bluuebunny/crossref_metadata_2025 huggingface dataset:
Using novel biomarkers to triage young adult women with minor cervical lesions: a cost‐effectiveness analysis
Authors: Pedersen K , Sørbye SW , Kristiansen IS , Burger EA
Published: June 2016

Objective

To evaluate the short‐term consequences and cost‐effectiveness associated with the use of novel biomarkers to triage young adult women with minor cervical cytological lesions.

Design

Model‐based economic evaluation using primary epidemiological data from Norway, supplemented with data from European and American clinical trials.

Setting

Organised cervical cancer screening in Norway.

Population

Women aged 25–33 years with minor cervical cytological lesions detected at their primary screening test.

Methods

We expanded an existing simulation model to compare 12 triage strategies involving alternative biomarkers (i.e. reflex human papillomavirus (HPV) DNA/mRNA testing, genotyping, and dual staining) with the current Norwegian triage guidelines.

Main outcome measures

The number of high‐grade precancers detected and resource use (e.g. monetary costs and colposcopy referrals) for a single screening round (3 years) for each triage strategy. Cost‐efficiency, defined as the additional cost per additional precancer detected of each strategy compared with the next most costly strategy.

Results

Five strategies were identified as cost‐efficient, and are projected to increase the precancer detection rate between 18 and 57%, compared with current guidelines; however, the strategies did not uniformly require additional resources. Strategies involving HPV mRNA testing required fewer resources, whereas HPV DNA‐based strategies detected >50% more precancers, but were more costly and required twice as many colposcopy referrals compared with the current guidelines.

Conclusion

Strategies involving biomarkers to triage younger women with minor cervical cytological lesions have the potential to detect additional precancers, yet the optimal strategy depends on the resources available as well as decision‐makers' and women's acceptance of additional screening procedures.

Tweetable abstract

Women with minor cervical lesions may be triaged more accurately and effectively using novel biomarkers.
Fluctuation in seed abundance has contrasting effects on the fate of seeds from two rapidly germinating tree species in an Asian tropical forest
Authors: CAO Lin , GUO Cong , CHEN Jin
Published: June 2016

The seed predator satiation hypothesis states that high seed abundance can satiate seed predators or seed dispersers, thus promoting seed survival. However, for rapidly germinating seeds in tropical forests, high seed abundance may limit dispersal as the seeds usually remain under parent trees for long periods, which may lead to high mortality due to rodent predation or fungal infestations. By tracking 2 species of rapidly germinating seeds (Pittosporopsis kerrii, family Icacinaceae; Camellia kissi, family Theaceae), which depend on dispersal by scatter‐hoarding rodents, we investigated the effects of seed abundance at the community level on predation and seed dispersal in the tropical forest of Xishuangbanna Prefecture, Southwest China. We found that high seed abundance at the community level was associated with delayed and reduced seed removal, decreased dispersal distance and increased pre‐dispersal seed survival for both plant species. High seed abundance was also associated with reduced seed caching of C. kissi, but it showed little effect on seed caching of P. kerrii. However, post‐dispersal seed survival for the 2 plant species followed the reverse pattern. High seed abundance in the community was associated with higher post‐dispersal survival of P. kerrii seeds, but with lower post‐dispersal survival of C. kissi seeds. Our results suggest that different plant species derive benefit from fluctuations in seed production in different ways.
The scaling of bite force and constriction pressure in kingsnakes (Lampropeltis getula): Proximate determinants and correlated performance
Authors: PENNING David A.
Published: June 2016

Across the diversity of vertebrates, bite force has been studied and suggested to have important ecological and evolutionary consequences. However, there is a notable lineage of vertebrates that use this performance trait yet are missing from the bite‐force literature: the snakes. Snakes often rely on biting during prey subjugation and handling. Many snakes bite and hold prey while a constriction coil is formed or while venom is being delivered, or both. Others use biting exclusively without employing any additional prey‐handling behaviors. In addition to biting, constriction is an important predation mechanism. Here, I quantify bite force and constriction pressure in kingsnakes (Lampropeltis getula). Furthermore, I explore the proximate determinants of bite force as well as the relationship between biting and constriction performance. Bite force increased linearly with all head and body measures. Of these, head height was the best predictor of bite force. Bite force in kingsnakes was within the range of values reported for lizards, but their relative performance was lower for their head size compared to lizards. Peak constriction pressure also increased with all body measures. Biting and constricting use 2 different parts of the musculoskeletal system and are positively and significantly correlated with one another. Future work targeting a greater diversity of snakes that rely more heavily on biting may reveal a greater range of bite performance in this diverse and successful vertebrate group.
Bacterial microbiomes from vertically transmitted fungal inocula of the leaf‐cutting ant Atta texana
Authors: Meirelles Lucas A. , McFrederick Quinn S. , Rodrigues Andre , Mantovani Joana D. , de Melo Rodovalho Cynara , Ferreira Henrique , Bacci Maurício , Mueller Ulrich G.
Published: June 2016

Microbiome surveys provide clues for the functional roles of symbiotic microbial communities and their hosts. In this study, we elucidated bacterial microbiomes associated with the vertically transmitted fungal inocula (pellets) used by foundress queens of the leaf‐cutting ant Atta texana as starter‐cultures for new gardens. As reference microbiomes, we also surveyed bacterial microbiomes of foundress queens, gardens and brood of incipient nests. Pseudomonas, Acinetobacter, Propionibacterium and Corynebacterium were consistently present in high abundance in microbiomes. Some pellet and ant samples contained abundant bacteria from an Entomoplasmatales‐clade, and a separate PCR‐based survey of Entomoplasmatales bacteria in eight attine ant‐genera from Brazil placed these bacteria in a monophyletic clade within the bacterial genus Mesoplasma. The attine ant‐Mesoplasma association parallels a similar association between a closely related, monophyletic Entomoplasmatales‐clade and army ants. Of thirteen A. texana nests surveyed, three nests with exceptionally high Mesoplasma abundance died, whereas the other nests survived. It is unclear whether Mesoplasma was the primary cause of mortality, or Mesoplasma became abundant in moribund nests for non‐pathogenic reasons. However, the consistent and geographically widespread presence of Mesoplasma suggests an important functional role in the association with attine ants.
Bacterial communities in Arctic first‐year drift ice during the winter/spring transition
Authors: Eronen‐Rasimus Eeva , Piiparinen Jonna , Karkman Antti , Lyra Christina , Gerland Sebastian , Kaartokallio Hermanni
Published: June 2016

Horizontal and vertical variability of first‐year drift‐ice bacterial communities was investigated along a North–South transect in the Fram Strait during the winter/spring transition. Two different developmental stages were captured along the transect based on the prevailing environmental conditions and the differences in bacterial community composition. The differences in the bacterial communities were likely driven by the changes in sea‐ice algal biomass (2.6—5.6 fold differences in chl‐a concentrations). Copiotrophic genera common in late spring/summer sea ice, such as Polaribacter, Octadecabacter and Glaciecola, dominated the bacterial communities, supporting the conclusion that the increase in the sea‐ice algal biomass was possibly reflected in the sea‐ice bacterial communities. Of the dominating bacterial genera, Polaribacter seemed to benefit the most from the increase in algal biomass, since they covered approximately 39% of the total community at the southernmost stations with higher (>6 μg l−1) chl‐a concentrations and only 9% at the northernmost station with lower chl‐a concentrations (<6 μg l−1). The sea‐ice bacterial communities also varied between the ice horizons at all three stations and thus we recommend that for future studies multiple ice horizons be sampled to cover the variability in sea‐ice bacterial communities in spring.
Coexistence of two d‐lactate‐utilizing systems in Pseudomonas putida KT2440
Authors: Zhang Yingxin , Jiang Tianyi , Sheng Binbin , Long Yangdanyu , Gao Chao , Ma Cuiqing , Xu Ping
Published: June 2016

It is advantageous for rhizosphere‐dwelling microorganisms to utilize organic acids such as lactate. Pseudomonas putida KT2440 is one of the most widely studied rhizosphere‐dwelling model organisms. The P. putida KT2440 genome contains an NAD‐dependent d‐lactate dehydrogenase encoding gene, but mutation of this gene does not play a role in d‐lactate utilization. Instead, it was found that d‐lactate utilization in P. putida KT2440 proceeds via a multidomain NAD‐independent d‐lactate dehydrogenase with a C‐terminal domain containing several Fe‐S cluster‐binding motifs (Fe‐S d‐iLDH) and glycolate oxidase, which is widely distributed in various microorganisms. Both Fe‐S d‐iLDH and glycolate oxidase were identified to be membrane‐bound proteins. Neither Fe‐S d‐iLDH nor glycolate oxidase is constitutively expressed but both of them can be induced by either enantiomer of lactate in P. putida KT2440. This study shows a case in which an environmental microbe contains two types of enzymes specific for d‐lactate utilization.
Restructuring of the sponge microbiome favors tolerance to ocean acidification
Authors: Ribes M. , Calvo E. , Movilla J. , Logares R. , Coma R. , Pelejero C.
Published: June 2016

Ocean acidification is increasing and affects many marine organisms. However, certain sponge species can withstand low‐pH conditions. This may be related to their complex association with microbes. We hypothesized that species with greater microbial diversity may develop functional redundancy that could enable the holobiont to survive even if particular microbes are lost at low‐pH conditions. We evaluated the effects of acidification on the growth and associated microbes of three ubiquitous Mediterranean sponges by exposing them to the present pH level and that predicted for the year 2100. We found marked differences among the species in the acquisition of new microbes, being high in Dysidea avara, moderate in Agelas oroides and null in Chondrosia reniformis; however, we did not observe variation in the overall microbiome abundance, richness or diversity. The relative abilities to alter the microbiomes contributes to survivorship in an OA scenario as demonstrated by lowered pH severely affecting the growth of C. reniformis, halving that of A. oroides, and unaffecting D. avara. Our results indicate that functional stability of the sponge holobiont to withstand future OA is species‐specific and is linked to the species’ ability to use horizontal transmission to modify the associated microbiome to adapt to environmental change.
The Value of Concept: Lessons from the Evolution of Antibiotic Resistance
Authors: Antonovics Janis
Published: June 2016

The evolution of resistance to antibiotics in disease causing pathogens is a major world‐wide threat to human health. This paper explores why regulatory, funding and institutional structures have inadequately addressed this issue, focusing on data from the US, but emphasizing that these issues are of global scope and applicability. There is an increasing call for serious acceptance of evolutionary biology by the medical community, but the failure to apply evolutionary ideas to the problem of antibiotic resistance continues. These ideas are deceptively simple in their basic formulation, but require sophisticated expertise when it comes to applying them in practice and to human health. The divergent histories of evolutionary biology and medical research have self‐referential constituencies in each field. The field of evolutionary biology does not see the applied issues associated with antibiotic resistance as part of its remit. At the biomedical research level, funding for research on evolution of antibiotic resistance is paltry compared to its importance as a health threat, regulatory requirements do not address evolutionary issues, institutional structures dealing with the issue are undeveloped, and there is even avoidance of the word ‘evolution’ in the context of antibiotic resistance. Current approaches to antibiotic resistance invoke evolutionary principles at a such a naive level that what is put forward are ineffective seat‐of‐the‐pants rules that have no strong theoretical basis and are almost always in desperate need of justification through evidence‐based research. Clear solutions exist but their implementation remains problematic.
The Limits of Cost/Benefit Analysis When Disasters Loom
Authors: Rose‐Ackerman Susan
Published: June 2016

Advances in estimating the costs and benefits of climate change policies are a welcome development, but a full‐scale cost/benefit analysis that seeks to reduce complex value trade‐offs to a single metric of net benefit maximization hides many important public policy issues, especially for disasters and catastrophes that are large, discontinuous, irreversible and uncertain. States should obtain public input on such policies. These policies involve value trade‐offs that can be informed by technocratic estimates of costs, benefits and risk. However, such analyses cannot, in principle, be reduced to a single recommendation that ‘maximizes net benefits’. Politicians must make value trade‐offs informed both by technocrats and by public input.
The Tragedy of the Uncommons: On the Politics of Apocalypse
Authors: Wiener Jonathan B.
Published: June 2016

The ‘tragedy of the commons’ is a classic type of problem, involving multiple actors who face individual incentives to deplete shared resources and thereby impose harms on others. Such tragedies can be overcome if societies learn through experience to mobilize collective action. This article formulates a distinct type of problem: ‘the tragedy of the uncommons’, involving the misperception and mismanagement of rare catastrophic risks. Although the problem of rare and global catastrophic risk has been much discussed, its sources and solutions need to be better understood. Descriptively, this article identifies psychological heuristics and political forces that underlie neglect of rare catastrophic ‘uncommons’ risks, notably the unavailability heuristic, mass numbing, and underdeterrence. Normatively, the article argues that, for rare catastrophic risks, it is the inability to learn from experience, rather than uncertainty, that offers the best case for anticipatory precaution. The article suggests a twist on conventional debates: in contrast to salient experienced risks spurring greater public concern than expert concern, rare uncommons risks exhibit greater expert concern than public concern. Further, optimal precaution against uncommons risks requires careful analysis to avoid misplaced priorities and potentially catastrophic risk–risk trade‐offs. The article offers new perspectives on expert vs public perceptions of risk; impact assessment and policy analysis; and precaution, policy learning and foresight.
Beyond Resilience: How to Better Prepare for the Profound Disruption of the Anthropocene
Authors: Kareiva Peter , Fuller Emma
Published: June 2016

Human activity is dramatically shaping all of Earth's natural systems, producing unprecedented challenges for people and nature. Climate disruption, altered hydrology, and ecosystem degradation reflect both threats to human wellbeing and changes in the ‘rules of the game’ that make management difficult. While ecologists, conservationists and environmental scientists clamor for radical action to reverse these threats, their own management actions in response to climate are too often business as usual. I hypothesize that restrictive and often unspoken mental models of ecological and environmental science are robbing these managers and their institutions of the flexibility required to respond to the Anthropocene's uncertain changes. The three most profound mental traps are: (1) an undue emphasis on historical reference points; (2) an ecological concept of resilience that fails to reckon with the Anthropocene's dynamism; and (3) a precautionary bias against new technologies and dramatic interventions. Caught in these mental traps, environmentalists too often reject entrepreneurial experimental approaches that could make them more relevant to policymakers, corporations and other institutions that seek to respond more proactively to impending disruption.
Medication Palatability Affects Physician Prescribing Preferences for Common Pediatric Conditions
Authors: Bradshaw Hans , Mitchell Michael J. , Edwards Christopher J. , Stolz Uwe , Naser Oday , Peck Amanda , Patanwala Asad E.
Published: June 2016

Objectives

The objective of this study was to determine if physicians would alter their prescribing preferences after sampling liquid formulations of medications for common pediatric diagnoses.

Methods

This was a prospective interventional before/after study conducted at an academic medical center in the United States. The participants of interest included emergency, family medicine, and pediatric physicians. Participants initially completed a brief survey for their primary oral liquid medication of choice for the treatment of selected disease states. These included otitis media, sinusitis, cellulitis, asthma, colitis, and pneumonia. Participants were asked to choose one of the medication options for each disease and then were given all medications to sample for a taste test. The prescribing preference survey was then repeated. The primary outcome was change in prescribing. McNemar's test was used to evaluate change in proportion of medications chosen before and after taste testing.

Results

There were 101 physicians who participated in the study. There were three conditions for which participants changed their prescribing preferences significantly. These were otitis media (change from amoxicillin to cefdinir, difference = 13.2%, 95% confidence interval [CI] = 5.5% to 21.0%), asthma exacerbation (change from dexamethasone or prednisone to prednisolone, 28%, 95% CI = 15.9% to 40.1%), and pneumonia (change from azithromycin to amoxicillin, 16.0%, 95% CI = 6.4% to 25.6%). There was no significant change with respect to the other scenarios.

Conclusions

Physicians showed preferences for certain pediatric medications based on taste and showed significant changes in prescribing preferences for some common pediatric diagnoses after tasting different medications for these conditions.
Alotanypus wilhelmensis sp. nov., a new Tanypodinae (Diptera: Chironomidae) from high mountain lakes in Papua New Guinea
Authors: da Silva Fabio Laurindo
Published: June 2016

A new species of Alotanypus Roback from high mountain lakes in Papua New Guinea is described and illustrated. Alotanypus wilhelmensis sp. nov. is described from male, female and pupa. The generic diagnoses for the male and immature stages are emended based on the new species and published descriptions of Gressittius and Guassutanypus, both recently suggested as junior synonyms of Alotanypus. Keys to known males, pupae and larvae of Alotanypus are provided.
Apoptotic Process Induced by Oxaliplatin in Rat Hippocampus Causes Memory Impairment
Authors: Bianchi Enrica , Di Cesare Mannelli Lorenzo , Micheli Laura , Farzad Mersedez , Aglianò Margherita , Ghelardini Carla
Published: June 2016

Aspects of memory involved in cognitive mechanisms were investigated in rat after oxaliplatin (OX) chemotherapy using animal behavioural assessment of passive avoidance and social learning paradigms, which are both hippocampus‐sensitive. Rodents, previously subjected to 2‐week OX treatment, showed passive avoidance and social learning impairment and apoptotic processes in the hippocampus. Apoptosis rate significantly increased in cultured hippocampal cells exposed to OX at increasing doses, and this effect was dose‐dependent. Ex vivo experiments showed that cell damage and apoptosis were blocked in the hippocampus from OX rats cotreated with copper sulphate (CS) which precludes OX transport inside the cell. In vivo, passive avoidance and social learning impairment could not be observed in OX rats co‐administered with CS. Thus, a site of action of OX treatment on memory impairment appears to be located at the hippocampus. These findings strongly support that cellular damage induced by OX in rodent hippocampus underlies the weakening of some memory functions.
The influence of baseline characteristics and disease stage on health‐related quality of life in multiple myeloma: findings from six randomized controlled trials
Authors: Robinson Don , Esseltine Dixie‐Lee , Regnault Antoine , Meunier Juliette , Liu Kevin , van de Velde Helgi
Published: June 2016

This descriptive, cross‐sectional analysis evaluated the impact of baseline characteristics on health‐related quality of life (HR‐QoL) at different stages of multiple myeloma (MM). The bortezomib clinical‐trial programme evaluated HR‐QoL early and consistently, producing a large multi‐study dataset. Baseline data, captured using the European Organization for Research and Treatment of Cancer (EORTC) quality‐of‐life questionnaire (QLQ‐C30), were pooled from six bortezomib randomized trials conducted in different disease‐stage categories: ‘New’ (previously untreated; n = 753), ‘Early’ (1–3 prior therapies; n = 1569) and ‘Late’ (≥4 prior therapies; n = 239) disease. Mean EORTC global health scores were similar across the three stages. Unexpectedly, emotional, physical and role functioning were higher in the later stages, indicating better perceived health. Symptom scores, including pain, were largely similar or lower in the later versus earlier stages, signifying a lower symptom burden/better symptom control with more advanced disease. Notable variation in HR‐QoL was observed by age and clinical parameters within and across stages. Multivariate modelling indicated that opioid use and performance status were key factors driving overall HR‐QoL across stages. Using an age‐restricted analysis, transplant eligibility had little impact on HR‐QoL in New disease patients. Thus, changes in HR‐QoL over the treatment course of MM are complex and impacted by baseline factors. A prospective observational international inception cohort study that captures key clinical, HR‐QoL and demographic characteristics, along with safety and supportive care information, is needed.
Unmanipulated haploidentical haematopoietic stem cell transplantation for children with severe aplastic anaemia
Authors: Zhu Hua , Luo Rong Mu , Luan Zuo , Lee Vincent , Zhu Yi Ping , Luo Cheng Juan , Tang Xiang Feng , Si Ying Jian , Chen Jing
Published: June 2016

Haploidentical haematopoietic stem cell transplantation (haplo‐HSCT) used to be a third‐line treatment option for childhood severe aplastic anaemia (SAA). We conducted this retrospective study of 36 children (38 transplants) who received haplo‐HSCT from human leucocyte antigen (HLA)‐mismatched related donors between July 2002 and November 2013 at five HSCT centres in China, including 17 cases that were 5/6 HLA matched (Group 1) and 21 that were 4/6 or 3/6 HLA matched (Group 2). Although patients in Group 2 had a higher incidence of grade II‐IV acute graft‐versus‐host disease (57·9% vs. 5·9%, P = 0·001), they had similar rates of graft failure (5·3% vs. 5·9%, P = 0·742) and overall survival (80·8% vs. 93·8%, P = 0·234) as Group 1. Unmanipulated haplo‐HSCT is an effective treatment for SAA children with satisfactory outcome of this cohort, especially in the 5/6 HLA‐matched group. For patients in critical situations, such as unresponsive to immunosuppressive therapy, refractory infection and failing first HSCT, to bring forward the timing of haplo‐HSCT is a feasible salvage strategy with better and faster donor accessibility.
Advances in the pathogenesis of primary and secondary haemophagocytic lymphohistiocytosis: differences and similarities
Authors: Brisse Ellen , Wouters Carine H. , Matthys Patrick
Published: June 2016

Haemophagocytic lymphohistiocytosis (HLH) comprises a heterogeneous spectrum of hyperinflammatory conditions that are inherited (primary HLH) or acquired in a context of infections, malignancies or autoimmune/autoinflammatory disorders (secondary HLH). Genetic defects in the cytotoxic machinery of natural killer and CD8+ T cells underlie primary HLH, with residual cytotoxicity determining disease severity. Improved sequencing techniques have expanded the range of causal mutations and have redefined many cases of secondary HLH as primary HLH and vice versa, blurring the distinction between both subtypes. These insights allow HLH to be conceptualized as a threshold disease, in which interplay between various genetic and environmental factors causes progressive inflammation into a critical point, beyond which uncontrolled activation of immune cells and excessive cytokine production give rise to the cardinal symptoms of HLH. Various pathogenic pathways may thus converge to a common end stage of fulminant HLH.
The Historical Roots of Autonomy in Nicaragua's Caribbean Coast: From British Colonialism to Indigenous Autonomy
Authors: BARACCO LUCIANO
Published: June 2016

This article reviews historical forms of localised government on Nicaragua's Caribbean coast and contrasts them with the contemporary struggle to attain a communal form of autonomy undertaken by the region's indigenous population. It suggests that the contemporary autonomy process shares few features with the historical precedents of localised government which are commonly invoked to legitimise it. Instead, its roots can be located in the emergence of a Moskitian nationalism amongst the Miskitu which occurred to counter the assimilating impulse of an increasingly developmentally determined national state during the 1960s under the Somoza dictatorship, and then more thoroughly during the Sandinista revolution.
The Challenge of ‘Territory’: Weaving the Social Fabric of Indigenous Communities in Nicaragua's Northern Caribbean Autonomous Region
Authors: LARSON ANNE M. , SOTO FERNANDA , MAIRENA DENNIS , MORENO EDDA , MAIRENA EILEEN , MENDOZA‐LEWIS JADDER
Published: June 2016

In Nicaragua, indigenous and afro‐descendant peoples' demands for territorial rights have become inseparable from demands for the exercise of autonomy in the Caribbean Coast. Alone, the new titles obtained by these communities, like the autonomy regime, will not guarantee legal security over collective lands, control over natural resources or the exercise of free determination. Through the analysis of three indigenous territories in Nicaragua's Northern Caribbean Coast Autonomous Region (RACCN), the article argues that the state is still setting the terms of debate. It suggests that the defence of rights should be anchored not only on the ownership of territory but also on the social fabric of indigenous communities and territories.
Territorial ‘Fix’? Tenure Insecurity in Titled Indigenous Territories
Authors: FINLEY‐BROOK MARY
Published: June 2016

Indigenous territorial governments in Nicaragua's North Caribbean Coast Autonomous Region experience ongoing land and resource contests, in many cases building from longstanding disputes or problems, even after titling. I argue that it is naïve to expect that granting titles – a supposed territorial fix – will resolve conflicts created across decades as a result of ineffective policies and economic pressures. As shown with three demarcated Miskitu territories, tenure insecurity arises from challenges with the state, private firms, non‐indigenous colonists, and even from the activities of territorial leaders. These cases suggest the need to move beyond perceptions of Miskitu territories as simple bounded remnants of the past and acknowledge they are complex, porous, trans‐local, and transgressed by processes such as migration, urbanisation, and neoliberal economic integration. Indeed, new territorial governments are encouraged by foreign donors and state laws to mirror government agencies and prioritise market linkages.
The contribution of undiagnosed adrenal insufficiency to euvolaemic hyponatraemia: results of a large prospective single‐centre study
Authors: Cuesta Martín , Garrahy Aoife , Slattery David , Gupta Saket , Hannon Anne Marie , Forde Hannah , McGurren Karen , Sherlock Mark , Tormey William , Thompson Christopher J.
Published: June 2016

Objective

The syndrome of inappropriate antidiuresis (SIAD) is the commonest cause of hyponatraemia. Data on SIAD are mainly derived from retrospective studies, often with poor ascertainment of the minimum criteria for the correct diagnosis. Reliable data on the incidence of adrenal failure in SIAD are therefore unavailable. The aim of the study was to describe the aetiology of SIAD and in particular to define the prevalence of undiagnosed adrenal insufficiency.

Design

Prospective, single centre, noninterventional, observational study of patients admitted to Beaumont Hospital with euvolaemic hyponatraemia (plasma sodium ≤ 130 mmol/l) between January 1st and October 1st 2015.

Patients

A total of 1323 admissions with hyponatraemia were prospectively evaluated; 576 had euvolaemic hyponatraemia, with 573 (43·4%) initially classified as SIAD.

Main outcome measures

(i) Aetiology of SIAD, defined by diagnostic criteria; (ii) Incidence of adrenal insufficiency.

Results

Central nervous system diseases were the commonest cause of SIAD (n = 148, 26%) followed by pulmonary diseases (n = 111, 19%), malignancy (n = 105, 18%) and drugs (n = 47, 8%). A total of 22 patients (3·8%), initially diagnosed as SIAD, were reclassified as secondary adrenal insufficiency on the basis of cortisol measurements and clinical presentation; 9/22 cases had undiagnosed hypopituitarism; 13/22 patients had secondary adrenal insufficiency due to exogenous steroid administration.

Conclusions

In a large, prospective and well‐defined cohort of euvolaemic hyponatraemia, undiagnosed secondary adrenal insufficiency co‐occurred in 3·8% of cases initially diagnosed as SIAD. Undiagnosed pituitary disease was responsible for 1·5% of cases presenting as euvolaemic hyponatraemia.
Risk, resilience and identity construction in the life narratives of young people leaving residential care
Authors: Schofield Gillian , Larsson Birgit , Ward Emma
Published: June 2016

The role of residential care for children has developed very differently internationally, but in all cultural contexts, there are questions about the extent to which it can help young people recover from high risk backgrounds. In the UK, residential care has come to be seen as the placement of last resort, yet new government guidance on permanence has suggested that residential care can provide security and a sense of belonging. Narrative analysis of interviews with 20 care leavers identified their different pathways from birth families through residential care to early adulthood. Some experienced a transformation from a negative sense of self as victims or ‘bad children’ to survivors, while others continued to struggle. Key to successful turning points were four interacting factors, all associated with resilience; connection, agency, activity and coherence. These narratives revealed the importance of nurturing relationships and a sense of ‘family’, and also the role of support after leaving residential care, when transitions workers helped them to move on but stay connected. The study highlighted how residential care leavers from adverse backgrounds attribute very different meanings to their experiences, which affects identity construction, resilience and the need for support.
When to suspect tinea; a histopathologic study of 103 cases of PAS‐positive tinea
Authors: Elbendary Amira , Valdebran Manuel , Gad AbdAllah , Elston Dirk M.
Published: June 2016

Background

The histopathologic features of tinea vary widely and its diagnosis could be easily missed if the index of suspicion is not high. We aimed in this study to detect histopathologic features that could be a clue for diagnosis

Methods

We retrospectively reviewed 103 cases of tinea, confirmed by Periodic acid–Schiff (PAS) staining. For each case, gender, biopsy site, and pre‐biopsy suspicion were recorded. The presence or absence of 17 microscopic features was noted.

Results

Concordance between pre‐biopsy and histopathologic diagnosis was noted in 57.28% of cases, suggesting that the diagnosis is often not suspected clinically. Among the histopathologic features studied, a compact stratum corneum (either uniform or forming a layer beneath a basket weave stratum corneum), parakeratosis, mild spongiosis and neutrophils in the stratum corneum and within the blood vessels were the most frequent features noted.

Conclusion

This study suggests histopathologic clues that should prompt the pathologist to order a PAS stain, especially when diagnosis is not suspected clinically.
Ataxia telangiectasia: a syndrome deserving attention and study
Authors: Capra Sandra
Published: June 2016

This commentary is on the original article by Lefton‐Greif et al. on pages 1069–1075 of this issue.
Addition of sulphonylurea to metformin does not relevantly change body weight: a prospective observational cohort study (ZODIAC‐39)
Authors: Schrijnders Dennis , Wever Raiza , Kleefstra Nanne , Houweling Sebastiaan T. , van Hateren Kornelis J. J. , de Bock Geertruida H. , Bilo Henk J. G. , Groenier Klaas H. , Landman Gijs W. D.
Published: June 2016

Aim

To investigate changes in body weight trajectories after the addition of individual sulphonylureas (SUs) to metformin in patients with type 2 diabetes.

Materials and methods

We conducted a retrospective observational cohort study, in a primary care setting in the Netherlands. Patients aged ≥18 years with type 2 diabetes who were included in the ZODIAC cohort between 1998 and 2012 and who received metformin monotherapy at inclusion (n = 29 195), and had used metformin as monotherapy for at least 1 year before receiving dual therapy through the addition of an SU for at least 1 year were eligible for inclusion. The primary outcome was within‐drug yearly change in body weight after receiving add‐on therapy with individual SUs during 5 years of follow‐up. The secondary outcome was within‐drug yearly change in glycated haemoglobin (HbA1c). Annual changes in weight and HbA1c were estimated with linear mixed models, adjusted for age, gender and diabetes duration.

Results

A total of 2958 patients were included. No significant weight changes were observed within and between any of the individual SUs after treatment intensification (p = 0.24). In addition, no significant difference in weight between the add‐on therapy combinations was observed (p = 0.26). The average HbA1c the year before intensification was 7.2% (55 mmol/mol) and dropped below 7.0% (53 mmol/mol) the year after.

Conclusions

In patients with type 2 diabetes treated in primary care, strict glycaemic control can be maintained with SUs used as add‐on therapy to metformin, without the offset of relevant weight changes.
Effect of testosterone on insulin sensitivity, oxidative metabolism and body composition in aging men with type 2 diabetes on metformin monotherapy
Authors: Magnussen Line V. , Glintborg Dorte , Hermann Pernille , Hougaard David M. , Højlund Kurt , Andersen Marianne
Published: June 2016

Aims

To evaluate the effect of testosterone replacement therapy (TRT) on body composition, insulin sensitivity, oxidative metabolism and glycaemic control in aging men with lowered bioavailable testosterone (BioT) levels and type 2 diabetes mellitus (T2D) controlled on metformin monotherapy.

Materials and methods

We conducted a randomized, double‐blind, placebo‐controlled study in 39 men aged 50‐70 years with BioT levels <7.3 nmol/L and T2D treated with metformin monotherapy. Patients were randomized to testosterone gel (TRT, n = 20) or placebo (n = 19) for 24 weeks. Lean body mass (LBM), total and regional fat mass were measured using whole‐body dual‐energy X‐ray absorptiometry scans. Whole‐body peripheral insulin sensitivity, endogenous glucose production (EGP) and substrate oxidation were assessed by euglycaemic‐hyperinsulinaemic clamp with glucose tracer and combined with indirect calorimetry. Coefficients (β) represent the placebo‐controlled mean effect of intervention.

Results

LBM (β = 1.9 kg, p = 0.001) increased after TRT, while total fat mass (β = −1.3 kg, p = 0.009), fat mass trunk (β = −0.7 kg, p = 0.043), fat mass legs (β = −0.7 kg, p = 0.025), fat mass arms (β = −0.3 kg, p = 0.001), and HDL cholesterol (β = −0.11 mmol/L, p = 0.009) decreased after TRT compared with placebo. Insulin‐stimulated glucose disposal rates did not change in response to TRT compared with placebo (p = 0.18). Moreover, glycated haemoglobin, and basal and insulin‐stimulated rates of EGP, lipid‐ and glucose‐oxidation were unaltered after TRT.

Conclusion

TRT in aging men with lowered BioT levels and T2D controlled on metformin monotherapy improved body composition; however, glycaemic control, peripheral insulin sensitivity, EGP and substrate metabolism were unchanged.
Pericardial effusion due to cholesterol pericarditis in case of rheumatoid arthritis
Authors: Gecmen Cetin , Gecmen Gonca Gul , Kahyaoglu Muzaffer , Ece Dilek , Ozkan Birol , Karaman Ozge , Naser Abdurrahman , Kalayci Arzu , Karabay Can Yucel , Kirma Cevat
Published: June 2016

Mini‐Abstract

A 53‐year‐old male patient with a history of rheumatoid arthritis presented with exertional dyspnea, abdominal distension, and pleuritic chest pain for approximately one month. Transthoracic echocardiography revealed a large, hyperechogenic, and circumferential pericardial effusion. The computer tomography revealed circumferential hyperdense fluid image around the heart. After that findings, we aspirated approximately 900 mL yellow fluid with gold paint by emergency pericardial tapping with transthoracic echocardiographic guidance. Cytopathologic examination of the pericardial effusion showed the presence of multinucleated giant cells. The pathological images revealed rare crystals of cholesterol which were engulfed by multinucleated giant cells. The gold‐paint appearance, high cholesterol content, and cytopathologic characteristics of the pericardial effusion supported the diagnosis of cholesterol pericarditis.
The interconnected rhizosphere: High network complexity dominates rhizosphere assemblages
Authors: Shi Shengjing , Nuccio Erin E. , Shi Zhou J. , He Zhili , Zhou Jizhong , Firestone Mary K.
Published: June 2016

While interactions between roots and microorganisms have been intensively studied, we know little about interactions among root‐associated microbes. We used random matrix theory‐based network analysis of 16S rRNA genes to identify bacterial networks associated with wild oat (Avena fatua) over two seasons in greenhouse microcosms. Rhizosphere networks were substantially more complex than those in surrounding soils, indicating the rhizosphere has a greater potential for interactions and niche‐sharing. Network complexity increased as plants grew, even as diversity decreased, highlighting that community organisation is not captured by univariate diversity. Covariations were predominantly positive (> 80%), suggesting that extensive mutualistic interactions may occur among rhizosphere bacteria; we identified quorum‐based signalling as one potential strategy. Putative keystone taxa often had low relative abundances, suggesting low‐abundance taxa may significantly contribute to rhizosphere function. Network complexity, a previously undescribed property of the rhizosphere microbiome, appears to be a defining characteristic of this habitat.
Monitoring chromosomal polymorphism in Drosophila subobscura over 40 years
Authors: Orengo Dorcas J. , Puerma Eva , Aguadé Montserrat
Published: June 2016

The inversion chromosomal polymorphism of Drosophila subobscura is considered to be adaptive as a result of its responses at different time scales to temperature changes. This work reports the longest‐term study of chromosomal polymorphism for a single population of D. subobscura with climatic data from the collecting site itself. The chromosomal analysis of D. subobscura samples collected six times over a 40‐year period at the same location and in the same seasonal interval has revealed the continuous presence of 16 common and six moderately rare chromosomal arrangements through the period. This analysis also corroborates the previously detected negative relationship between the frequencies of the standard (cold‐climate) arrangement on each of its five chromosomes and temperature, as well as between a comprehensive measure of cold adaptation (the total autosomal proportion of standard arrangement) and temperature. These and previous results would support that species harboring cold‐ and warm‐adapted polymorphic chromosomal arrangements, like D. subobscura, can rapidly respond to environmental changes.
Drug‐resistant epilepsy in adults: Outcome trajectories after failure of two medications
Authors: Choi Hyunmi , Hayat Matthew J. , Zhang Ruiqi , Hirsch Lawrence J. , Bazil Carl W. , Mendiratta Anil , Kato Kenneth , Javed Asif , Legge Alexander W. , Buchsbaum Richard , Resor Stanley , Heiman Gary A.
Published: June 2016

Objective

To examine the seizure trajectories of adults with epilepsy developing drug‐resistant epilepsy (DRE) and to identify the predictors of seizure trajectory outcome.

Methods

Adult patients failing two antiepileptic drugs (AEDs) due to inefficacy and starting their third AED at a tertiary epilepsy center were followed for seizure trajectory outcome during medical management. Seizure trajectories were categorized into one of four patterns: (1) course with constant seizures; (2) fluctuating course; (3) delayed attainment of seizure freedom (seizure freedom delayed for >12 months after start of the study, but patient stayed in seizure freedom); and (4) early attainment of seizure freedom (within 12 months of starting study). Multiple ordinal logistic regression models were used to estimate the association between trajectory categories and clinical factors.

Results

Four hundred three adult patients met the eligibility criteria. Of these, 212 (53%) never achieved a seizure‐free period of a year or more. The trajectories of 63 patients (16%) had a complex fluctuating trajectory, 62 (15%) had delayed onset of seizure freedom, and 66 (16%) had an early seizure freedom. Independent predictors associated with more favorable outcome trajectories were epilepsy type and length of follow‐up. Specifically, compared to patients with focal epilepsy of temporal lobe, patients with focal epilepsy of occipital lobe (OR 3.80, 95% confidence interval [CI] 1.00–14.51, p = 0.04), generalized genetic (OR 3.23, 95% CI 1.88–5.57, p < 0.0001), unclear epilepsy type (OR 3.82, 95% CI 1.53–9.52, p < 0.005), and both focal and generalized epilepsy(OR 11.73, 95% CI 1.69–81.34, p = 0.01) were significantly more likely to experience a better trajectory pattern.

Significance

Examination of patterns of seizure trajectory of patients with incident DRE showed that 31% were in continuous seizure freedom at the end of the observation period.
Safety, tolerability, and seizure control during long‐term treatment with adjunctive brivaracetam for partial‐onset seizures
Authors: Toledo Manuel , Whitesides John , Schiemann Jimmy , Johnson Martin E. , Eckhardt Klaus , McDonough Belinda , Borghs Simon , Kwan Patrick
Published: June 2016

Objectives

To report pooled safety/tolerability and seizure outcome data from adults with uncontrolled partial‐onset (focal) seizures (POS) receiving adjunctive brivaracetam (BRV) during phase IIb/III and long‐term follow‐up (LTFU) studies.

Methods

Seizure outcome data were pooled from phase IIb (NCT00175929 and NCT00175825), III/IIIb (NCT00490035, NCT00464269, NCT00504881, and NCT01261325) and associated LTFU studies (NCT00175916, NCT00150800, and NCT01339559). Safety/tolerability data were pooled from these studies plus NCT01405508, NCT01653262, and NCT01728077 (LTFU). Patients received placebo (during core studies) or BRV 5–200 mg/day. Safety/tolerability and seizure outcomes (BRV modal doses 50–200 mg/day) were assessed until January 17, 2014.

Results

Of 2,186 patients (97.3% with POS and 2.7% with other seizure types) who received BRV 50–200 mg/day, 2,051 (93.8%) completed core studies and continued in LTFU studies. Total BRV exposure: 5,339.4 patient‐years (≥8.0 years in 41 patients); 6‐, 12‐, 24‐, and 60‐month retention: 91.0%, 79.8%, 68.1%, and 54.4%, respectively. Safety/tolerability data pooled from 2,186 patients: ≥1 treatment‐emergent adverse event (TEAE) reported by 1,848 (84.5%) patients; 1,184 (54.2%) reported ≥1 TEAE considered treatment‐related. Most frequent TEAEs (≥10%): headache (20.9%), dizziness (17.5%), somnolence (15.2%), nasopharyngitis (13.2%), fatigue (11.3%), and convulsion (10.6%). Serious TEAEs (SAEs) and treatment‐related SAEs: 401 (18.3%) and 95 (4.3%) patients, respectively. Of 28 (1.3%) deaths, four (14.3%) were considered possibly treatment related by the investigator. Pooled seizure outcome data (1,836 patients): median POS frequency/28 days at baseline was 8.9; on treatment, median percentage reduction from baseline in POS/28 days was 48.8%, and ≥50% responder rate was 48.7%. Complete seizure freedom: 4.9%, 4.2%, 3.0%, and 3.3% for ≥6, 12, 24, and 60 months, respectively. Improvements were seen in health‐related quality of life (HRQoL) from baseline, assessed by Quality of Life in Epilepsy Inventory‐31.

Significance

Adjunctive BRV treatment in adults with POS was effective and generally well tolerated when administered long‐term (≥8.0 years). Retention was high and HRQoL improvements were observed.
Efficacy of the epilepsy nurse: Results of a randomized controlled study
Authors: Pfäfflin Margarete , Schmitz Bettina , May Theodor W.
Published: June 2016

Objective

We investigated the efficacy of epilepsy nurses on satisfaction with counseling about epilepsy in a randomized, controlled, prospective trial.

Methods

Patients with epilepsy treated by neurologists in outpatient clinics were consecutively enrolled and randomly allocated to either the epilepsy nurse (EN) group (n = 92) or the control group (n = 95). Patients in the EN group were advised according to their needs by epilepsy nurses. The control group received routine care without additional counseling. The EN group completed the questionnaires before the first consultation (T1) and 6 months later (T2); the control group completed the questionnaires twice with an interval of 6 months. Primary outcome measure was satisfaction of patients with information and support. Secondary outcome measures were satisfaction with patient–doctor relationship, organization of treatment, epilepsy knowledge, coping, and restrictions in daily life. Anxiety and depression (Hospital Anxiety and Depression Scale) and global Quality of Life (item from QOLIE‐31) were also assessed. Statistical analysis included generalized estimating equation (GEE) and nonparametric tests.

Results

Satisfaction with information and support improved significantly in the EN group compared to the control group (GEE, interaction group × time, p = 0.001). In addition, Epilepsy Knowledge (p = 0.014) and Coping (subscale Information Seeking) (p = 0.023) improved. Increase in satisfaction with counseling was dependent on patients' needs for information and on the amount of received information (Jonckheere‐Terpstra test, p < 0.001). No differences between the groups were observed on other epilepsy‐specific scales.

Significance

A reliable questionnaire for satisfaction with epilepsy care has been developed. Epilepsy nurses improve the satisfaction of patients with counseling and information about epilepsy and concomitant problems.