of the sediment, with continuation of the latter resulting in concretion cementation. Cross‐sectional isotopic analyses (δ13C and δ18O) and mineralogical characterization of the concretions point to initiation of preservation in high porosity proto‐concretions during the early phases of microbially induced decay. The proto‐concretion was cemented prior to compaction of the sediments by siderite as a result of methanogenic production of 13C‐rich bicarbonate—which varies both between Essex and Braidwood concretions and between fossiliferous and unfossiliferous concretions. This work provides the first detailed geochemical study of the Mazon Creek siderite concretions and identifies the range of conditions allowing for exceptional soft‐tissue fossil formation as seen at Mazon Creek.
Mapping marginal croplands suitable for cellulosic feedstock crops in the Great Plains, United States
Authors: Gu Yingxin , Wylie Bruce K.
Published: July 2016

Growing cellulosic feedstock crops (e.g., switchgrass) for biofuel is more environmentally sustainable than corn‐based ethanol. Specifically, this practice can reduce soil erosion and water quality impairment from pesticides and fertilizer, improve ecosystem services and sustainability (e.g., serve as carbon sinks), and minimize impacts on global food supplies. The main goal of this study was to identify high‐risk marginal croplands that are potentially suitable for growing cellulosic feedstock crops (e.g., switchgrass) in the US Great Plains (GP). Satellite‐derived growing season Normalized Difference Vegetation Index, a switchgrass biomass productivity map obtained from a previous study, US Geological Survey (USGS) irrigation and crop masks, and US Department of Agriculture (USDA) crop indemnity maps for the GP were used in this study. Our hypothesis was that croplands with relatively low crop yield but high productivity potential for switchgrass may be suitable for converting to switchgrass. Areas with relatively low crop indemnity (crop indemnity <$2 157 068) were excluded from the suitable areas based on low probability of crop failures. Results show that approximately 650 000 ha of marginal croplands in the GP are potentially suitable for switchgrass development. The total estimated switchgrass biomass productivity gain from these suitable areas is about 5.9 million metric tons. Switchgrass can be cultivated in either lowland or upland regions in the GP depending on the local soil and environmental conditions. This study improves our understanding of ecosystem services and the sustainability of cropland systems in the GP. Results from this study provide useful information to land managers for making informed decisions regarding switchgrass development in the GP.
Determination of Platinum‐Group Elements and Gold in Ferromanganese Nodule Reference Samples
Authors: Berezhnaya Evgeniya D. , Dubinin Alexander V.
Published: July 2016

A measurement procedure for determining of Ru, Pd, Ir, Pt and Au mass fractions in ferromanganese deposits by inductively coupled plasma‐mass spectrometry after acid digestion and anion exchange preconcentration is presented. To eliminate incomplete recovery after sorption preconcentration of the platinum‐group elements (PGE) and Au, a standard addition method was used. Detection limits ranged from 0.02 ng (Pd, Ir) to 0.19 ng (Ru). The measurement results for ferromanganese nodule reference material NOD‐A‐1 and NOD‐P‐1 agree with earlier reported values. Intermediate precision of PGE concentration data for nodule reference materials in this work was 5–24% (1s) and could reflect sample heterogeneity.
International Trends in Health Science Librarianship Part 20: The Balkan States (Serbia and Slovenia)
Authors: Ivkovic Ana , Rožić Anamarija , Turk Nana
Published: July 2016

This is the 20th in a series of articles exploring international trends in health science librarianship in the 21st century. The focus of the present issue is the Balkan region (Serbia and Slovenia). The next regular feature will look at Russia and the Ukraine.

JM
Development of quality measurement instruments for root canal treatment
Authors: Eliyas S. , Briggs P. F. A. , Harris I. R. , Newton J. T. , Gallagher J. E.
Published: July 2016

Aim

To devise measurement instruments for ‘quality’ of root canal treatment to assess training and outcome of general dental practitioners working within primary care settings.

Method

Scoring systems relating to quality of root canal treatment were developed using expert consensus and published literature. Domains scored included the Treatment Process, Quality of the Obturation, Clinical Healing, Radiographic Healing and Tooth Complexity. Scoring systems were applied to 10 clinical cases treated by each dentist at the beginning and 10 cases treated at the end of their clinical training and 135 cases treated after completion of training. The dentists recorded the treatment process and clinical healing in clinical logs. Two examiners independently scored the radiographs after undertaking calibration and training. Inter‐ and intra‐examiner reliability of scoring radiographic outcomes was tested using Cohen's Kappa statistics.

Results

An instrument was created with four domains to assess quality (two for process and two for outcome of root canal treatment), and a measure of case complexity. Domains of treatment process (n = 240 teeth), outcome (n = 32 teeth) and complexity (n = 215 teeth) were scored using radiographs. The Kappa scores for intra‐examiner reliability between 0.22 and 1, whilst inter‐examiner reliability ranged between 0.18 and 0.99.

Conclusion

Evidence‐based scores for assessment of the quality (process and outcome) and complexity (structure) of root canal treatment were devised. They were reliable, provided that clinicians were trained in record keeping and examiners have in depth training and calibration in the use of the instruments.
Phytochemicals content, antioxidant and hypoglycaemic activities of commercial nutmeg mace (Myristica fragrans L.) and pimento (Pimenta dioica (L.) Merr.)
Authors: Loizzo Monica Rosa , Sicari Vincenzo , Tenuta Maria Concetta , Leporini Maria Rosaria , Falco Tiziana , Pellicanò Teresa Maria , Menichini Francesco , Tundis Rosa
Published: July 2016

Commercially dried powder of nutmeg mace (Myristica fragrans) and pimento (Pimenta dioica) spices was investigated for their high performance liquid chromatography phenolic profile and their antioxidant and hypoglycaemic properties by α‐amylase and α‐glucosidase inhibition tests. Generally, mace showed the most promising activity. An interesting protection of lipid peroxidation with an IC50 value of 7.7 μg mL−1 was found. A significant result was also obtained in ferric reducing ability power assay if compared to the positive control butylated hydroxytoluene (IC50 value of 68.7 μg mL−1 vs. 63.2 μg mL−1, respectively). Mace also exhibited the highest carbohydrate‐hydrolysing enzyme inhibitory activity with IC50 values of 62.1 and 75.7 μg mL−1 against α‐amylase and α‐glucosidase, respectively. Overall, these results support the use of these spices not only as flavouring agent but also as food preservative and functional ingredients.
Effects of sodium tripolyphosphate on functional properties of low‐salt single‐step high‐pressure processed chicken breast sausage
Authors: Xue Siwen , Zou Yufeng , Chen Xing , Yang Huijuan , Xing Tong , Xu Xinglian , Zhou Guanghong
Published: July 2016

Influences of sodium tripolyphosphate (STPP) contents (0.1, 0.2, 0.3 and 0.4%) on water holding capacity (WHC) and texture properties of low‐salt (1.2% NaCl) single‐step high‐pressure processed chicken breast sausages (LSSS‐HPP sausages) were evaluated. Results showed that WHC was improved (4–5%) by the addition of STPP. However, the STPP contents customarily used for cooked sausages (0.3–0.5%) were excessive for LSSS‐HPP sausages, causing a soft and tacky texture. Sausages containing 0.1% of STPP had the best taste according to the sensory evaluations. Chemical interactions plus Raman spectroscopic analysis revealed that STPP addition partly changed native structures of myofibrillar proteins. Furthermore, higher STPP contents in the meat batter prevented those proteins from high pressure denaturing and aggregating in the subsequent single‐step HPP procedure. Increased hydrogen bonds and decreased hydrophobic interactions explained the better WHC and softer texture. Therefore, 0.1% of STPP is the optimal content in the processing of new‐type LSSS‐HPP sausages.
M2 polarization of murine peritoneal macrophages induces regulatory cytokine production and suppresses T‐cell proliferation
Authors: Oishi Shinji , Takano Ryosuke , Tamura Satoshi , Tani Shinya , Iwaizumi Moriya , Hamaya Yasushi , Takagaki Kosuke , Nagata Toshi , Seto Shintaro , Horii Toshinobu , Osawa Satoshi , Furuta Takahisa , Miyajima Hiroaki , Sugimoto Ken
Published: July 2016

Bone‐marrow‐derived macrophages are divided into two phenotypically and functionally distinct subsets, M1 and M2 macrophages. Recently, it was shown that adoptive transfer of M2‐polarized peritoneal macrophages reduced the severity of experimental colitis in mice. However, it is still unclear whether peritoneal macrophages possess the same ability to be polarized to cells with functionally different phenotypes and cytokine production patterns as bone‐marrow‐derived macrophages. To address this question, we examined the ability of peritoneal macrophages to be polarized to the M1 and M2 phenotypes and determined the specific cytokine profiles of cells with each phenotype. We showed that peritoneal macrophages, as well as bone‐marrow‐derived macrophages, were differentiated into M1 and M2 phenotypes following stimulation with interferon‐γ (IFN‐γ) and interleukin‐4 (IL‐4)/IL‐13, respectively. Following in vitro stimulation with lipopolysaccharide, M2‐polarized peritoneal macrophages predominantly expressed T helper type 2 (Th2) cytokines and regulatory cytokines, including IL‐4, IL‐13, transforming growth factor‐β and IL‐10, whereas M1‐polarized peritoneal macrophages expressed negligible amounts of Th1 and pro‐inflammatory cytokines. ELISA showed that M2‐polarized peritoneal macrophages produced significantly more IL‐10 than M1‐polarized peritoneal macrophages. Notably, M2‐polarized peritoneal macrophages contributed more to the suppression of T‐cell proliferation than did M1‐polarized peritoneal macrophages. The mRNA expression of Th2 cytokines, including IL‐4 and IL‐13, increased in T‐cells co‐cultured with M2‐polarized macrophages. Hence, our findings showed that M2 polarization of peritoneal macrophages induced regulatory cytokine production and suppressed T‐cell proliferation in vitro, and that resident peritoneal macrophages could be used as a new adoptive transfer therapy for autoimmune/inflammatory diseases after polarization to the regulatory phenotype ex vivo.
Brachial‐ankle pulse wave velocity, but not ankle‐brachial index, predicts all‐cause mortality in patients with diabetes after lower extremity amputation
Authors: Ikura Kazuki , Hanai Ko , Oka Seiji , Watanabe Makiko , Oda Yuri , Hamada Mariko , Kato Yuka , Shinjyo Takamichi , Uchigata Yasuko
Published: July 2016

We examined whether brachial‐ankle pulse wave velocity (baPWV) and ankle‐brachial pressure index (ABI) are predictors for mortality in diabetic patients after lower extremity amputation. This was an observational historical cohort study of 102 Japanese diabetic patients after first non‐traumatic lower extremity amputation, with a mean age of 63 years (standard deviation 12 years). The end‐point was all‐cause mortality. During the mean follow‐up period of 3.3 years, 44 patients reached the end‐point. In both univariate and multivariate analyses, baPWV (m/s) (hazard ratio [HR] 1.05 and 1.04, both P < 0.01, respectively), but not ABI (HR 0.38 and 0.89, P = 0.08 and 0.86, respectively), was a significant predictor for the end‐point. When baPWV (above or below the median [21.8 m/s]) and ABI (normal [0.9–1.4] or not) were analyzed as categorical variables, the results were similar. In conclusion, baPWV, but not ABI, might be a predictor for all‐cause mortality in diabetic patients after lower extremity amputation.
Glucagonoma syndrome: a review and update on treatment
Authors: John A.M. , Schwartz R.A.
Published: July 2016

Glucagonoma syndrome is defined by the presence of an alpha‐cell secreting tumour of the pancreas, elevated levels of glucagon, and a characteristic rash called necrolytic migratory erythema (NME). NME is usually a specific and often initial finding of glucagonoma syndrome, but it may occur in other settings unassociated with an alpha‐cell pancreatic tumour (pseudoglucagonoma syndrome). Glucagonoma syndrome must be distinguished from pseudoglucagonoma syndrome. Prompt recognition of NME and subsequent workup for a glucagonoma can allow for an earlier diagnosis and enhance the chances of a favourable outcome. In particular, metastases occur late, so early recognition of glucagonoma syndrome before liver metastases can be life‐saving. Surgical resection is the definitive treatment for glucagonoma syndrome, although chemotherapeutic agents, somatostatin analogues and radionuclide therapy are also employed. Herein, we offer an approach to workup after identifying NME and an update on its current treatment modalities.
Non‐cosmetic dermatological uses of botulinum neurotoxin
Authors: Forbat E. , Ali F.R. , Al‐Niaimi F.
Published: July 2016

Botulinum neurotoxin (BoNT) is renowned for its inhibitory effects on the neuromuscular junction. The evidence for its use in cosmetic dermatology and in non‐dermatological indications is well established. We have systemically analysed the evidence for the non‐cosmetic dermatological uses of BoNT. This review presents the many small studies showing promising results for the use of BoNT in a multitude of dermatological diseases, including (but not limited to) hyperhidrosis, Darier's disease, Hailey–Hailey disease, pompholyx and hidradenitis suppurativa. There is, however, the need for larger, double‐blinded randomized control trials against established treatments to cement the evidence base underlying the use of BoNT in dermatology.
The clinical spectrum of syphilitic balanitis of Follmann: report of five cases and a review of the literature
Authors: Mainetti C. , Scolari F. , Lautenschlager S.
Published: July 2016

Background

Eugène Follmann first described syphilitic balanitis as a manifestation of primary syphilis in 1948 and since then it has been known as syphilitic balanitis of Follmann (SBF). So far, SBF has rarely been described in literature.

Objectives

We are reporting five additional cases of SBF considering the broad differential diagnosis of balanitis.

Methods

A review of the available literature of SBF was performed and five additional cases analyzed.

Results

In our case series, the clinical appearance of SBF shows a heterogeneous spectrum varying from painful oedematous balanoposthitis with beginning paraphimosis to superficial erosive balanitis and even to painless induration of the glans.

Conclusions

SBF might be seen more frequently than has been described due to misinterpretation. Therefore primary syphilis should be included in the differential diagnosis of balanitis and balanoposthitis.
Atypical discrete papular lichen myxedematosus associated with monoclonal gammopathy: report of four cases and review of the literature
Authors: Hermans C. , Goldscheider I. , Ruzicka T. , Rongioletti F.
Published: July 2016

Background

Discrete papular lichen myxedematosus (DPLM) is a rare form of localized lichen myxedematosus that presents with skin involvement only and without systemic involvement.

Object

To describe our experience with atypical cases of DPLM associated with monoclonal gammopathy.

Methods

Data were collected from patients with clinicopathological evidence of DPLM associated with monoclonal gammopathy who presented to the Department of Dermatology of two tertiary university‐affiliated medical centres from 2000 to 2015 and were followed prospectively.

Results

The sample included four patients (three males) with a mean age of 58 years. No clinicopathological differences from typical cases of DPLM were observed, except for the presence of monoclonal gammopathy. The patients were followed up for a mean of 34 months (6–72 months) and no progression to scleromyxedema, multiple myeloma or systemic involvement was observed. No therapy was applied, except for topical tacrolimus or steroids, and the eruptions remained stable.

Conclusion

Our experience indicates an excellent prognosis of DPLM even for atypical cases in spite of the presence of monoclonal gammopathy.
Cold urticaria: a 20‐year follow‐up study
Authors: Jain S.V. , Mullins R.J.
Published: July 2016

Background

Chronic cold urticaria results in significant morbidity, yet information on its natural history is limited.

Objective

We examined the natural history of chronic cold urticaria and its impact on quality of life.

Methods

We analysed the characteristics of patients diagnosed with cold urticaria at a community‐based specialist allergy practice in the Australian Capital Territory (ACT) between 1995 and 2015. Follow‐up data were obtained using a mailed questionnaire. Possible predictive factors of disease severity and symptom duration were evaluated.

Results

A total of 99 patients were assessed with a median age of 42 (range 5–81 years); 63% were female and the median age of onset of symptoms was 22 years. Of 41 questionnaire responders (14 ± 10.9 years follow‐up; median 12 years), 5‐ and 10‐year resolution rates were 17.9% ± 6.2% and 24.5% ± 7.2%, respectively. Whereas 22% reported resolution and 23% described improvement, the remaining 55% reported stable or worsening disease. Most individuals relied on lifestyle modification to ameliorate symptoms rather than medication. Risk factors for persistent disease were intercurrent atopic disease (P = 0.025) and those with longer duration of symptoms at the time of initial assessment (P < 0.001). Secondary causes of cold urticaria were identified in only two patients, both with B‐cell malignancy.

Conclusion

In a subset of patients, cold urticaria has low rates of spontaneous resolution and results in lifestyle changes and impaired quality of life.
‘Multimorbidity’ as the manifestation of network disturbances
Authors: Sturmberg Joachim P. , Bennett Jeanette M. , Martin Carmel M. , Picard Martin
Published: July 2016

We argue that ‘multimorbidity’ is the manifestation of interconnected physiological network processes within an individual in his or her socio‐cultural environment. Networks include genomic, metabolomic, proteomic, neuroendocrine, immune and mitochondrial bioenergetic elements, as well as social, environmental and health care networks. Stress systems and other physiological mechanisms create feedback loops that integrate and regulate internal networks within the individual. Minor (e.g. daily hassles) and major (e.g. trauma) stressful life experiences perturb internal and social networks resulting in physiological instability with changes ranging from improved resilience to unhealthy adaptation and ‘clinical disease’. Understanding ‘multimorbidity’ as a complex adaptive systems response to biobehavioural and socio‐environmental networks is essential. Thus, designing integrative care delivery approaches that more adequately address the underlying disease processes as the manifestation of a state of physiological dysregulation is essential. This framework can shape care delivery approaches to meet the individual's care needs in the context of his or her underlying illness experience. It recognizes ‘multimorbidity’ and its symptoms as the end product of complex physiological processes, namely, stress activation and mitochondrial energetics, and suggests new opportunities for treatment and prevention. The future of ‘multimorbidity’ management might become much more discerning by combining the balancing of physiological dysregulation with targeted personalized biotechnology interventions such as small molecule therapeutics targeting specific cellular components of the stress response, with community‐embedded interventions that involve addressing psycho‐socio‐cultural impediments that would aim to strengthen personal/social resilience and enhance social capital.
Heterogeneity‐mediated cellular adaptation and its trade‐off: searching for the general principles of diseases
Authors: Heng Henry H.
Published: July 2016

Big‐data‐omics have promised the success of precision medicine. However, most common diseases belong to adaptive systems where the precision is all but difficult to achieve. In this commentary, I propose a heterogeneity‐mediated cellular adaptive model to search for the general model of diseases, which also illustrates why in most non‐infectious non‐Mendelian diseases the involvement of cellular evolution is less predictable when gene profiles are used. This synthesis is based on the following new observations/concepts: 1) the gene only codes “parts inheritance” while the genome codes “system inheritance” or the entire blueprint; 2) the nature of somatic genetic coding is fuzzy rather than precise, and genetic alterations are not just the results of genetic error but are in fact generated from internal adaptive mechanisms in response to environmental dynamics; 3) stress‐response is less specific within cellular evolutionary context when compared to known biochemical specificities; and 4) most medical interventions have their unavoidable uncertainties and often can function as negative harmful stresses as trade‐offs. The acknowledgment of diseases as adaptive systems calls for the action to integrate genome‐ (not simply individual gene‐) mediated cellular evolution into molecular medicine.
Combining machine learning and propensity score weighting to estimate causal effects in multivalued treatments
Authors: Linden Ariel , Yarnold Paul R
Published: July 2016

Rationale, aims and objectives

Interventions with multivalued treatments are common in medical and health research; examples include comparing the efficacy of competing interventions and contrasting various doses of a drug. In recent years, there has been growing interest in the development of methods that estimate multivalued treatment effects using observational data. This paper extends a previously described analytic framework for evaluating binary treatments to studies involving multivalued treatments utilizing a machine learning algorithm called optimal discriminant analysis (ODA).

Method

We describe the differences between regression‐based treatment effect estimators and effects estimated using the ODA framework. We then present an empirical example using data from an intervention including three study groups to compare corresponding effects.

Results

The regression‐based estimators produced statistically significant mean differences between the two intervention groups, and between one of the treatment groups and controls. In contrast, ODA was unable to discriminate between distributions of any of the three study groups.

Conclusions

Optimal discriminant analysis offers an appealing alternative to conventional regression‐based models for estimating effects in multivalued treatment studies because of its insensitivity to skewed data and use of accuracy measures applicable to all prognostic analyses. If these analytic approaches produce consistent treatment effect P values, this bolsters confidence in the validity of the results. If the approaches produce conflicting treatment effect P values, as they do in our empirical example, the investigator should consider the ODA‐derived estimates to be most robust, given that ODA uses permutation P values that require no distributional assumptions and are thus, always valid.
A low percentage of HER‐2 amplification whereas indicates poor prognosis in salivary carcinoma ex pleomorphic adenoma: a study of 140 cases
Authors: Xia Liang , Hu Yuhua , Li Jiang , Gu Ting , Zhang Chunye , Wang Lizhen , Tian Zhen
Published: July 2016

Background

Human epidermal growth factor receptor 2 (HER‐2) has been found in many malignant tumours including salivary malignancy. HER‐2‐targeted therapy has been applied in the treatment of HER‐2‐overexpressing carcinoma. The aim of this study was to determine the status of HER‐2 in salivary invasive carcinoma ex pleomorphic adenoma (ICXPA) in a relatively large Chinese sample, which may provide HER‐2‐targeted therapy with profound support in the future.

Methods and results

We collected 140 ICXPAs and their related clinicopathological and follow‐up data. All cases were examined for HER‐2 expression by immunohistochemistry and gene amplification by fluorescence in situ hybridization, if necessary. The study showed that the ratio of HER‐2 positivity was only 25% (35/140) in all cases, but the positive ratio in ICXPAs with luminal differentiation for malignant component (32/79, 40.5%) was much higher than that in cases with non‐luminal differentiation (3/61, 4.9%). The overexpression of HER‐2 was closely associated with gender, histological grade and N stage. HER‐2‐positive tumours conferred short overall survival time (P = 0.036) and short disease‐specific survival time (P = 0.042) in patients, but HER‐2 status was not an independent predictor of prognosis.

Conclusions

Human epidermal growth factor receptor 2 amplification is significantly associated with cell differentiation of the malignant component in ICXPA and it implies an unfavourable prognosis. Although HER‐2 positivity is not common in the tumour, HER‐2‐targeted therapy for those HER‐2‐positive patients is still worth expecting.
Diffusion MRI: literature review in salivary gland tumors
Authors: Attyé A , Troprès I , Rouchy R‐C , Righini C , Espinoza S , Kastler A , Krainik A
Published: July 2016

Surgical resection is currently the best treatment for salivary gland tumors. A reliable magnetic resonance imaging mapping, encompassing tumor grade, location, and extension may assist safe and effective tumor resection and provide better information for patients regarding potential risks and morbidity after surgical intervention. However, direct examination of the tumor grade and extension using conventional morphological MRI remains difficult, often requiring contrast media injection and complex algorithms on perfusion imaging to estimate the degree of malignancy. In addition, contrast‐enhanced MRI technique may be problematic due to the recently demonstrated gadolinium accumulation in the dentate nucleus of the cerebellum. Significant developments in magnetic resonance diffusion imaging, involving voxel‐based quantitative analysis through the measurement of the apparent diffusion coefficient, have enhanced our knowledge on the different histopathological salivary tumor grades. Other diffusion imaging‐derived techniques, including high‐order tractography models, have recently demonstrated their usefulness in assessing the facial nerve location in parotid tumor context. All of these imaging techniques do not require contrast media injection. Our review starts by outlining the physical basis of diffusion imaging, before discussing findings from diagnostic studies testing its usefulness in assessing salivary glands tumors with diffusion MRI.
Carbon source–sink limitations differ between two species with contrasting growth strategies
Authors: Burnett Angela C. , Rogers Alistair , Rees Mark , Osborne Colin P.
Published: July 2016

Understanding how carbon source and sink strengths limit plant growth is a critical knowledge gap that hinders efforts to maximize crop yield. We investigated how differences in growth rate arise from source–sink limitations, using a model system comparing a fast‐growing domesticated annual barley (Hordeum vulgare cv. NFC Tipple) with a slow‐growing wild perennial relative (Hordeum bulbosum). Source strength was manipulated by growing plants at sub‐ambient and elevated CO2 concentrations ([CO2]). Limitations on vegetative growth imposed by source and sink were diagnosed by measuring relative growth rate, developmental plasticity, photosynthesis and major carbon and nitrogen metabolite pools. Growth was sink limited in the annual but source limited in the perennial. RGR and carbon acquisition were higher in the annual, but photosynthesis responded weakly to elevated [CO2] indicating that source strength was near maximal at current [CO2]. In contrast, photosynthetic rate and sink development responded strongly to elevated [CO2] in the perennial, indicating significant source limitation. Sink limitation was avoided in the perennial by high sink plasticity: a marked increase in tillering and root:shoot ratio at elevated [CO2], and lower non‐structural carbohydrate accumulation. Alleviating sink limitation during vegetative development could be important for maximizing growth of elite cereals under future elevated [CO2].
Health‐related quality of life in Japanese children with acute lymphoblastic leukemia during and after chemotherapy
Authors: Kobayashi Kyoko , Nakagami‐Yamaguchi Etsuko , Hayakawa Akira , Adachi Souichi , Hara Junichi , Tokimasa Sadao , Ohta Hideaki , Hashii Yoshiko , Rikiishi Takeshi , Sawada Machiko , Kuriyama Kikuko , Kohdera Urara , Kamibeppu Kiyoko , Kawasaki Hirohide , Oda Megumi , Hori Hiroki
Published: July 2016

Background

Quality of life (QOL) as a treatment outcome has not yet been evaluated among patients receiving a specific treatment regimen by treatment phase in a consistent manner. This exploratory cross‐sectional study evaluated the QOL of children with acute lymphoblastic leukemia (ALL) receiving one of the most popular treatment regimens in Japan (Japan Association of Childhood Leukemia Study ALL‐02 revised protocol).

Methods

Children aged 5–18 years with newly diagnosed B‐cell precursor ALL were included. The Pediatric Quality of Life Inventory™ 4.0 Generic Core Scales (PedsQL‐J) were completed by children with ALL and their siblings, as well as by age‐ and sex‐matched healthy controls. PedsQL Cancer Module (PedsQL‐C) scores were also collected from children with ALL.

Results

QOL in children with ALL of the consolidation phase group was significantly decreased compared with that of healthy controls, except in the area of emotional functioning. Regarding the maintenance phase group, QOL impairment was noted in the physical and school functioning, but no differences were noted in social functioning. The off‐treatment group had a large effect size only for physical functioning, and the social functioning score was even better in children with ALL than in matched controls. QOL of children with ALL differed with treatment phase. Effect size varied with function and treatment phase.

Conclusions

QOL may change with the progression of treatment, and the timing of these changes varied according to function and problem.
Physical behaviour of Cretaceous calcareous nannofossil ooze: Insight from flume studies of disaggregated chalk
Authors: Buls Toms , Anderskouv Kresten , Friend Patrick L. , Thompson Charlotte E. L. , Stemmerik Lars
Published: July 2016

Geomorphic features such as drifts, sediment waves and channels have been documented in the Upper Cretaceous of north‐west Europe. These features are interpreted to result from bottom currents and have been used to refine chalk depositional models and quantify palaeocirculation patterns. Chalk was first deposited as calcareous nannofossil ooze and geomorphic features are the result of sediment reworking after deposition. There is limited knowledge on the processes that govern nannofossil ooze mobility, thus forcing uncertainty onto numerical models based on sedimentological observations. This article provides an extensive view of the erosional and depositional behaviour of calcareous nannofossil ooze based on experimental work using annular flumes. A fundamental observation of this study is the significant decrease of nannofossil ooze mobility with decreasing bed porosity. Erosion characteristics, labelled as erosion types, vary with total bed porosity (φ) and applied shear stress (τ0). High‐porosity ooze (φ >80%) is characterized by constant erosion rates (Em). At φ <77%, however, erosion characteristics showed greater variance. Surface erosion was typically followed by transitional erosion (with asymptotically decreasing Em), and stages of erosion with constant, and exponential erosion rates. The estimated erosion thresholds (τc) vary from ca 0·05 to 0·08 Pa for the onset of surface erosion and up to ca 0·19 Pa for the onset of constant erosion (φ of 60 to 85%). Variability of deposition thresholds (τcd) from ca 0·04 to 0·13 Pa reflects the influence of variable suspended sediment concentration and τ0 on settling particle size due to the identified potential for chalk ooze aggregation and flocculation. Additionally, deposition thresholds seem to be affected by the size of eroded aggregates whose size correlates with bed porosity. Lastly, slow sediment transport without resuspension occurred in high‐porosity ooze as surface creep, forming low‐relief sedimentary features resembling ripples. This process represents a previously undescribed mode of fine‐grained nannofossil ooze transport.
Investigations on sound energy decays and flows in a monumental mosque
Authors: Sü Gül Zühre , Xiang Ning , Çalışkan Mehmet
Published: July 2016

This work investigates the sound energy decays and flows in the Süleymaniye Mosque in İstanbul. This is a single-space superstructure having multiple domes. The study searches for the non-exponential sound energy decay characteristics. The effect of different material surfaces and volumetric contributions are investigated using acoustic simulations and in situ acoustical measurements. Sound energy decay rates are estimated by Bayesian decay analysis. The measured data reveal double- or triple-slope energy decay profiles within the superstructure. To shed light on the mechanism of energy exchanges resulting in multi-slope decay, spatial sound energy distributions and energy flow vectors are studied by diffusion equation model (DEM) simulations. The resulting sound energy flow vector maps highlight the contribution of a sound-reflective central dome contrasted with an absorptive carpeted floor in providing delayed energy feedback. In contrast, no multi-slope energy decay pattern is observed in DEM simulations with a bare marble floor, which generates a much more diffuse sound field than in the real situation with a carpeted floor. The results demonstrate that energy fragmentation, in support of the non-exponential energy decay profile, is due to both the sound absorption characteristics of materials and to their distributions, as well as to relations between the subvolumes of the mosque's interior.
Deriving disyllabic word variants from a Chinese conversational speech corpus
Authors: Liu Yi-Fen , Tseng Shu-Chuan , Jang Jyh-Shing Roger
Published: July 2016

Motivated by the quasi-categorical reduced forms of disyllabic words produced in Chinese conversational speech, a frequency-based selection procedure of typical pronunciation by disyllabic word type and reduction degree is proposed in this paper. This variant-selection algorithm utilizes techniques of free phone recognition and phonetic similarity score calculation to account for Chinese syllable structure. Four reduction types are suggested by considering the presence of a within-word syllable boundary: Citation form-like reduction, marginal segment deletion, nuclei merger, and syllable merger. The results show that the most frequent reduction types for disyllabic words in Chinese conversation are citation form-like reduction and syllable merger. In particular, high-frequency disyllabic words preferentially take the extreme syllable-merger form. As shown in the analysis, segmental reduction in Chinese disyllabic words is morphology-dependent. It is also related to the prosodic position at which a disyllabic word is produced as well as the temporal quality of the word. Finally, in the automatic speech recognition experiments, the performance was improved by adding a small number of variants selected by the algorithm to the pronunciation dictionary of the system.