bluuebunny/crossref_metadata_2025 huggingface dataset:
Impact of a family‐oriented rehabilitation programme on behavioural and emotional problems in healthy siblings of chronically ill children
Authors: Besier T. , Hölling H. , Schlack R. , West C. , Goldbeck L.
Published: March 2010

Objective  To evaluate the impact of a family‐oriented inpatient rehabilitation programme on behavioural and emotional problems in healthy siblings of chronically ill children and to assess the association between these problems and quality of life.

Methods  A total of 259 healthy children (4–16 years, M = 8.6 years, SD = 3.3) with a chronically ill sibling were enrolled in the study. Parents filled in the Strengths and Difficulties Questionnaire, while the children answered a self‐report quality of life instrument (LQ‐KID) at the time of admission and discharge from the clinic and at a 6‐month follow‐up. Comparisons were performed with a matched control group from the German general population (n= 777).

Results  Significant behavioural or emotional symptoms were found in 30.5% of the healthy siblings, the relative risk of having elevated scores being 2.2 compared with the control group. Symptoms were inversely correlated with quality of life (r=−0.42). During the inpatient rehabilitation, symptoms decreased significantly to a normal level. Similarly, quality of life significantly improved, except in the dimension family relations.

Conclusions  Family‐oriented inpatient rehabilitation is a promising approach to improve the mental health of children with a chronically ill sibling.
Natural history of subclinical hyperthyroidism in elderly patients with TSH between 0·1 and 0·4 mIU/l: a prospective study
Authors: Rosario Pedro Weslley
Published: March 2010

Context  One important aspect in the decision to treat or not elderly patients with subclinical hyperthyroidism (SCH) is the risk of progression to overt hyperthyroidism (OH).

Objective  To define the natural history of endogenous SCH in elderly patients with TSH between 0·1 and 0·4 mIU/l.

Design  Prospective study. One hundred and two women aged ≥60 years with persistently low TSH ranging from 0·1 to 0·4 mIU/l and normal free T4 and T3 were studied. Patients using L‐T4 or antithyroid drugs, previously treated for hyperthyroidism, with pituitary disease, using corticosteroids, amiodarone, dopaminergic agonists, with atrial fibrillation or heart disease were excluded. Seven patients had Graves’ disease, 91 had nodular disease and 4 presented no defined cause. The time of follow‐up ranged from 12 to 70 months (median 41 months).

Results  Three patients progressed to OH (elevated T4 and/or T3) and four other patients to persistently low TSH (<0·1 mIU/l) in the presence of increase in serum T3 when compared with baseline. These patients were treated. Twenty‐four women presented sustained normalization of TSH and none progressed to hypothyroidism. SCH with TSH in the 0·1–0·4 mIU/l range persisted in 71 patients, 4 of them (5·6%) being treated because of the development of atrial fibrillation or heart disease during follow‐up. The only independent predictor of progression of SCH was an initial TSH value <0·2 mIU/l.

Conclusions  In elderly patients with endogenous SCH and TSH between 0·1 and 0·4 mIU/l progression to clinical hyperthyroidism is uncommon (approximately 1% per year), spontaneous TSH normalization may occur, and persistence of SCH for many years is the most likely.
The tight relationship between papillary thyroid cancer, autoimmunity and inflammation: clinical and molecular studies
Authors: Muzza Marina , Degl’Innocenti Debora , Colombo Carla , Perrino Michela , Ravasi Elena , Rossi Stefania , Cirello Valentina , Beck‐Peccoz Paolo , Borrello Maria Grazia , Fugazzola Laura
Published: March 2010

Objective  The recent concept that oncogenes responsible for thyroid neoplastic transformation are able to elicit an inflammatory protumourigenic microenvironment raises interest in further studies on papillary thyroid cancer (PTC) associated with thyroid autoimmunity.

Patients  The clinical and molecular features, and the expression of inflammation‐related genes, were investigated in a large series of PTCs with and without associated thyroiditis (groups A, n = 128 and B, n = 215).

Results  The two groups did not show significant differences in clinical and prognostic features, whereas they harboured a significantly different genetic background (P = 0·001), with RET/PTC1 being more represented in PTCs associated with autoimmunity, and BRAFV600E in patients with PTC alone. A RET/PTC rearrangement was also found in 41% of non‐neoplastic thyroiditis tissues, contralateral to tumours harbouring either RET/PTC or BRAF mutations. The expression of genes encoding CCL20, CXCL8 and l‐selectin was significantly higher in PTC specimens (either with RET/PTC, BRAFV600E or unknown genetic lesion) compared with normal thyroid samples. On the contrary, thyroiditis showed l‐selectin expression levels even higher than PTCs, but CCL20 and CXCL8 levels comparable with normal tissues.

Conclusions  The present data extend the knowledge about the tight relationships among oncogenes, thyroiditis and thyroid cancer. A different genetic background among PTCs with and without associated autoimmunity has been firstly demonstrated. The strong association between RET/PTC1 and thyroiditis points to a critical role of this oncoprotein in the modulation of the autoimmune response. Moreover, preliminary expression studies, indicating enhanced expression of inflammatory molecules in PTCs, suggest a proinflammatory, nonautoimmune relationship between thyroiditis and thyroid cancer.
The pharmacodynamic equivalence of levothyroxine and liothyronine: a randomized, double blind, cross‐over study in thyroidectomized patients
Authors: Celi Francesco S. , Zemskova Marina , Linderman Joyce D. , Babar Nabeel I. , Skarulis Monica C. , Csako Gyorgy , Wesley Robert , Costello Rene , Penzak Scott R. , Pucino Frank
Published: March 2010

Context  The substitution of liothyronine (L‐T3) for levothyroxine (L‐T4) is commonly employed during thyroid hormone (TH) withdrawal in preparation for diagnostic and therapeutic interventions on thyroid cancer patients. Presently, only limited data are available on the L‐T3 for L‐T4 therapeutic substitution.

Objective  To characterize the pharmcodynamic equivalence of L‐T3 and L‐T4.

Design  Randomized, double‐blind, cross‐over intervention study.

Setting  NIH clinical center.

Patients  Ten thyroidectomized patients.

Interventions  Study participants were treated with L‐T3 or L‐T4 with a target TSH ≥ 0·5 ≤ 1·5 mU/l for at least 30 days before undergoing inpatient testing. Following testing, subjects crossed‐over according to the same scheme.

Main outcome measures  Area under the serum concentration–time curve of TSH from 0 to 60 min (AUC0–60) and peak TSH serum concentration (Cmax) following thyrotropin‐releasing hormone (TRH) stimulation test, total L‐T4 and L‐T3 dose (mcg/kg), and L‐T4/L‐T3 ratio.

Results  No difference was observed for time 0 TSH values between L‐T3 and L‐T4 replacement phases (1·48 ± 0·77 vs. 1·21 ± 0·62 mU/l, P = 0·293) at average daily doses of 40·3 ± 11·3 mcg L‐T3 and 115·2 ± 38·5 mcg L‐T4, L‐T3: L‐T4 ratio 0·36 ± 0·06. TRH stimulation test resulted in similar L‐T3 vs. L‐T4 TSH responses with AUC0–60 of 326·1 (95% CI 232·6–457·1) and 247·1 (95% CI 153·8–397·1) mU* min/l (P = 0·285); and Cmax of 6·83 (95% CI 4·88–9·55) and 5·23 (95% CI 3·31–8·3) mU/l (P = 0·383).

Conclusions  This is the first study addressing the equivalency between L‐T3 and L‐T4 therapy measured by baseline and TRH‐stimulated TSH. The therapeutic substitution of L‐T3 for L‐T4 was achieved at approximately 1:3 ratio.
d3‐Growth hormone receptor polymorphism in acromegaly: effects on metabolic phenotype
Authors: Montefusco Laura , Filopanti Marcello , Ronchi Cristina L. , Olgiati Luca , La‐Porta Carmen , Losa Marco , Epaminonda Paolo , Coletti Francesca , Beck‐Peccoz Paolo , Spada Anna , Lania Andrea G. , Arosio Maura
Published: March 2010

Objective  A common polymorphic variant of the growth hormone receptor (GHR) is because of genomic deletion of exon 3 and has been linked with increased responsiveness to exogenous GH. The impact of this polymorphism in acromegaly, a disease characterized by endogenous excess of GH and partial loss of IGF‐I feedback on tumoural GH secretion, is not clear. The aim of this study was to investigate possible influences of d3GHR on the GH/IGF‐I relationship and metabolic parameters in acromegaly.

Design and methods  Retrospective study on 76 acromegalic patients. Genotype analysis was carried out on leucocyte DNA by multiplex PCR assay. Clinical, hormonal and biochemical parameters at diagnosis were collected from patients’ medical records.

Results  Forty‐two patients (55·3%) were homozygotes for the allele encoding the full‐length GHR (fl/flGHR), 27 patients were heterozygotes (fl/d3) and seven homozygotes (d3/d3) for the genomic deletion of exon 3. Heterozygotes and homozygotes for the d3 allele were considered together (d3GHR) and compared with fl/flGHR patients. d3GHR and fl/flGHR patients showed no difference in GH and IGF‐I levels or in the relationship between these two parameters. Patients bearing d3GHR had a lower body mass index (BMI) than patients bearing fl/flGHR (25·8 ± 2·1 vs. 28·1 ± 4·8 kg/m2, P < 0·05). Diabetes mellitus and hypertension were equally distributed, but more d3GHR patients had a normal glucose tolerance (66·7%vs. 56·3%, P < 0·05). The presence of d3GHR allele, and not BMI or age, was a significant negative predictor of insulin levels 120 min after oral glucose load (β = −80·8, P < 0·05).

Conclusions  This study supports the hypothesis that the d3GHR is functionally different from the fl/fl variant mostly for the effects on body weight regulation and on glucose metabolism.
Expression of inflammatory molecules and associations with BMI in children
Authors: Dedoussis George V. Z. , Kapiri Alexandra , Samara Anastasia , Dimitriadis Dimitris , Lambert Daniel , Pfister Michele , Siest Gerard , Visvikis‐Siest Sophie
Published: March 2010

Eur J Clin Invest 2010; 40 (5): 388–392

Background  Adipose tissue secrets several adipokines that have been proposed to be enrolled in many inflammatory pathways. Our aim was to investigate the adipokine expression in adipose tissue and peripheral blood mononuclear cells (PBMCs) in children.

Materials and methods  Thirty‐one (17 males and 14 females) healthy children aged 10·9 ± 1·8 years with a body mass index (BMI) of 19·3 ± 3·5 kg m−2 were enrolled. Adipokines (TNF‐alpha, IL‐6 and leptin) gene expression was quantified by real‐time quantitative PCR in adipose tissue and PBMCs from the same children. Their serum levels were also measured.

Results  BMI was positively correlated with leptin gene expression in adipose tissue and with leptin serum levels (β = 0·476, P = 0·006 and β = 0·576, P = 0·003 respectively). Leptin’s serum levels were positively correlated with leptin gene expression in adipose tissue (β = 0·462, P = 0·02). Adipose tissue gene expression of leptin and TNF‐alpha and serum leptin and TNF‐alpha serum levels were positively correlated (β = 0·752, P < 0·001, β = 0·311 and P = 0·015 respectively). In PBMCs, a positive correlation between TNF‐alpha and IL‐6 expression was found (β = 0·526, P = 0·042).

Conclusion  We demonstrated powerful correlations of adipokines gene expression in adipose tissue and PBMCs in children, underlying that these molecules share common pathways related to childhood obesity.
Antiphospholipid syndrome: pathogenesis and a window of treatment opportunities in the future
Authors: Mehdi Ali A. , Uthman Imad , Khamashta Munther
Published: March 2010

Eur J Clin Invest 2010; 40 (5): 451–464

Background Antiphospholipid syndrome (APS) is a systemic autoimmune vascular disease characterized by recurrent thrombotic episodes and/or obstetric complications. Management of this disease has been restricted mainly to anticoagulation; however, in recent years, significant advancement has been made in elucidating the pathophysiology of the disease including antiphospholipid antibody (aPL)‐induced activation of the platelets, endothelial cells, monocytes, complement and coagulation cascade. Stemming from these advances, potential targeted therapeutic approaches have been proposed.

Materials and methods We utilized a computer‐assisted search of the literature (MEDLINE, National Library of Medicine, Bethesda, MD, USA) up until September 2009 using the keywords: antiphospholipid syndrome, antiphospholipid antibodies, anticardiolipin antibodies, lupus anticoagulant, anti beta‐2 glycoprotein antibodies, complement system, tissue factor, p38 mitogen‐activated protein kinase (p38 MAPK), nuclear factor kappa B, toll‐like receptors, annexin, Rituximab, statins and tumour necrosis factor.

Results Several study groups have separately demonstrated the importance of inflammatory mediators in the pathogenesis of APS. It was also established that tissue factor, MAPK, nuclear factors kappa B, and the complement system are integral to the disease process. Toll‐like receptors and annexin have as well been associated with the disease pathophysiology. Some study groups proposed new targeted therapeutic strategies some of which have shown promising results in preclinical studies. These include Rituximab, complement inhibition, anti‐cytokine therapy, p38 MAPK inhibitors, nuclear factor inhibitors and tissue factor inhibitors.

Conclusion As more insight is being gained into the pathophysiology of APS, newer therapeutic strategies are being proposed that might lead to safer and more efficacious treatment modalities in the future.
Spatial and temporal patterns of walleye pollock (Theragra chalcogramma) spawning in the eastern Bering Sea inferred from egg and larval distributions
Authors: BACHELER NATHAN M. , CIANNELLI LORENZO , BAILEY KEVIN M. , DUFFY‐ANDERSON JANET T.
Published: March 2010

Walleye pollock Theragra chalcogramma (pollock hereafter) is a key ecological and economic species in the eastern Bering Sea, yet detailed synthesis of the spatial and temporal patterns of pollock ichthyoplankton in this important region is lacking. This knowledge gap is particularly severe considering that egg and larval distribution are essential to reconstructing spawning locations and early life stages drift pathways. We used 19 yr of ichthyoplankton collections to determine the spatial and temporal patterns of egg and larval distribution. Generalized additive models (GAMs) identified two primary temporal pulses of pollock eggs, the first occurring from 20 February to 31 March and the second from 20 April to 20 May; larvae showed similar, but slightly lagged, pulses. Based on generalized cross‐validation and information theory, a GAM model that allowed for different seasonal patterns in egg density within three unique areas outperformed a GAM that assumed a single fixed seasonal pattern across the entire eastern Bering Sea. This ‘area‐dependent’ GAM predicted the highest densities of eggs (i.e., potential spawning locations) in three major areas of the eastern Bering Sea: near Bogoslof Island (February–April), north of Unimak Island and the Alaska Peninsula (March–April), and around the Pribilof Islands (April–August). Unique temporal patterns of egg density were observed for each area, suggesting that pollock spawning may be more spatially and temporally complex than previously assumed. Moreover, this work provides a valuable baseline of pollock spawning to which future changes, such as those resulting from climate variability, may be compared.
Fisheries replenishment of early life taxa: potential export of fish eggs and larvae from a temperate marine protected area
Authors: CREC’HRIOU R. , ALEMANY F. , ROUSSEL E. , CHASSANITE A. , MARINARO J. Y. , MADER J. , ROCHEL E. , PLANES S.
Published: March 2010

An ichthyoplankton survey was conducted at the periphery of Cabrera National Park (Balearic Islands, Western Mediterranean Sea) in July 2004, using bongo nets, fixed nets and collection of oceanographic data. This work focused on analysing the distribution of eggs and larval stages of some fishery‐targeted taxa (Coris julis, Epinephelus spp., Sciaena umbra and Scorpaena sp.) whose adult abundances and/or biomass are higher in the reserve and therefore would be likely to show gradients of larval abundance attributable to the existence of the Marine Protected Area (MPA). Oceanographic data indicated there was water column stratification, horizontal distribution of surface water masses and hydrodynamic features linked with Mediterranean seasonality. During the summer sampling, eggs and larvae of targeted fish taxa were mainly located in the northeast of the MPA, near the coast. An effect of depth and current was demonstrated for Coris julis and Epinephelus spp. and there appears to be an offshore gradient for the other targeted taxa, especially for the egg stages. These data highlight the fact that the Cabrera archipelago is a potential important spawning area for targeted fishery species.
Growth and catabolism in isotopic incorporation: a new formulation and experimental data
Authors: Carleton Scott A. , Del Rio Carlos Martinez
Published: March 2010

1. We propose a new model that uses an organism’s change in mass to estimate isotope incorporation rates. Our model is a re‐parameterization of a widely used one‐compartment‐first‐order kinetic model that estimates the rate of isotopic incorporation as a function of time. If animals are growing exponentially and fractional growth rates are measured, the time model allows partitioning the contribution of growth and catabolic turnover to isotopic incorporation. The model can be extended to include more than one‐compartment.

2. Our model makes the same assumptions but uses mass change as an independent variable. It estimates the ratio of the contribution of catabolic turnover to growth.

3. To test the model, we fed juvenile Nile tilapia (Oreochromis niloticus) at three different rations and measured their change in mass and tissue δ13C isotopic composition for 128 days.

4. Fish grew exponentially and fractional growth rates differed significantly between rations. The contribution of catabolism (tissue replacement) to isotopic incorporation was 2·6 to 5 times higher than growth (tissue addition) in liver. In muscle tissue, the contribution of catabolism and growth were roughly equivalent for all rations.

5. When we used the parameters of the mass model to re‐parameterize the time model we found a relatively good fit (r2 = 0·8 ± 0·1, mean ± SD) to the isotopic incorporation data.

6. The mass model estimated a smaller, and more biologically realistic range of δ∞ values than did the time model which suggests that it might yield better results when isotopic incorporation experiments are not carried on long enough to yield estimates of the asymptotic isotopic value of an animal’s tissues after a diet shift.

7. Rather than being alternatives, the time and mass models are complementary in that they allow us to see the same phenomenon from different perspectives.
Mechanics of bite force production and its relationship to diet in bats
Authors: Santana Sharlene E. , Dumont Elizabeth R. , Davis Julian L.
Published: March 2010

1. In vertebrates, bite force is a measure of whole organism performance that is associated with both cranial morphology and dietary ecology. Mechanistic studies of bite force production have identified morphological features associated with bite force, and linked bite force with diet, but this approach has rarely been used in mammals.

2. Mammals are a good system with which to investigate the function of the feeding apparatus because of the relative simplicity of their skulls and their high dietary diversity. Phyllostomid bats are one of the most trophically and morphologically diverse groups of mammals, but we know little about the relative importance of biomechanical variables in producing bite force or how these variables vary with diet.

3. We combined in vivo measurements of bite force with assessments of muscular and bony morphology to build and validate a model describing the mechanics of bite force production in 25 species of bats. We used this model to investigate how bats with different diets vary in biomechanical parameters that contribute to bite force. In addition to traditional dietary categories, we used a functional definition of diet that reflects the mechanical demands (hardness) of the food items in the natural diet.

4. Our model provided good predictions of in vivo bite forces and highlighted behavioural variation that is inherent in the in vivo data. The temporalis generates the highest moment about the temporomandibular joint (TMJ) axis, but the moment generated by the masseter is the most important variable in explaining variation among species. The dietary classification based on the hardness of the diet was more effective than traditional dietary categories in describing biomechanical differences among groups. The temporalis generated the highest proportion of the moment about the TMJ axis in species with very hard and hard diets, the masseter was most important for species with soft diets, and the medial pterygoid was most important for species with liquid diets.

5. Our results highlight the utility of combining a modelling approach with in vivo data when conducting ecomorphological studies, and the importance of ecological classifications that reflect functional importance of performance traits.
Facilitation of Quercus ilex in Mediterranean shrubland is explained by both direct and indirect interactions mediated by herbs
Authors: Cuesta Bárbara , Villar‐Salvador Pedro , Puértolas Jaime , Rey Benayas José M. , Michalet Richard
Published: March 2010

1. Competitive and facilitative interactions shape plant communities. Whereas a number of studies have addressed competition and direct facilitation among plants in dry ecosystems, indirect facilitation has received little attention.

2. We investigated the relative importance of direct and indirect facilitation by the nurse plant Retama sphaerocarpa on late‐successional Quercus ilex seedlings mediated by herb suppression in a Mediterranean shrubland in 2006 and 2007. We also studied whether facilitation outcome depended on the size of the facilitated seedlings.

3. A field experiment was carried out to test the effect of (i) position of Q. ilex seedling with respect to shrub canopy (under shrubs or in gaps), (ii) herb competition (presence or absence), and (iii) seedling size. 2006 was an average rainfall year while 2007 had a much more humid spring and a dryer summer than 2006.

4. In both years, nurse shrubs reduced seedling mortality whereas herbs increased it. In the average rainfall year, seedling mortality under shrubs was unaffected by herbs whereas in gaps it was significantly higher in presence of herbs. This showed that the nurse shrub indirectly facilitated the seedlings by reducing the competitive capacity of herbs. Conversely, facilitation was predominately direct during the humid spring and dry summer year since herbs hindered seedling survival similarly under the nurse shrub and in gaps. The nurse shrub directly facilitated the seedlings by reducing seedling photoinhibition and water stress.

5. Improvement of environmental conditions by Retama benefited smaller seedlings but not larger seedlings since the nurse shrub reduced mortality of smaller seedlings relative to that in gaps, but this effect was not observed for larger seedlings. This indicates that individuals within a seedling population may not have the same response to facilitation.

6. Synthesis. Both indirect and direct facilitation are important mechanisms for Q. ilex regeneration in Retama shrubland and their importance seems to vary with climatic conditions. Indirect facilitation by release of herb competition under nurse shrubs is important in years of dry springs when competition between nurse shrubs and herbs is high, whereas direct facilitation mediated by microclimate amelioration increases with summer aridity.
MicA sRNA links the PhoP regulon to cell envelope stress
Authors: Coornaert Audrey , Lu Alisa , Mandin Pierre , Springer Mathias , Gottesman Susan , Guillier Maude
Published: March 2010

Numerous small RNAs regulators of gene expression exist in bacteria. A large class of them binds to the RNA chaperone Hfq and act by base pairing interactions with their target mRNA, thereby affecting their translation and/or stability. They often have multiple direct targets, some of which may be regulators themselves, and production of a single sRNA can therefore affect the expression of dozens of genes. We show in this study that the synthesis of the Escherichia coli pleiotropic PhoPQ two‐component system is repressed by MicA, a σE‐dependent sRNA regulator of porin biogenesis. MicA directly pairs with phoPQ mRNA in the translation initiation region of phoP and presumably inhibits translation by competing with ribosome binding. Consequently, MicA downregulates several members of the PhoPQ regulon. By linking PhoPQ to σE, our findings suggest that major cellular processes such as Mg2+ transport, virulence, LPS modification or resistance to antimicrobial peptides are modulated in response to envelope stress. In addition, we found that Hfq strongly affects the expression of phoP independently of MicA, raising the possibility that even more sRNAs, which remain to be identified, could regulate PhoPQ synthesis.
A standard set of host differentials and unified nomenclature for an international collection of Diplocarpon rosae races
Authors: Whitaker V. M. , Debener T. , Roberts A. V. , Hokanson S. C.
Published: March 2010

Black spot of rose is distributed throughout the world and is the most serious disease of roses (Rosa spp.) in the outdoor landscape. Resistance breeding has been frustrated by the occurrence of races of the causal pathogen Diplocarpon rosae. Races from Germany, North America and the UK have been characterized and maintained in a pathogenic state. However, these races were characterized using independent sets of host genotypes and are referenced using different nomenclatures. In the present study, a total of 15 D. rosae isolates from these locations, as well as Belgium and Italy, were inoculated to a common set of 15 rose cultivars in replicated, detached leaf trials. Baby LoveTM (cv. Scrivluv) was resistant to all isolates except for one originating from the UK. The rose cultivars Mrs Doreen Pike (Ausdor) and Hansa were resistant to all isolates except for one originating from Minnesota, USA. No rose genotype was universally susceptible. A total of 11 pathogenic races were differentiated based on their unique host ranges and were assigned an international race nomenclature. Nine cultivars are proposed as the first standard set of differential genotypes for characterization of D. rosae races.
Pharmacological and non‐drug treatment of child bipolar I disorder during prospective eight‐year follow‐up
Authors: Geller Barbara , Tillman Rebecca , Bolhofner Kristine , Zimerman Betsy
Published: March 2010

Geller B, Tillman R, Bolhofner K, Zimerman B. Pharmacological and non‐drug treatment of child bipolar I disorder during prospective eight‐year follow‐up. Bipolar Disord 2010: 12: 164–171. © 2010 The Authors. Journal compilation © 2010 John Wiley & Sons A/S.

Objectives:  The Phenomenology and Course of Pediatric Bipolar Disorders study, a National Institute of Mental Health‐funded study of child bipolar I disorder (BP‐I) begun in 1995, is a prospective follow‐up study that included collecting pharmacological and non‐drug treatment data.

Methods:  There were 115 first‐episode subjects who fit full DSM‐IV criteria for BP‐I, mixed or manic phase, with severity scores in the clinically impaired range, ascertained by consecutive new case ascertainment. Subjects were assessed with the Washington University in St. Louis Kiddie Schedule for Affective Disorders and Schizophrenia (WASH‐U‐KSADS), given separately to parents about their children and to children about themselves. All treatment was provided by the subjects’ own community practitioners, exactly as if they had not been in the research study. Thus, families were only seen for research assessments, and research staff were not at all involved in their treatment. Data on type, dose, and duration of pharmacological and non‐drug treatment were collected. During follow‐up, 93.9% (n = 108) were assessed at each of the nine assessment times.

Results:  During the eight years, only 62.6% received any antimanic medication (antipsychotic, anticonvulsant, lithium) at any time. Percents who received non‐antimanic medication included 77.4% medication for attention‐deficit hyperactivity disorder and 64.3% antidepressants. A total of 67.8% of subjects were taking two or more concurrent medication classes. Subjects ascertained from psychiatric versus pediatric sites received antimanics significantly more frequently (p = 0.006). Earlier recovery during eight‐year follow‐up was predicted by greater percent of weeks on lithium (p = 0.017).

Conclusions:  Given these findings, and the poor prognosis from prospective follow‐up of this sample reported elsewhere, there is a need for further research that informs the development of effective treatment strategies.
Enhanced working and verbal memory after lamotrigine treatment in pediatric bipolar disorder
Authors: Pavuluri Mani N , Passarotti Alessandra M , Mohammed Tahseen , Carbray Julie A , Sweeney John A
Published: March 2010

Pavuluri MN, Passarotti AM, Mohammed T, Carbray JA, Sweeney JA. Enhanced working and verbal memory after lamotrigine treatment in pediatric bipolar disorder. Bipolar Disord 2010: 12: 213–220. © 2010 The Authors. Journal compilation © 2010 John Wiley & Sons A/S.

Objective:  To examine the treatment impact of lamotrigine on the neurocognitive profile of patients with pediatric bipolar disorder (PBD).

Method:  Healthy controls (HC) (n = 24; mean age = 12.4 ± 3.3 years) and unmedicated PBD patients with manic, mixed, or hypomanic episodes (n = 34; mean age = 13 ± 3.1 years) were matched for IQ, age, sex, race, and socioeconomic status. A neurocognitive battery was administered at baseline and again after 14 weeks, during which PBD patients were treated with lamotrigine.

Results:  Clinical symptoms improved with treatment in the patient group with significant change from baseline to follow‐up on the Young Mania Rating Scale (p < 0.001) and the Children’s Depression Rating Scale–Revised (p < 0.001). Global neurocognitive function improved with lamotrigine in PBD patients over time relative to that in HC, although overall performance remained impaired. Working memory and verbal memory significantly improved with treatment in patients, and deficits in these domains were no longer significantly impaired relative to HC at follow‐up. Executive function significantly improved with treatment in the patient group but still lagged behind HC at follow‐up. Performance on attention tests did not improve with treatment.

Conclusions:  There appears to be significant improvement in cognitive abilities in PBD patients treated with lamotrigine that is most prominent in the areas of working memory and verbal memory and that occurs along with mood stabilization.
Clinical characteristics of comorbid obsessive‐compulsive disorder and bipolar disorder in children and adolescents
Authors: Joshi Gagan , Wozniak Janet , Petty Carter , Vivas Fe , Yorks Dayna , Biederman Joseph , Geller Daniel
Published: March 2010

Joshi G, Wozniak J, Petty C, Vivas F, Yorks D, Biederman J, Geller D. Clinical characteristics of comorbid obsessive‐compulsive disorder and bipolar disorder in children and adolescents. Bipolar Disord 2010: 12: 185–195. © 2010 The Authors. Journal compilation © 2010 John Wiley & Sons A/S.

Objective:  To explore bidirectional comorbidity between bipolar disorder (BPD) and obsessive‐compulsive disorder (OCD) in youth and to examine the symptom profile and clinical correlates of both disorders in the context of reciprocal comorbidity and ascertainment status.

Methods:  Two samples of consecutively referred youth (ages 6–17 years) ascertained contemporaneously for respective studies of BPD and OCD were compared using clinical and scalar assessment and structured diagnostic interviews.

Results:  A total of 21% (17/82) of the BPD subjects and 15% (19/125) of the OCD subjects met DSM‐III‐R diagnostic criteria for both disorders. In the presence of BPD, youth with OCD more frequently experienced hoarding/saving obsessions and compulsions along with a clinical profile of greater comorbidity, poorer global functioning, and higher rate of hospitalization that is characteristic of BPD. Multiple anxiety disorders (≥ 3), especially generalized anxiety disorder and social phobia, were present at a higher frequency when OCD and BPD were comorbid than otherwise. In subjects with comorbid OCD and BPD, the primary disorder of ascertainment was associated with an earlier onset and more severe impairment.

Conclusions:  An unexpectedly high rate of comorbidity between BPD and OCD was observed in youth irrespective of primary ascertainment diagnosis. In youth with comorbid OCD and BPD, the clinical characteristics of each disorder run true and are analogues to their clinical presentation in youth without reciprocal comorbidity, with the exception of increased risk for obsessions and compulsions of hoarding/saving and comorbidity with other anxiety disorders.
Metabolic effects of second‐generation antipsychotics in bipolar youth: comparison with other psychotic and nonpsychotic diagnoses
Authors: Moreno Carmen , Merchán‐Naranjo Jessica , Álvarez Mar , Baeza Inmaculada , Alda Jose A , Martínez‐Cantarero Carmen , Parellada Mara , Sánchez Bernardo , De La Serna Elena , Giráldez Marisa , Arango Celso
Published: March 2010

Moreno C, Merchán‐Naranjo J, Álvarez M, Baeza I, Alda JA, Martínez‐Cantarero C, Parellada M, Sánchez B, de la Serna E, Giráldez M, Arango C. Metabolic effects of second‐generation antipsychotics in bipolar youth: comparison with other psychotic and nonpsychotic diagnoses. Bipolar Disord 2010: 12: 172–184. © 2010 The Authors. Journal compilation © 2010 John Wiley & Sons A/S.

Objectives:  Despite known metabolic effects of second‐generation antipsychotics (SGAs) on children and adolescents, comparative effects in youth with different diagnoses remain underreported. We compared differences in metabolic changes three months after starting treatment with SGAs in youth with bipolar disorder and with other psychotic and nonpsychotic disorders.

Methods:  Weight and metabolic differences among diagnostic groups before and three months after starting treatment with SGAs were compared in a naturalistic cohort of children and adolescents (14.9 ± 3.0 years) diagnosed with bipolar disorder (n = 31), other psychotic disorders (n = 29), and other nonpsychotic disorders (n = 30), with no (35.6%) or very little (6.6 ± 9.0 days) previous exposure to antipsychotics. Composite measurements of significant weight gain [weight increase ≥ 5% at three months or increase ≥ 0.5 in body mass index (BMI) z‐score] and ‘risk for adverse health outcome’ (≥ 95th BMI percentile, or ≥ 85th BMI percentile plus presence of one other obesity‐related complication) were included. SGAs (risperidone, olanzapine, and quetiapine) were prescribed in comparable proportion among groups.

Results:  Baseline weight and metabolic indices were not significantly different among diagnoses. Three months after starting treatment with SGAs, more than 70% patients had significant weight gain, BMI z‐score increased in all diagnostic groups (p < 0.001 for all comparisons), total cholesterol increased in the bipolar (p = 0.02) and psychotic (p = 0.01) disorder groups, low‐density lipoprotein cholesterol increased in the bipolar group (p = 0.02), and free T4 decreased in the psychotic disorder group (p = 0.05). More patients with bipolar disorder presented overweight plus ≥ 1 obesity‐related complication at follow‐up.

Conclusions:  There are early weight gain and metabolic changes across diagnoses in youth treated with SGAs.
Antipsychotic and mood stabilizer efficacy and tolerability in pediatric and adult patients with bipolar I mania: a comparative analysis of acute, randomized, placebo‐controlled trials
Authors: Correll Christoph U , Sheridan Eva M , DelBello Melissa P
Published: March 2010

Correll CU, Sheridan EM, DelBello MP. Antipsychotic and mood stabilizer efficacy and tolerability in pediatric and adult patients with bipolar I mania: a comparative analysis of acute, randomized, placebo‐controlled trials. Bipolar Disord 2010: 12: 116–141. © 2010 The Authors. Journal compilation © 2010 John Wiley & Sons A/S.

Objective:  To compare antipsychotic and mood stabilizer (MS) efficacy and tolerability in youth and adults with bipolar mania.

Methods:  Medline/PubMed search for studies including: (i) youth (< 18 years) or adults (≥ 18 years); (ii) bipolar I disorder; (iii) double‐blind, randomized, placebo‐controlled trial (DB‐RPCT); (iv) ≤ 12 weeks of treatment; and (v) calculable effect sizes (ES) and/or numbers needed to treat/harm (NNT/NNH) ± 95% confidence intervals (CI). Non‐overlapping 95% CIs determined significant group differences.

Results:  We identified nine DB‐RPCTs in youth (n = 1,609), 5 evaluating second‐generation antipsychotics (SGAs) (n = 1,140) and 4 evaluating MSs (n = 469). We also identified 23 DB‐RPCTs in adults (n = 6,501), 14 including SGAs (n = 3,297), 5 using haloperidol as an active comparator (n = 580), and 11 including MSs (n = 2,581). Young Mania Rating Scale scores improved significantly more with SGAs than MSs in youth (ES = 0.65, CI: 0.53–0.78 versus 0.24, CI: 0.06–0.41) and adults (ES = 0.48, CI: 0.41–0.55 versus 0.24, CI: 0.17–0.31). After excluding topiramate studies, SGAs had larger ES than MSs only in youth (ES = 0.65, CI: 0.53–0.78 versus 0.20, CI: 0.02–0.39), but not adults (ES = 0.48, CI: 0.41–0.55 versus 0.46, CI: 0.37–0.55). However, in adults SGAs had significantly larger ES regarding Clinical Global Impressions scores than MSs, even without topiramate (ES = 0.75, CI: 0.68–0.82 versus 0.24, CI: 0.07–0.41). Rates of response, remission, and discontinuation due to any reason compared to placebo were similar between medication and age groups, except for more favorable NNTs for remission with SGAs than MSs in adults after excluding topiramate. SGAs caused more weight gain than MSs in youth (ES = 0.53, CI: 0.41–0.66 versus 0.10, CI: −0.12–0.33), but not in adults (ES = 0.13, CI: 0.05–0.22 versus 0.00, CI: −0.08–0.08). However, results were heterogeneous and not significant in either age group after excluding topiramate. Nevertheless, SGA‐related weight gain was significantly greater in youth than adults. In youth, SGA‐related somnolence was greater than with MSs (NNH = 4.7, CI: 3.9–6.0 versus 9.5, CI: 6.3–23.5), and more likely than in adults (NNH = 7.1, CI: 6.1–8.8). Conversely, youth experienced less akathisia with SGAs than adults (NNH = 20.4, CI: 14.1–36.5 versus 10.2, CI: 8.1–13.7), likely due to lower doses/slower titration.

Conclusions:  In treating mania, potentially greater short‐term efficacy compared to placebo with SGAs versus MS needs to be balanced against increased adverse events, especially in youth.
Habitat use affects morphological diversification in dragon lizards
Authors: COLLAR D. C. , SCHULTE J. A. , O’MEARA B. C. , LOSOS J. B.
Published: March 2010

Habitat use may lead to variation in diversity among evolutionary lineages because habitats differ in the variety of ways they allow for species to make a living. Here, we show that structural habitats contribute to differential diversification of limb and body form in dragon lizards (Agamidae). Based on phylogenetic analysis and ancestral state reconstructions for 90 species, we find that multiple lineages have independently adopted each of four habitat use types: rock‐dwelling, terrestriality, semi‐arboreality and arboreality. Given these reconstructions, we fit models of evolution to species’ morphological trait values and find that rock‐dwelling and arboreality limit diversification relative to terrestriality and semi‐arboreality. Models preferred by Akaike information criterion infer slower rates of size and shape evolution in lineages inferred to occupy rocks and trees, and model‐averaged rate estimates are slowest for these habitat types. These results suggest that ground‐dwelling facilitates ecomorphological differentiation and that use of trees or rocks impedes diversification.
Large‐brained mammals live longer
Authors: GONZÁLEZ‐LAGOS C. , SOL D. , READER S. M.
Published: March 2010

Many mammals have brains substantially larger than expected for their body size, but the reasons for this remain ambiguous. Enlarged brains are metabolically expensive and require elongated developmental periods, and so natural selection should have favoured their evolution only if they provide counterbalancing advantages. One possible advantage is facilitating the construction of behavioural responses to unusual, novel or complex socio‐ecological challenges. This buffer effect should increase survival rates and favour a longer reproductive life, thereby compensating for the costs of delayed reproduction. Here, using a global database of 493 species, we provide evidence showing that mammals with enlarged brains (relative to their body size) live longer and have a longer reproductive lifespan. Our analysis supports and extends previous findings, accounting for the possible confounding effects of other life history traits, ecological and dietary factors, and phylogenetic autocorrelation. Thus, these findings provide support for the hypothesis that mammals counterbalance the costs of affording large brains with a longer reproductive life.
Estimating the ratio of effective to actual size of an age‐structured population from individual demographic data
Authors: Engen S. , Lande R. , Sæther B.‐E. , Gienapp P.
Published: March 2010

The effective population size is a central concept for understanding evolutionary processes in a finite population. We employ Fisher's reproductive value to estimate the ratio of effective to actual population size for an age‐structured population with two sexes using random samples of individual vital rates. The population may be subject to environmental stochasticity affecting the vital rates. When the mean sex ratio at birth is known, improved efficiency is obtained by utilizing the records of total number of offspring rather than considering separately female and male offspring. We also show how to incorporate uncertain paternity.
Egg phenotype differentiation in sympatric cuckooCuculus canorusgentes
Authors: ANTONOV A. , STOKKE B. G. , VIKAN J. R. , FOSSøY F. , RANKE P. S. , RØSKAFT E. , MOKSNES A. , MØLLER A. P. , SHYKOFF J. A.
Published: March 2010

The brood parasitic common cuckooCuculus canorusconsists of gentes, which typically parasitize only a single host species whose eggs they often mimic. Where multiple cuckoo gentes co‐exist in sympatry, we may expect variable but generally poorer mimicry because of host switches or inter‐gens gene flow via males if these also contribute to egg phenotypes. Here, we investigated egg trait differentiation and mimicry in three cuckoo gentes parasitizing great reed warblersAcrocephalus arundinaceus, marsh warblersAcrocephalus palustrisand corn buntingsMiliaria calandrabreeding in close sympatry in partially overlapping habitat types. The three cuckoo gentes showed a remarkable degree of mimicry to their three host species in some but not all egg features, including egg size, a hitherto largely ignored feature of egg mimicry. Egg phenotype matching for both background and spot colours as well as for egg size has been maintained in close sympatry despite the possibility for gene flow.
A general model of the public goods dilemma
Authors: Frank S. A.
Published: March 2010

An individually costly act that benefits all group members is a public good. Natural selection favours individual contribution to public goods only when some benefit to the individual offsets the cost of contribution. Problems of sex ratio, parasite virulence, microbial metabolism, punishment of noncooperators, and nearly all aspects of sociality have been analysed as public goods shaped by kin and group selection. Here, I develop two general aspects of the public goods problem that have received relatively little attention. First, variation in individual resources favours selfish individuals to vary their allocation to public goods. Those individuals better endowed contribute their excess resources to public benefit, whereas those individuals with fewer resources contribute less to the public good. Thus, purely selfish behaviour causes individuals to stratify into upper classes that contribute greatly to public benefit and social cohesion and to lower classes that contribute little to the public good. Second, if group success absolutely requires production of the public good, then the pressure favouring production is relatively high. By contrast, if group success depends weakly on the public good, then the pressure favouring production is relatively weak. Stated in this way, it is obvious that the role of baseline success is important. However, discussions of public goods problems sometimes fail to emphasize this point sufficiently. The models here suggest simple tests for the roles of resource variation and baseline success. Given the widespread importance of public goods, better models and tests would greatly deepen our understanding of many processes in biology and sociality.
Fruit compounds affect male sexual success in the South American fruit fly, Anastrepha fraterculus (Diptera: Tephritidae)
Authors: Vera M. T. , Ruiz M. J. , Oviedo A. , Abraham S. , Mendoza M. , Segura D. F. , Kouloussis N. A. , Willink E.
Published: March 2010

Although exposure to plants has been shown to influence sexual behaviour in a number of phytophagous insect species, a relatively small number of fruit flies have been investigated in that respect. Here, we evaluated the effect of exposure to the pulp of guava and mango and to essential oils emanating from glands in the flavedo area of lemons on the mating success of Anastrepha fraterculus (Wiedemann) (Diptera: Tephritidae) males. We also evaluated different durations of exposure and the need for physical contact with the fruit. Results showed that exposure to guava increased the mating success of both wild and laboratory males relative to non‐exposed males. In addition, exposed wild flies copulated earlier than non‐exposed males. Physical contact with the fruit or ingestion of compounds was not a prerequisite for this phenomenon to occur, since just the exposure to volatiles resulted in a significant enhancement in mating success. Exposure to mango did not affect male sexual performance. In contrast, exposure to lemon for 1 day decreased mating success of males relative to unexposed males, whereas exposure for longer periods seemed to eliminate this effect resulting in comparable mating success rates between treated and untreated males. These results provide a better understanding of the sexual behaviour of this species and may also find application for its control.