bluuebunny/crossref_metadata_2025 huggingface dataset:
Abundant cytomegalovirus (CMV) reactive clonotypes in the CD8+ T cell receptor alpha repertoire following allogeneic transplantation
Authors: Link C S , Eugster A , Heidenreich F , Rücker-Braun E , Schmiedgen M , Oelschlägel U , Kühn D , Dietz S , Fuchs Y , Dahl A , Domingues A M J , Klesse C , Schmitz M , Ehninger G , Bornhäuser M , Schetelig J , Bonifacio E
Published: January 2016

Allogeneic stem cell transplantation is potentially curative, but associated with post-transplantation complications, including cytomegalovirus (CMV) infections. An effective immune response requires T cells recognizing CMV epitopes via their T cell receptors (TCRs). Little is known about the TCR repertoire, in particular the TCR-α repertoire and its clinical relevance in patients following stem cell transplantation. Using next-generation sequencing we examined the TCR-α repertoire of CD8+ T cells and CMV-specific CD8+ T cells in four patients. Additionally, we performed single-cell TCR-αβ sequencing of CMV-specific CD8+ T cells. The TCR-α composition of human leucocyte antigen (HLA)-A*0201 CMVpp65– and CMVIE-specific T cells was oligoclonal and defined by few dominant clonotypes. Frequencies of single clonotypes reached up to 11% of all CD8+ T cells and half of the total CD8+ T cell repertoire was dominated by few CMV-reactive clonotypes. Some TCR-α clonotypes were shared between patients. Gene expression of the circulating CMV-specific CD8+ T cells was consistent with chronically activated effector memory T cells. The CD8+ T cell response to CMV reactivation resulted in an expansion of a few TCR-α clonotypes to dominate the CD8+ repertoires. These results warrant further larger studies to define the ability of oligoclonally expanded T cell clones to achieve an effective anti-viral T cell response in this setting.
Low postoperative nonstimulated thyroglobulin as a criterion for the indication of low radioiodine activity in patients with papillary thyroid cancer of intermediate risk ‘with higher risk features’
Authors: Rosario Pedro Weslley , Mourão Gabriela Franco , Calsolari Maria Regina
Published: January 2016

Objective

This study evaluated low‐activity 131I therapy in patients with papillary thyroid carcinoma (PTC) of intermediate risk ‘with higher risk features’ who had low nonstimulated thyroglobulin (Tg) after thyroidectomy.

Design and Patients

This was a prospective study including 102 patients with tumours >1 cm and aggressive histology; and/or >3 positive lymph node (LN) or LN >1·5 cm or exhibiting macroscopic extracapsular extension, and clinically apparent (cN1); and/or a combination of a tumour >4 cm, microscopic extrathyroidal extension and LN metastases (cN1). After thyroidectomy, all patients had nonstimulated Tg < 0·3 ng/ml and negative antithyroglobulin antibodies (TgAb) and neck ultrasonography (US). The patients were treated with a low activity of 131I (1110 or 1850 MBq).

Results

Post‐therapy whole‐body scanning (RxWBS) showed ectopic uptake in four patients. When evaluated 12 months after 131I therapy, nonstimulated Tg ≤ 0·2 ng/ml with negative TgAb and US, defined as excellent response to initial therapy, was achieved in 101 patients (99%). Only one patient with positive initial RxWBS had structural disease. During follow‐up, four patients (4%) relapsed, including LN metastases in two, pulmonary metastases in one, and elevated Tg in one. The other 98 patients remained with nonstimulated Tg ≤ 0·2 ng/ml and negative TgAb and US. There was no case of death due to the tumour.

Conclusions

We conclude that in intermediate‐risk patients ‘with higher risk features’, low nonstimulated Tg measured with a second‐generation assay can be used as criterion for the administration of low 131I activities (1850 MBq or less).
The consequences of poaching and anthropogenic change for forest elephants
Authors: Breuer Thomas , Maisels Fiona , Fishlock Vicki
Published: January 2016

Poaching has devastated forest elephant populations (Loxodonta cyclotis), and their habitat is dramatically changing. The long‐term effects of poaching and other anthropogenic threats have been well studied in savannah elephants (Loxodonta africana), but the impacts of these changes for Central Africa's forest elephants have not been discussed. We examined potential repercussions of these threats and the related consequences for forest elephants in Central Africa by summarizing the lessons learned from savannah elephants and small forest elephant populations in West Africa. Forest elephant social organization is less known than the social organization of savannah elephants, but the close evolutionary history of these species suggests that they will respond to anthropogenic threats in broadly similar ways. The loss of older, experienced individuals in an elephant population disrupts ecological, social, and population parameters. Severe reduction of elephant abundance within Central Africa's forests can alter plant communities and ecosystem functions. Poaching, habitat alterations, and human population increase are probably compressing forest elephants into protected areas and increasing human–elephant conflict, which negatively affects their conservation. We encourage conservationists to look beyond documenting forest elephant population decline and address the causes of these declines when developing conversation strategies. We suggest assessing the effectiveness of the existing protected‐area networks for landscape connectivity in light of current industrial and infrastructure development. Longitudinal assessments of the effects of landscape changes on forest elephant sociality and behavior are also needed. Finally, lessons learned from West African elephant population loss and habitat fragmentation should be used to inform strategies for land‐use planning and managing human–elephant interactions.
Using perceptions as evidence to improve conservation and environmental management
Authors: Bennett Nathan James
Published: January 2016

The conservation community is increasingly focusing on the monitoring and evaluation of management, governance, ecological, and social considerations as part of a broader move toward adaptive management and evidence‐based conservation. Evidence is any information that can be used to come to a conclusion and support a judgment or, in this case, to make decisions that will improve conservation policies, actions, and outcomes. Perceptions are one type of information that is often dismissed as anecdotal by those arguing for evidence‐based conservation. In this paper, I clarify the contributions of research on perceptions of conservation to improving adaptive and evidence‐based conservation. Studies of the perceptions of local people can provide important insights into observations, understandings and interpretations of the social impacts, and ecological outcomes of conservation; the legitimacy of conservation governance; and the social acceptability of environmental management. Perceptions of these factors contribute to positive or negative local evaluations of conservation initiatives. It is positive perceptions, not just objective scientific evidence of effectiveness, that ultimately ensure the support of local constituents thus enabling the long‐term success of conservation. Research on perceptions can inform courses of action to improve conservation and governance at scales ranging from individual initiatives to national and international policies. Better incorporation of evidence from across the social and natural sciences and integration of a plurality of methods into monitoring and evaluation will provide a more complete picture on which to base conservation decisions and environmental management.
Personalized medicine in diabetes: the role of ‘omics’ and biomarkers
Authors: Pearson E. R.
Published: January 2016

Personalized medicine, otherwise called stratified or precision medicine, aims to better target intervention to the individual to maximize benefit and minimize harm. This review discusses how diabetes aetiology, pathophysiology and patient genotype influence response to or side effects of the commonly used diabetes treatments. C‐peptide is a useful biomarker that is underused to guide treatment choice, severe insulin deficiency predicts non‐response to glucagon‐like peptide‐1 receptor agonists, and thiazolidinediones are more effective in insulin‐resistant patients. The field of pharmacogenetics is now yielding clinically important results, with three examples outlined: sulphonylurea sensitivity in patients with HNF1A maturity‐onset diabetes of the young; sulphonylurea sensitivity in patients with Type 2 diabetes with reduced function alleles at CYP2C9, resulting in reduced metabolism of sulphonylureas; and severe metformin intolerance associated with reduced function organic cation transporter 1 (OCT1) variants, exacerbated by drugs that also inhibit OCT1. Genome‐wide approaches and the potential of other ‘omics’, including metagenomics and metabolomics, are then outlined, highlighting the complex interacting networks that we need to understand before we can truly personalize diabetes treatments.
DPD epitope‐specific glutamic acid decarboxylase (GAD)65 autoantibodies in children with Type 1 diabetes
Authors: Bansal N. , Hampe C. S. , Rodriguez L. , O'Brian Smith E. , Kushner J. , Balasubramanyam A. , Redondo M. J.
Published: January 2016

Aim

To study whether DPD epitope‐specific glutamate decarboxylase autoantibodies are found more frequently in children with milder forms of Type 1 diabetes.

Methods

We prospectively evaluated 75 children with new‐onset autoimmune Type 1 diabetes, in whom we collected demographic, anthropometric and clinical data and measured islet autoantibodies. Glutamate decarboxylase 65 autoantibody‐positive samples were analysed for epitope specificities using recombinant Fab against the DPD‐defined epitope of glutamate decarboxylase 65.

Results

After adjustment for age, positive DPD epitope recognition was significantly associated with higher C‐peptide levels at onset (P = 0.02, r2=0.21, n = 35), and high DPD recognition in the highest quartile tended to be associated with HbA1c ≤ 53 mmol/mol (7%) at the last follow‐up [mean (sd) follow‐up 1.3 (0.4) years; P = 0.07; for the model, P = 0.044, n = 30)]. Age‐ and sex‐adjusted BMI percentile was significantly correlated with recognition of the DPD‐defined epitope (P < 0.03, r2=0.14, n = 34), but this correlation was driven by the older age group (age ≥ 10 years; P = 0.016, r2=0.27, n = 21) and was not significant in younger children (P = 0.93, n = 13). There were no independent associations with sex, race/ethnicity, diabetic ketoacidosis, HbA1c, HLA DR3‐DQ2/DR4‐DQ8 or autoantibody number.

Conclusions

Our findings suggest that recognition of the DPD‐defined glutamate decarboxylase 65 autoantibody epitope at Type 1 diabetes onset is directly associated with β‐cell function, BMI and age, which supports the hypothesis that immunological factors contribute to the clinical heterogeneity of Type 1 diabetes. Larger studies relating epitope‐specific glutamate decarboxylase 65 autoantibody to clinical phenotype in children with Type 1 diabetes are warranted.
Young people with Type 1 diabetes of non‐white ethnicity and lower socio‐economic status have poorer glycaemic control in England and Wales
Authors: Khanolkar A. R. , Amin R. , Taylor‐Robinson D. , Viner R. M. , Warner J. T. , Stephenson T.
Published: January 2016

Background

The impact of ethnicity and socio‐economic status (SES) on glycaemic control during childhood Type 1 diabetes is poorly understood in England and Wales.

Methods

We studied 18 478 children with Type 1 diabetes (< 19 years) attending diabetes clinics and included in the 2012–2013 National Paediatric Diabetes Audit. Self‐identified ethnicity was categorized as white, Asian, black, mixed, other and ‘not‐stated’ (did not to divulge ethnicity). A small area measure of SES was estimated from the Index of Multiple Deprivation. Multiple linear regression was used to assess associations between ethnicity, SES and glycaemic control (mean HbA1c levels) accounting for age, gender and diabetes duration. The impact of insulin pump use on the ethnicity/SES–HbA1c associations was tested in 13 962 children.

Results

All children from minority ethnic groups had higher mean HbA1c compared with white children, with largest differences observed in black and mixed ethnicities [8 mmol/mol (2.9%), 95% CI 5–11 and 7 mmol/mol (2.8%), 95% CI 5–9, respectively]. Lower SES was associated with higher mean HbA1c with a dose effect. The lowest SES group had a mean HbA1c that was 7 mmol/mol (2.8%) (95% CI 6–8) higher compared with the highest SES group, adjusted for ethnicity. Estimates for ethnicity were attenuated, but significant on adjustment for SES. Fewer non‐white (white 20.3 vs. black 5.5%) and deprived (least deprived 21.1 vs. most deprived 13.2%) children were on insulin pump therapy. Ethnicity and SES remained significant predictors of HbA1c after accounting for insulin pump use.

Conclusion

The association between ethnicity and glycaemic control persists after adjustment for deprivation and pump use. An alternative approach to intensive insulin therapy might benefit these vulnerable children.
Guidelines for managing diabetes in Ramadan
Authors: Ali S. , Davies M. J. , Brady E. M. , Gray L. J. , Khunti K. , Beshyah S. A. , Hanif W.
Published: January 2016

Background

Globally there are approximately 90 million Muslims with diabetes of which approximately 400 000 reside within the UK. The holy month of Ramadan is a fundamental practice of this religion of which fasting from sun‐rise to sun‐set is an integral part. This poses many potential risks for those with diabetes who wish to observe Ramadan.

Methods

The evidence base for best clinical management of Type 1 and Type 2 diabetes during Ramadan was reviewed. We reviewed current and previous recommendations for safe fasting during Ramadan.

Results

The risks associated with fasting in those with diabetes and preparing your patient for Ramadan are discussed. We have reviewed the evidence around diet‐controlled diabetes and therapies including; metformin, acarbose, metglitinides, sulfonylureas, thiazolidinidiones, dipeptidyl peptidase‐4 inhibitor (DPP‐4), sodium glucose co‐transporter ‐2 (SGLT‐2) inhibitors, glucagon‐like peptide ‐1 (GLP‐1) receptor agonists and insulin.

Conclusion

Up to date guidelines for the management of treatment regimes are set‐out for those with Type 1 and Type 2 diabetes who wish to fast during Ramadan.
When's dinner? Does timing of dinner affect the cardiometabolic risk profiles of South‐Asian Canadians at risk for diabetes
Authors: Sandhu S. K. , Tang T. S.
Published: January 2016

Aim

To explore the relationship between the time dinner is consumed (dinnertime or timing of dinner) and cardiometabolic risk factors among South‐Asian Canadians at risk for diabetes.

Methods

We recruited 432 South‐Asian adults affiliated with Sikh and Hindu Temples in Metro Vancouver. Participants deemed to be at risk of diabetes underwent a clinical and behavioural assessment. Dinnertime was measured via self‐report. Clinical endpoints included HbA1c, apolipoprotein, blood pressure, weight, BMI and waist circumference.

Results

The mean age of participants was 65 years and 59% were male. Dinnertime was categorized into three groups: early (before 18:00 h); average (18:00 to 20:00 h); and late (later than 20:00 h). Among the participants, 19% (n = 79), 44% (n = 187) and 37% (n = 157) reported early, average and late dinnertimes, respectively. Significant differences were found for dinnertime groups and years of residence in Canada, gender and employment. Compared with the early dinnertime group, the late dinnertime group lived in Canada for a shorter duration, comprised a higher proportion of males (66 vs 48%; P = 0.01) and were currently employed (37 vs 22%; P = 0.02). With regard to clinical endpoints, compared with the early dinnertime group, the late dinnertime group had lower systolic blood pressure (135.9 vs 131.7 mmHg; P = 0.03). After controlling for demographic characteristics, this difference was diminished. No significant differences were found between dinnertime and HbA1c, apolipoprotein, diastolic blood pressure, weight, BMI and waist circumference.

Conclusion

Findings suggest that, among this sample of South‐Asian Canadians at risk of Type 2 diabetes, there was no association between timing of the evening meal and cardiometabolic profiles.
Factors associated with early insulin initiation in Type 2 diabetes: a Canadian cross‐sectional study
Authors: Abu‐Ashour W. , Chibrikova L. , Midodzi W. K. , Twells L. K. , Gamble J.‐M.
Published: January 2016

Aim

To examine the patient characteristics associated with early initiation of insulin after a diagnosis of Type 2 diabetes.

Methods

We analysed cross‐sectional data from the 2012 Canadian Community Health Survey conducted by Statistics Canada. Multivariable logistic regression was used to explore the association between patient sociodemographic and health status characteristics and initiating insulin within 1 year of a diagnosis of Type 2 diabetes (early insulin use).

Results

Weighted estimates for the Canadian population showed that 32% of patients with Type 2 diabetes initiated insulin within 1 year of their diagnosis. Of the insulin initiators, 52% were female and 68% were aged ≥60 years. Factors strongly associated with early initiation of insulin were age (60–69 years: adjusted odds ratio 1.89, 95% CI 1.84–1.94; ≥ 70 years, odds ratio 2.08, 95% CI 2.01–2.15, both vs 40–49 years); smoking (smoker vs never: odds ratio 2.39, 95% CI 2.32–2.46); geography (Western Canada: odds ratio 2.75, 95% CI 2.69–2.81; Quebec: odds ratio 2.20, 95% CI 2.13–2.27, both vs Ontario); mental health (poor vs excellent: odds ratio 1.98, 95% CI 1.92–2.04); BMI (overweight vs normal/underweight: odds ratio 1.63, 95% CI 1.58–1.67); oral antidiabetic medication use (yes vs no: odds ratio 0.66, 95% CI 0.65–0.68); and alcohol use (regular vs non‐drinker: odds ratio 0.66, 95% CI 0.65–0.68).

Conclusion

One‐third of the study population with Type 2 diabetes initiated insulin within their first year of diagnosis. Age, smoking status, geographical location, mental health, BMI, education, oral antidiabetic medication use, employment, physical activity, language, doctor visits and alcohol consumption were associated with timing of insulin initiation.
The early recognition inventory ERIraos assesses the entire spectrum of symptoms through the course of an at‐risk mental state
Authors: Maurer Kurt , Zink Mathias , Rausch Franziska , Häfner Heinz
Published: January 2016

Aim

Functional disability and social consequences frequently occur at the prodromal stage of schizophrenia. Efforts to recognize an increasing risk of psychosis onset have thus become a topical issue worldwide. This is to introduce the English version of the ERIraos early‐recognition inventory.

Methods

The ERIraos, developed in a systematic, empirical approach from the Instrument for the Retrospective Assessment of the Onset of Schizophrenia, incorporates basic symptoms from the Cologne Early Recognition Study. The research version also includes as further predictive items so‐called brief limited intermittent psychotic symptoms and attenuated psychotic symptoms from the Comprehensive Assessment of At‐Risk Mental States instrument.

Results

The ERIraos with its 15‐item screening Checklist and 50‐item Symptom List permits early recognition of psychosis risk in three steps of decreasing sensitivity and increasing specificity. Step 1 relies on patients’ self‐perception of symptoms, which prompt them to contact a primary health service. There, in Step 2, at‐risk individuals are identified using the Checklist, characterized by a low‐risk threshold, and referred to further examination using the Symptom List (Step 3). Information on symptom accumulation and increasing symptom severity enhances the instrument's predictive power. In a validation test, psychotic transitions increased linearly up to 50% over 2 years. Compared with other instruments and on the prodromal stage of depressive disorder, the ERIraos has shown good predictive capacity.

Conclusions

The ERIraos has been successfully employed as a two‐step tool for the early recognition of psychosis risk in several German studies and translated into several foreign languages.
Expressed emotion and the escalation of depressive symptoms in individuals with recent‐onset schizophrenia
Authors: Rosenfarb Irwin Ford , Triana Stephanie , Nuechterlein Keith H. , Ventura Joseph , Breitborde Nicholas J.K.
Published: January 2016

Aim

This study examined whether expressed emotion (EE) predicts the emergence of depressive symptoms over a 1‐year period in 109 individuals with recent‐onset schizophrenia.

Methods and Results

Cox proportional hazards regression analyses indicated that EE did not predict the emergence of depressive symptoms. The results also indicated that the EE factors (criticism, hostility and emotional overinvolvement), when examined individually, also did not predict the emergence of depressive symptoms.

Conclusions

Given the large number of patients in the study who were followed up for 1 year and another study's finding, using a subset of patients from the current study, of a significant relationship between EE and psychotic relapse, the data suggest that whereas EE is related to both psychotic relapse in individuals with recent‐onset schizophrenia and depressive relapse in individuals with major depressive disorder, EE does not appear to predict depressive exacerbation in individuals with recent‐onset schizophrenia.
Prolonged duration of untreated psychosis: a problem that needs addressing
Authors: Cotter Jack , Zabel Elisabeth , French Paul , Yung Alison R.
Published: January 2016

Aim

The duration of untreated psychosis (DUP) refers to the period of time between the emergence of psychotic symptoms and the initiation of appropriate clinical treatment. Prolonged DUP is associated with a range of adverse consequences, including more severe illness course, cognitive deficits and poor functioning. Problems with recognition of illness and in seeking help contribute to DUP, but another major cause of prolonged DUP is delays within secondary mental health services. In an attempt to reduce these delays, National Health Service England and the Department of Health have set new targets to improve access to early intervention services which will come into effect in April 2016. Given this background, we aimed to examine the DUP and pathways to care of new patients entering an early intervention service. We also examined whether they were receiving National Institute for Health and Care Excellence (NICE) concordant treatment. This will enable us to establish a baseline so that the impact of the new targets can be determined and to assess the degree of change that will be required to implement these.

Methods

De‐identified electronic records of 165 patients accepted into the service over a 12‐month period were analysed.

Results

Median DUP was 6 months. There was a median of 2 contacts prior to service entry. Community Mental Health Teams were the largest source of referrals.

Conclusions

The majority of patients had a DUP exceeding the international target of 3 months. The findings appear to support previous evidence that this may be partially attributable to significant delays within the mental health care system.
Relation between premorbid adjustment, duration of untreated psychosis and close interpersonal trauma in first‐episode psychosis
Authors: Haahr Ulrik Helt , Larsen Tor Ketil , Simonsen Erik , Rund Bjørn Rishovd , Joa Inge , Rossberg Jan Ivar , Johannessen Jan Olav , Langeveld Johannes , Evensen Julie , Trauelsen Anne Marie Hyldgaard , Vaglum Per , Opjordsmoen Stein , Hegelstad Wenche ten Velden , Friis Svein , McGlashan Thomas , Melle Ingrid
Published: January 2016

Aim

Interpersonal traumas are highly prevalent in patients with psychotic disorders. Trauma caused by those close to the patient might have a more profound impact than other types of trauma and may influence early life social functioning. The aim is to investigate the associations between different types of trauma, in particular close interpersonal traumas experienced before the age of 18, premorbid factors and baseline clinical characteristics in a sample of first‐episode psychosis patients.

Methods

A total of 191 patients from the ‘TIPS’ cohort completed assessment with the Brief Betrayal Trauma Survey at their 5 years follow‐up interview.

Results

Half of the patients reported that they had experienced interpersonal trauma and one‐third reported having experienced close interpersonal trauma before the age of 18. Women reported more sexual abuse, physical attacks and emotional and physical maltreatment than men. There were significant associations between early interpersonal trauma and premorbid adjustment and duration of untreated psychosis, but no significant associations with length of education, comorbid substance use or baseline clinical symptomatology.

Conclusions

Close interpersonal trauma before the age of 18 is associated with poorer premorbid adjustment and a longer duration of untreated psychosis. This may indicate that traumatic experiences delay help‐seeking behaviour.
Effect of dehydration on the development of collaterals in acute middle cerebral artery occlusion
Authors: Chang S.‐W. , Huang Y.‐C. , Lin L.‐C. , Yang J.‐T. , Weng H.‐H. , Tsai Y.‐H. , Lee T.‐H.
Published: January 2016

Background and purpose

Recent large series studies have demonstrated that dehydration is common amongst stroke subjects and is associated with poor outcome. However, the effects of hydration status on the development of collaterals have never been discussed. In this study, the hypothesis that hydration status is an important factor for developing collaterals after acute middle cerebral artery (MCA) infarction was tested.

Methods

Eighty‐seven patients with acute infarction due to occlusion of the MCA were enrolled. Two collateral markers, posterior cerebral artery (PCA) laterality and fluid‐attenuated inversion recovery hyperintense vessels (HVs) were assessed from magnetic resonance imaging. Dehydration status was defined by a nitrogen to creatinine ratio ≧ of 15. The associations between dehydration status and the development of collaterals were estimated.

Results

Sixty‐one of 87 patients (70.1%) were identified as dehydrated. The development of PCA laterality and HVs shows a significant difference between dehydrated and euhydrated patients. A serum nitrogen to creatinine ratio <15, diastolic blood pressure and the presence of a dense MCA on computed tomography were significantly associated with the development of PCA laterality. A serum nitrogen to creatinine ratio <15, the initial National Institutes of Health Stroke Scale score, the presence of a dense MCA and calcifications of the internal carotid artery on computed tomography were significantly associated with the development of HVs. Dehydration remained an independent negative predictor for the development of PCA laterality and HVs in the multivariate analysis.

Conclusions

Hydration status is associated with the development of collateral flow after acute MCA occlusion. This preliminary study provides an imaging clue that hydration status and early hydration therapy could be important for acute stroke management.
Inhibition of the contralesional dorsal premotor cortex improves motor function of the affected hand following stroke
Authors: Lüdemann‐Podubecká J. , Bösl K. , Nowak D. A.
Published: January 2016

Background and purpose

Numerous studies have shown that repetitive transcranial magnetic stimulation (rTMS) over the primary motor cortex (M1) may improve motor function of the affected hand after stroke. The effects of 1 Hz rTMS applied over the contralesional dorsal premotor cortex (PMd) on hand function and cortical neurophysiology in subacute stroke were examined.

Methods

Ten subacute stroke patients with mild hand motor impairment were enrolled in a prospective, double‐blind, randomized, placebo‐controlled, crossover study with two intervention sessions. 1 Hz rTMS was applied over the contralesional PMd (real rTMS, 900 pulses at 110% of the motor threshold; sham rTMS, 900 pulses at 0% of the motor threshold). Tests of hand function (Jebsen‐Taylor hand function test, box and block test) and neurophysiological evaluations (resting motor threshold, motor evoked potentials, cortical silent period, ipsilateral silent period) were obtained from both hands and hemispheres prior to (baseline) and after each treatment.

Results

Hand function tests revealed significant improvement of motor function of the affected but not of the unaffected hand after real rTMS only. Neither intervention changed the neurophysiological measures in comparison to baseline.

Conclusion

One hertz rTMS over the contralesional PMd improves motor function of the affected hand in subacute stroke. The PMd may be a novel rTMS target to treat motor impairment after stroke.
Environmental Factors Associated With Natural Methane Occurrence in the Appalachian Basin
Authors: Molofsky Lisa J. , Connor John A. , McHugh Thomas E. , Richardson Stephen D. , Woroszylo Casper , Alvarez Pedro J.
Published: January 2016

The recent boom in shale gas development in the Marcellus Shale has increased interest in the methods to distinguish between naturally occurring methane in groundwater and stray methane associated with drilling and production operations. This study evaluates the relationship between natural methane occurrence and three principal environmental factors (groundwater redox state, water type, and topography) using two pre‐drill datasets of 132 samples from western Pennsylvania, Ohio, and West Virginia and 1417 samples from northeastern Pennsylvania. Higher natural methane concentrations in residential wells are strongly associated with reducing conditions characterized by low nitrate and low sulfate ([NO3−] < 0.5 mg/L; [SO42−] < 2.5 mg/L). However, no significant relationship exists between methane and iron [Fe(II)], which is traditionally considered an indicator of conditions that have progressed through iron reduction. As shown in previous studies, water type is significantly correlated with natural methane concentrations, where sodium (Na) ‐rich waters exhibit significantly higher (p<0.001) natural methane concentrations than calcium (Ca)‐rich waters. For water wells exhibiting Na‐rich waters and/or low nitrate and low sulfate conditions, valley locations are associated with higher methane concentrations than upland topography. Consequently, we identify three factors (“Low NO3− & SO42−” redox condition, Na‐rich water type, and valley location), which, in combination, offer strong predictive power regarding the natural occurrence of high methane concentrations. Samples exhibiting these three factors have a median methane concentration of 10,000 µg/L. These heuristic relationships may facilitate the design of pre‐drill monitoring programs and the subsequent evaluation of post‐drill monitoring results to help distinguish between naturally occurring methane and methane originating from anthropogenic sources or migration pathways.
Prognostic value of tumour deposit and perineural invasion status in colorectal cancer patients: a SEER‐based population study
Authors: Mayo Erin , Llanos Adana A M , Yi Xianghua , Duan Sheng‐Zhong , Zhang Lanjing
Published: January 2016

Aims

The definition of tumour deposit (TD) in colorectal cancer (CRC) was changed recently in the American Joint Commission on Cancer (AJCC) Staging Manual, 7th edition. We aimed to examine the prognostic values of the newly defined TD and perineural invasion (PNI) in this population study.

Methods and results

We identified the incidental CRC cases with known TD or PNI status in the Surveillance, Epidemiology, and End Results (SEER) programme diagnosed in 2010 and 2011. Kaplan–Meier survival analysis and multivariable Cox proportional hazards models were used to estimate overall survivals (OS) and cancer‐specific survival (CSS). We found that 6.71% (2774 of 41 323) of the CRC cases were positive for TD and 9.61% (3970 of 41 215) positive for PNI. In multivariable models, TD‐ and PNI‐positive statuses correlated independently with worse 3‐year OS [hazard ratio (HR): 1.68, 95% confidence interval (CI): 1.58–1.80 and HR: 1.24, 95%: CI: 1.16–1.32, respectively] and 3‐year CSS (HR: 1.79, 95% CI: 1.65–1.94 and HR: 1.28, 95% CI: 1.18–1.38, respectively, P < 0.001 for all). Other independent prognostic factors included age, T category, N category, tumour location and tumour grade, but not gender. TD and PNI correlated with worse OS in all N categories (P < 0.001 for all). TD‐associated HR for 3‐year OS increases as the N category becomes lower (1.73 in N2, 2.32 in N1 and 3.24 in N0), while rare (1.4%) TD‐positive CRC in N0 category should have been assigned to N1c.

Conclusions

Tumour deposit and PNI correlate independently with worse 3‐year OS and CSS. TD appears prognostically more important in the CRC of lower N categories.
The Separation of Indium and Copper from Spent Cu‐In Targets
Authors: Chen Wei‐sheng , Huang Shu‐mei
Published: January 2016

Nowadays, the CIGS solar cells produced process, only 30% of the original target material is used, while the rest 70% need to be recycled in order to achieve the resources sustainable. Common methods to separate and recover indium include precipitation, solvent extraction, ion‐exchange, and electrolytic processes. This research is to investigate the recovery and purification of indium from spent sputtering targets so that the recovered and purified indium can be reused in the thin film and semiconductor industries. The processes selected include ion‐exchange resin, solvent extraction, and zone refining. Eventually, indium recovery using ion exchange and solvent extraction has high recoveries. Further purification was conducted by electrowinning and zone refining process. The indium product of zone refining can be used as raw material of indium sputtering target.
Beauty, Tragedy and New Creation: Theology and Contemplation in Cappadocian Cosmology
Authors: Blowers Paul M.
Published: January 2016

This article explores whether we can speak of an aggregate Christian cosmology or doctrine of creation constructed by the Cappadocian Fathers, Basil of Caesarea, Gregory Nazianzen and Gregory of Nyssa. While discouraging the possibility of identifying a perfectly contoured ‘system’ of Cappadocian cosmology, I argue that there are certain ‘first principles’ and doctrinal correlates shared by this triumvirate. More helpful is to approach their constructive theology of creation from the standpoint of its basic epistemological protocols of theologia, which lay down the ground rules for Christian language of Creator and creation, and theôria, the church's ‘sanctified intuition’ of the meaning of the world. Theôria, as ‘contemplation’ in the broadest sense, enables the Cappadocians to envision the world, through the lens of sacred history, as a theatre of tragedy and beauty, and as the matrix of the triune Creator's aspiration to bring about an ever‐renewed creation.
‘The Body of Christ is Made From Bread’: Transubstantiation and the Grammar of Creation
Authors: Bauerschmidt Frederick Christian
Published: January 2016

Aquinas's theology of Christ's eucharistic presence, often identified by the term ‘transubstantiation’, can best be understood by locating it in relation to the ‘grammar’ of the creator–creature relationship. After a brief overview of Aquinas on creation, the article examines closely Aquinas's analysis of the statement that ‘the body of Christ is made from bread’. This allows us to begin to imagine how Aquinas might respond to one of the most influential contemporary critiques of his sacramental theology: that of Louis‐Marie Chauvet. In addition, such an examination casts new light on Aquinas's doctrine of creation itself.
Calvin's Theology of Creation and Providence: God's Care and Human Fragility
Authors: Van Der Kooi Cornelis
Published: January 2016

This article describes some of the basic elements of John Calvin's theology of creation and providence by situating them within a trinitarian framework. By using metaphors such as mirror, theatre and garment, Calvin pictured the earth as a generous gift of the Creator within which God shows his goodness, power and fatherly care. Calvin understands God not to be far away, but rather to be near and to sustain all life on earth by the power of the Holy Spirit. The visibility and tangibility of God's care as shown in the order of the universe and the reality of the world as a habitable place is of particular significance for Calvin. I argue that although contemporary science has changed our ideas regarding the universe in significant ways, there is an important aspect of Calvin's thinking that may be recognizable for the modern mind: the fragility of life on earth.
CTLA4Fcε, a novel soluble fusion protein that binds B7 molecules and the IgE receptors, and reduces human in vitro soluble CD23 production and lymphocyte proliferation
Authors: Perez‐Witzke Daniel , Miranda‐García María Auxiliadora , Suárez Nuris , Becerra Raquel , Duque Kharelys , Porras Verónica , Fuenmayor Jaheli , Montano Ramon Fernando
Published: January 2016

Immunoglobulin E‐mediated allergy and certain autoimmune diseases are characterized by the presence of a T helper type 2 (Th2) immune response and allergen‐specific or self‐reactive IgE. Soluble CD23 (sCD23) is a B‐cell factor that fosters IgE class‐switching and synthesis, suggesting that sCD23 may be a therapeutic target for these pathologies. We produced a recombinant protein, CTLA4Fcε, by fusing the ectodomain of the immunoregulatory molecule cytotoxic T‐lymphocyte antigen 4 (CTLA‐4) with a fragment of the IgE H‐chain constant region. In SDS–PAGE/inmunoblot analyses, CTLA4Fcε appeared as a 70 000 MW polypeptide that forms homodimers. Flow cytometry showed that CTLA4Fcε binds to IgE receptors FcεRI and FcεRII/CD23, as well as to CTLA‐4 counter‐receptors CD80 and CD86. Binding of CTLA4Fcε to FcεRII/CD23 appeared stronger than that of IgE. Since the cells used to study CD23 binding express CD80 and CD86, simultaneous binding of CTLA4Fcε to CD23 and CD80/CD86 seems to occur and would explain this difference. As measured by a human CD23‐specific ELISA, CTLA4Fcε – but not IgE – induced a concentration‐dependent reduction of sCD23 in culture supernatants of RPMI‐8866 cells. Our results suggest that the simultaneous binding of CTLA4Fcɛ to CD23‐CD80/CD86 may cause the formation of multi‐molecular complexes that are either internalized or pose a steric hindrance to enzymatic proteolysis, so blocking sCD23 generation. CTLA4Fcε caused a concentration‐dependent reduction of lymphocyte proliferation in human peripheral blood mononuclear cell samples stimulated in vitro with concanavalin A. The ability to bind IgE receptors on effector cells, to regulate the production of sCD23 and to inhibit lymphocyte proliferation suggests that CTLA4Fcɛ has immunomodulatory properties on human Th2 responses.
Predictors of Uncontrolled Blood Pressure in Treated Hypertensive Individuals: First Population‐Based Study in Lebanon
Authors: Farah Rita , Zeidan Rouba Karen , Chahine Mirna N. , Asmar Roland , Chahine Ramez , Salameh Pascale , Pathak Atul , Hosseini Hassan
Published: January 2016

Arterial hypertension is a leading risk factor for cardiovascular disease and stroke. This study aimed to assess the predictors of uncontrolled systolic and diastolic blood pressure (BP) in Lebanon among treated hypertensive individuals. The authors included 562 participants 40 years and older. The potential predictors included sociodemographic characteristics, self‐reported health information, and medication adherence. Prevalence of uncontrolled systolic and diastolic BP reached 43.1% and 24.9%, respectively. Independent predictors of uncontrolled systolic BP were older age, male sex, and low and medium medication adherence level. Predictors of uncontrolled diastolic BP were younger age, obesity, and low medication adherence level. Married individuals and patients taking statins had better diastolic BP control. Uncontrolled BP is a major public health problem in Lebanon. The authors identified low adherence as a major modifiable risk factor for systolic and diastolic BP control and obesity as a major modifiable risk factor for diastolic BP control.
Additive genetic variance in polyandry enables its evolution, but polyandry is unlikely to evolve through sexy or good sperm processes
Authors: Travers L. M. , Simmons L. W. , Garcia‐Gonzalez F.
Published: January 2016

Polyandry is widespread despite its costs. The sexually selected sperm hypotheses (‘sexy’ and ‘good’ sperm) posit that sperm competition plays a role in the evolution of polyandry. Two poorly studied assumptions of these hypotheses are the presence of additive genetic variance in polyandry and sperm competitiveness. Using a quantitative genetic breeding design in a natural population of Drosophila melanogaster, we first established the potential for polyandry to respond to selection. We then investigated whether polyandry can evolve through sexually selected sperm processes. We measured lifetime polyandry and offensive sperm competitiveness (P2) while controlling for sampling variance due to male × male × female interactions. We also measured additive genetic variance in egg‐to‐adult viability and controlled for its effect on P2 estimates. Female lifetime polyandry showed significant and substantial additive genetic variance and evolvability. In contrast, we found little genetic variance or evolvability in P2 or egg‐to‐adult viability. Additive genetic variance in polyandry highlights its potential to respond to selection. However, the low levels of genetic variance in sperm competitiveness suggest that the evolution of polyandry may not be driven by sexy sperm or good sperm processes.
One‐year clinical evaluation of different types of bulk‐fill composites
Authors: Bayraktar Yusuf , Ercan Ertuğrul , Hamidi Mehmet Mustafa , Çolak Hakan
Published: January 2016

Aim

In the present study, we evaluated the 1‐year clinical performance of a conventional posterior composite resin and three bulk‐fill composite resins.

Methods

Fifty patients with four class II restorations under occlusion were enrolled in the present study. A total of 200 restorations were placed in the cavity, 50 for each material (Clearfil Photo Posterior, Filtek Bulk‐Fill Flowable and Filtek P60, Tetric EvoCeram Bulk‐Fill, and SonicFill). One operator placed the restorations in the cavity, and 1 week later the patients were called for baseline examination. Two calibrated examiners evaluated the restorations once every 3 months for 1 year, according to United States Public Health Service criteria. The data were analyzed using SPSS. Non‐parametric tests (Kruskal–Wallis, Mann–Whitney U‐test, and Friedman) were used for the analysis at a confidence level of 95%.

Results

The 1‐year recall rate was 86%. All restorations showed minor modifications after 1 year. However, no statistically‐significant differences were detected between the materials’ performance at baseline and after 1 year for all criteria (P > 0.05).

Conclusions

The bulk‐fill composite resin materials showed similar clinical performance when compared with a conventional posterior composite resin. Further evaluations are necessary for the long‐term clinical performance of these materials.
Developmental alcohol exposure leads to a persistent change on astrocyte secretome
Authors: Trindade Pablo , Hampton Brian , Manhães Alex C. , Medina Alexandre E.
Published: January 2016

Fetal alcohol spectrum disorder is the most common cause of mental disabilities in the western world. It has been quite established that acute alcohol exposure can dramatically affect astrocyte function. Because the effects of early alcohol exposure on cell physiology can persist into adulthood, we tested the hypothesis that ethanol exposure in ferrets during a period equivalent to the last months of human gestation leads to persistent changes in astrocyte secretome in vitro. Animals were treated with ethanol (3.5 g/kg) or saline between postnatal day (P)10–30. At P31, astrocyte cultures were made and cells were submitted to stable isotope labeling by amino acids. Twenty‐four hour conditioned media of cells obtained from ethanol‐ or saline‐treated animals (ET‐CM or SAL‐CM) were collected and analyzed by quantitative mass spectrometry in tandem with liquid chromatography. Here, we show that 65 out of 280 quantifiable proteins displayed significant differences comparing ET‐CM to SAL‐CM. Among the 59 proteins that were found to be reduced in ET‐CM we observed components of the extracellular matrix such as laminin subunits α2, α4, β1, β2, and γ1 and the proteoglycans biglycan, heparan sulfate proteoglycan 2, and lumican. Proteins with trophic function such as insulin‐like growth factor binding protein 4, pigment epithelium‐derived factor, and clusterin as well as proteins involved on modulation of proteolysis such as metalloproteinase inhibitor 1 and plasminogen activator inhibitor‐1 were also reduced. In contrast, pro‐synaptogeneic proteins like thrombospondin‐1, hevin as well as the modulator of extracelular matrix expression, angiotensinogen, were found increased in ET‐CM. The analysis of interactome maps through ingenuity pathway analysis demonstrated that the amyloid beta A4 protein precursor, which was found reduced in ET‐CM, was previously shown to interact with ten other proteins that exhibited significant changes in the ET‐CM. Taken together our results strongly suggest that early exposure to teratogens such as alcohol may lead to an enduring change in astrocyte secretome.

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Despite efforts in prevention, fetal alcohol spectrum disorders are a major cause of mental disabilities. Here, we show that developmental exposure to alcohol lead to a persistent change in the pattern of proteins secreted (secretome) by astrocytes. This study is also the first mass spectrometry‐based assessment of the astrocyte secretome in a gyrencephalic animal.

Cover Image for this issue: doi: 10.1111/jnc.13320.