bluuebunny/crossref_metadata_2025 huggingface dataset:
Educational and rehabilitation service utilization in adolescents born preterm or with a congenital heart defect and at high risk for disability
Authors: Majnemer Annette , Dahan‐Oliel Noemi , Rohlicek Charles , Hatzigeorgiou Sean , Mazer Barbara , Maltais Desiree B , Schmitz Norbert
Published: August 2017

Aim

This historical cohort study describes the use of educational and rehabilitation services in adolescents born preterm or with a congenital heart defect (CHD).

Method

Parents of 76 young people (mean age 15y 8mo [SD 1y 8mo]) with CHD and 125 born ≤29 weeks gestational age (mean age 16y [SD 2y 5mo]) completed a demographics questionnaire including educational and rehabilitation resource utilization within the previous 6 months. Rehabilitation services included occupational therapy, physical therapy, speech language pathology, psychology. Developmental (Leiter Brief IQ, Movement‐ABC, Strengths and Difficulties Questionnaire) and functional (Vineland) status of the young people was assessed. Pearson χ2 tests were used to perform simple pairwise comparisons of categorical outcomes across the two groups (CHD, preterm). Univariate logistic regression was used to examine predictors of service utilization.

Results

Developmental profiles of the two groups (CHD/preterm) were similar (29.9%/30% IQ<80; 43.5%/50.0% motor difficulties; 23.7%/22.9% behavior problems). One‐third received educational supports or attended segregated schools. Only 16% (preterm) and 26.7% (CHD) were receiving rehabilitation services. Services were provided predominantly in the school setting, typically weekly. Few received occupational therapy or physical therapy (1.3–7.6%) despite functional limitations. Leiter Brief IQ<70 was associated with receiving educational supports (CHD: OR 5.53, 95% CI 1.29–23.68; preterm: OR 14.63, 3.10–69.08) and rehabilitation services (CHD: OR 4.46, 1.06–18.88; preterm: OR 5.11, 1.41–18.49). Young people with motor deficits were more likely to require educational (CHD: OR 5.72, 1.99–16.42; preterm: OR 3.11, 1.43–6.77) and rehabilitation services (preterm: OR 3.97, 1.21–13.03).

Interpretation

Although young people with impairments were more likely to receive educational and rehabilitation services, many may not be adequately supported, particularly by rehabilitation specialists. Rehabilitation services at this important transition phase could be beneficial in optimizing adaptive functioning in the home, school, and community.
Patterns of glycaemic control in patients with type 2 diabetes mellitus initiating second‐line therapy after metformin monotherapy: Retrospective data for 10 256 individuals from the United Kingdom and Germany
Authors: Khunti Kamlesh , Godec Thomas R. , Medina Jesús , Garcia‐Alvarez Laura , Hiller Josh , Gomes Marilia B. , Cid‐Ruzafa Javier , Charbonnel Bernard , Fenici Peter , Hammar Niklas , Hashigami Kiyoshi , Kosiborod Mikhail , Nicolucci Antonio , Shestakova Marina V. , Ji Linong , Pocock Stuart
Published: August 2017

Aim

To investigate determinants of change in glycated haemoglobin (HbA1c) in patients with type 2 diabetes mellitus (T2DM) at 6 months after initiating uninterrupted second‐line glucose‐lowering therapies.

Materials and Methods

This cohort study utilized retrospective data from 10 256 patients with T2DM who initiated second‐line glucose‐lowering therapy (switch from or add‐on to metformin) between 2011 and 2014 in Germany and the UK. Effects of pre‐specified patient characteristics on 6‐month HbA1c changes were assessed using analysis of covariance.

Results

Patients had a mean (standard error [SE]) baseline HbA1c of 8.68% (0.02); 28.5% of patients discontinued metformin and switched to an alternative therapy and the remainder initiated add‐on therapy. Mean (SE) unadjusted 6‐month HbA1c change was −1.27% (0.02). When adjusted for baseline HbA1c, 6‐month changes depended markedly on the magnitude of the baseline HbA1c (HbA1c <9%, −0.45% per unit increase in HbA1c; HbA1c ≥9%, −0.87% per unit increase in HbA1c). Adjusted mean 6‐month HbA1c reductions showed slight treatment differences (range, 0.92–1.09%; P < .001). Greater reductions in HbA1c were associated with second‐line treatment initiation within 6 months of T2DM diagnosis (1.36% vs 1.03% [P < .001]) and advanced age (≥70 years, 1.13%; <70 years, 1.02% [P < .001]).

Conclusions

Many patients with T2DM have very high HbA1c levels when initiating second‐line therapy, indicating the need for earlier treatment intensification. Patient‐specific factors merit consideration when making treatment decisions.
Effect of once‐weekly dulaglutide on glycated haemoglobin (HbA1c) and fasting blood glucose in patient subpopulations by gender, duration of diabetes and baseline HbA1c
Authors: Gallwitz Baptist , Dagogo‐Jack Samuel , Thieu Vivian , Garcia‐Perez Luis‐Emilio , Pavo Imre , Yu Maria , Robertson Kenneth E. , Zhang Nan , Giorgino Francesco
Published: August 2017

Aims

To evaluate the efficacy and safety of dulaglutide 1.5 and 0.75 mg in patients with type 2 diabetes by subgroups of gender, duration of diabetes and baseline glycated haemoglobin (HbA1c) in the dulaglutide clinical development programme (AWARD‐1 to ‐6 and ‐8 clinical trials).

Methods

Change in HbA1c was analysed by gender, duration of diabetes (<5, ≥5 years and <10, ≥10 years), and baseline HbA1c (<8.5%, ≥8.5%) in pooled and individual studies. Changes from baseline in weight, hypoglycaemia and gastrointestinal adverse events were evaluated for individual trials.

Results

In the pooled analysis of patients treated with dulaglutide 1.5 mg at 6 months, the reductions in HbA1c from baseline were similar across gender (men: least squares [LS] mean −1.26% [95% confidence interval {CI} −1.36, −1.16]; women: LS mean −1.33% [95% CI −1.43, −1.24]) and among duration of diabetes subgroups (<5 years: LS mean −1.32% [95% CI −1.43, −1.22]; ≥5 and <10 years: LS mean −1.33% [95% CI −1.43, −1.22]; ≥10 years: −1.24% [95% CI −1.35, −1.14]). Patients with baseline HbA1c ≥8.5% had greater HbA1c reductions than patients with baseline HbA1c <8.5%, (≥8.5%: LS mean −1.86% [95% CI −1.97, −1.75]; <8.5%: LS mean −1.02% [95% CI −1.12, −0.93]). Reductions in fasting blood glucose (FBG) were consistent with HbA1c changes. Similar results were observed with dulaglutide 0.75 mg. In general, body weight changes were similar among duration of diabetes and in baseline HbA1c subgroups, respectively; women had a numerically greater weight loss or less weight gain than men with both dulaglutide doses. There was no clinically meaningful difference in hypoglycaemia trends by gender or duration of diabetes. Hypoglycaemia incidence and rate were generally lower in patients with baseline HbA1c ≥8.5% than in those with <8.5%, except for the AWARD‐4 study (combination with mealtime insulin).

Conclusions

Across the AWARD studies, dulaglutide demonstrated significant improvements in glycaemic control irrespective of gender, duration of diabetes, or baseline HbA1c, with greater HbA1c and FBG reductions in patients with a higher baseline HbA1c. Dulaglutide was well tolerated, with a safety profile similar to other glucagon‐like peptide‐1 receptor agonists.
Attenuated suppression of lipolysis explains the increases in triglyceride secretion and concentration associated with basal insulin peglispro relative to insulin glargine treatment in patients with type 1 diabetes
Authors: Johansen Rakel F. , Søndergaard Esben , Linnebjerg Helle , Garhyan Parag , Lam Eric C. Q. , Porksen Niels , Jacober Scott J. , Nielsen Søren
Published: August 2017

Aims

To test the hypothesis that, as well as lowering weight and increasing plasma triglyceride (TG) levels and hepatic fat compared with insulin glargine (GL) in patients with type 1 diabetes, the attenuated peripheral effects of basal insulin peglispro (BIL) may include increased free fatty acid flux to the liver, causing increased very‐low‐density lipoprotein (VLDL)‐TG secretion and lipid oxidation, and decreased TG adipose tissue deposition.

Methods

In this open‐label, randomized, 2‐period crossover study, 14 patients with type 1 diabetes received once‐daily, individualized, stable BIL or GL doses for 3 weeks. Palmitate flux was assessed using [9,10‐3H]palmitate infusion. VLDL‐TG secretion, clearance and oxidation rate were assessed using primed‐constant infusion of ex vivo labelled [1‐14C]VLDL‐TG, while VLDL‐TG storage rate was assessed using [9,10‐3H]VLDL‐TG bolus injection.

Results

The VLDL‐TG concentration and secretion rate, and palmitate flux were statistically significantly higher during BIL than during GL treatment (58%, 51% and 35%, respectively). The ratios of least squares (LS) geometric means for VLDL‐TG clearance and oxidation were 0.92 (95% confidence interval [CI] 0.72, 1.17) and 1.31 (95% CI 0.91, 1.90), respectively. The difference in LS means for VLDL‐TG storage rate was −0.36 (95% CI −0.83, 0.12).

Conclusions

BIL‐treated patients had higher effective lipolysis, VLDL‐TG secretion and VLDL‐TG concentration compared with GL‐treated patients, explaining the increased plasma TG concentrations reported previously. Data support attenuated effects of BIL on lipolysis, in addition to the recently described hepato‐preferential glucodynamic effects.
Plasma and cerebrospinal fluid tau and neurofilament concentrations in rapidly progressive neurological syndromes: a neuropathology‐based cohort
Authors: Kovacs G. G. , Andreasson U. , Liman V. , Regelsberger G. , Lutz M. I. , Danics K. , Keller E. , Zetterberg H. , Blennow K.
Published: August 2017

Background and purpose

Cerebrospinal fluid (CSF) tau and neurofilament light chain (NF‐L) proteins have proved to be reliable biomarkers for neuronal damage; however, there is a strong need for blood‐based tests.

Methods

The present study included 132 autopsy cases with rapidly progressive neurological syndromes, including Alzheimer disease (AD) (21), sporadic (65) and genetic (21) Creutzfeldt–Jakob disease (CJD), 25 cases with vascular, neoplastic and inflammatory alterations, and additionally 18 healthy control individuals. CSF tau and NF‐L concentrations were measured by enzyme‐linked immunosorbent assay. Plasma tau and NF‐L concentrations were measured using ultra‐sensitive single molecule array technology.

Results

Plasma and CSF tau (R = 0.59, P < 0.001) and NF‐L (R = 0.69, P < 0.001) levels correlated significantly (Spearman test). Plasma tau and NF‐L levels were significantly higher in all disease groups compared to healthy controls (P < 0.001). Receiver operating characteristic curves were used and area under the curve values for comparisons with controls were 0.82 (AD), 0.94 (sporadic CJD), 0.92 (genetic CJD) and 0.83 (other neurological disorders) for plasma tau and 0.99, 0.99, 1.00 and 0.96 for plasma NF‐L, respectively. Molecular subtyping of sporadic CJD showed a strong effect (linear logistic regression) on plasma tau (P < 0.001) but not NF‐L levels (P = 0.19).

Conclusion

Plasma tau and NF‐L concentrations are strongly increased in CJD and show similar diagnostic performance to the corresponding CSF measure. Molecular subtypes of sporadic CJD show different levels of plasma tau. Although not disease‐specific, these findings support the use of plasma tau and NF‐L as tools to identify, or to rule out, neurodegeneration.
Huntington's disease: a clinical review
Authors: McColgan P. , Tabrizi S. J.
Published: August 2017

Huntington's disease (HD) is a fully penetrant neurodegenerative disease caused by a dominantly inheritedCAGtrinucleotide repeat expansion in the huntingtin gene on chromosome 4. In Western populationsHDhas a prevalence of 10.6–13.7 individuals per 100 000. It is characterized by cognitive, motor and psychiatric disturbance. At the cellular level mutant huntingtin results in neuronal dysfunction and death through a number of mechanisms, including disruption of proteostasis, transcription and mitochondrial function and direct toxicity of the mutant protein. Early macroscopic changes are seen in the striatum with involvement of the cortex as the disease progresses. There are currently no disease modifying treatments; therefore supportive and symptomatic management is the mainstay of treatment. In recent years there have been significant advances in understanding both the cellular pathology and the macroscopic structural brain changes that occur as the disease progresses. In the last decade there has been a large growth in potential therapeutic targets and clinical trials. Perhaps the most promising of these are the emerging therapies aimed at lowering levels of mutant huntingtin. Antisense oligonucleotide therapy is one such approach with clinical trials currently under way. This may bring us one step closer to treating and potentially preventing this devastating condition.
Thelytokous parthenogenesis in the exotic dacetine ant Strumigenys rogeri (Hymenoptera: Formicidae) in Taiwan
Authors: Lee Ching‐Chen , Hsu Shu‐Fen , Yang Chin‐Cheng (Scotty) , Lin Chung‐Chi
Published: August 2017

Only recently has it become clear that several species of eusocial hymenopterans regularly reproduce by thelytokous parthenogenesis, that is, the production of diploid female offspring by unmated females. This phenomenon suggests that parthenogenetic reproduction might be advantageous to organisms under certain environmental conditions. Here the occurrence of asexual reproduction is reported for the first time in the dacetine ant, Strumigenys rogeri, at least for the focal populations in Taiwan. Virgin queens of S. rogeri maintained with several workers produced both workers and young queens from unfertilized eggs under laboratory conditions in as short as 39 days, whereas workers were strictly sterile as no spermatheca was discovered after dissection. Combined with additional evidence (i.e. absence of males in field colonies), queen thelytoky is confirmed. Such a reproductive mode and short development time may jointly help explain the success of this tramp ant species in Taiwan and elsewhere.
Competing Supremacies and Clashing Institutional Rationalities: the Danish Supreme Court's Decision in the Ajos Case and the National Limits of Judicial Cooperation
Authors: Madsen Mikael Rask , Olsen Henrik Palmer , Šadl Urška
Published: August 2017

On 6 December 2016, the Supreme Court of Denmark (SCDK) ruled on the grounds of Ajos case. The ruling concerned the scope of the principle of non‐discrimination on the grounds of age and whether a national court could weigh the principle of non‐discrimination on grounds of age against the principles of legal controversy, as the protection of legitimate expectations. The ruling has caused a great deal of controversy as the SCDK defied clear guidelines from the Court of Justice of the European Union (CJEU) in the ruling. Moreover, the case has been seen by some as an example of a new ‘sovereigntism’ in Danish law that is at odds with the project of European integration through law. This article explains the case from both an EU law and Danish constitutional law perspective. It concludes by providing a set of explanations of the new course of the SCDK in its relationship with the EU.
Going Unnoticed? Diagnosing the Right to Asylum in the Charter of Fundamental Rights of the European Union
Authors: Nicolosi Salvatore Fabio
Published: August 2017

Article 18 of the Charter of Fundamental Rights of the European Union enshrines the right to asylum. Nonetheless, despite its ‘constitutionalisation’ within primary law, asylum remains a far too amorphous right, whose axiological potential has gone virtually unnoticed in the ongoing migratory crisis. The paper will argue that this is partly due to the fact that the Court of Justice on a few occasions has declined to clarify the scope of Article 18. The provision at issue therefore remains a pathological element that requires an adequate diagnosis on which accurate prognoses can be based. In an attempt to diagnose the right to asylum enshrined in Article 18 of the Charter of Fundamental Rights of the EU, this paper will compare different hermeneutical approaches and reflect on the contextualisation of the mentioned provision through the lens of domestic and EU case law and in the light of the recent EU–Turkey Statement. The article will ultimately propose to interpret the EU asylum legislation as instrumental to the effective exercise of the right to asylum.
An approach based on risk to dimensioning virtual organizations
Authors: Ferreira Jonathan Emannoel , Fiorese Adriano
Published: August 2017

In an increasingly competitive market, small and medium enterprises have the temporarily option to divide their core competencies in sub‐competences. In fact, this is the purpose of so‐called virtual organizations (VOs), which aim to attend a particular goal joining partner forces. However, when these VOs are created, it is necessary to deal with the maximum number of participants involved in the process and the risk involved in these relationships, which should be measured through a well‐defined process. This paper aims to present an approach to dimensioning the maximum number of participants involved in the formation of a VO composed of several service providers. This approach is based on the overall risk level of the participants and uses different risk analysis methods to assess the suitable number of participants to be part of a VO.
Deciding to Come Out to Parents: Toward a Model of Sexual Orientation Disclosure Decisions
Authors: Grafsky Erika L.
Published: August 2017

The purpose of this study was to conduct research to understand nonheterosexual youths’ decision to disclose their sexual orientation information to their parents. The sample for this study includes 22 youth between the ages of 14 and 21. Constructivist grounded theory guided the qualitative methodology and data analysis. The findings from this study posit an emerging model of sexual orientation disclosure decisions comprised of four interrelated factors that influence the decision to disclose or not disclose, as well as a description of the mechanism through which disclosure either does or does not occur. Clinical implications and recommendations for further research are provided.
T3SS effector ExoY reduces inflammasome‐related responses by suppressing bacterial motility and delaying activation of NF‐κB and caspase‐1
Authors: Jeon Jisu , Kim Yong‐Jae , Shin Heesung , Ha Un‐Hwan
Published: August 2017

Type III‐secreted effectors are essential for modulating host immune responses during the pathogenesis of Pseudomonas aeruginosa infections. Little is known about the impact of one of the effectors, ExoY, on inflammasome activation, which results in IL‐1β production and pyroptotic cell death. In this study, we found that transcriptional expression of Il‐1β was induced to a lesser extent in response to an exoY‐harboring strain than to a deleted mutant. This suppressive effect of ExoY was verified by complementation assay as well as by direct translocation of exoY into host cells. In addition to the production of IL‐1β, pyroptotic cell death was also diminished in response to an exoY‐harboring strain. These inflammasome responses were mediated by the adenylate cyclase activity of ExoY, which plays a role in delaying the activation of NF‐κB and caspase‐1, a key component of inflammasome‐mediated responses. Moreover, the negative effects of ExoY on these responses were in part conferred by the suppression of bacterial motility, which could reduce the degree of bacterial contact with cells. Together, these results demonstrate that the adenylate cyclase activity of P. aeruginosa ExoY can reduce inflammasome‐related responses by influencing both the host and the bacterium itself by delaying the activation of inflammatory pathways and suppressing bacterial motility.
Some influencing variables on internal fatigue crack initiation in structural materials
Authors: Ebara R.
Published: August 2017

This paper emphasizes the important effect of Kt and corrosive environment on internal fatigue crack initiation of structural materials in very high cycle regime. The conventional and ultrasonic fatigue testing results on notched specimens with Kt of 1.5 to 2.5 for YXR3 steel with HRC 60.7 showed subsurface fatigue crack initiation on all notched specimens at Nf higher than 106. On the contrary, fatigue crack initiated at notched surface for HAP72 with HRC 67 with Kt of 2.0. The fatigue crack initiation mode in notched specimens at high cycle regime is governed by surface hardness of high strength steels. The contrasting effect of refrigeration compressor gaseous environment on fatigue crack initiation mode is also demonstrated in the plate bending fatigue testing results of 1% carbon steel.
The spatial distribution of soil organic carbon in tidal wetland soils of the continental United States
Authors: Hinson Audra L. , Feagin Rusty A. , Eriksson Marian , Najjar Raymond G. , Herrmann Maria , Bianchi Thomas S. , Kemp Michael , Hutchings Jack A. , Crooks Steve , Boutton Thomas
Published: August 2017

Tidal wetlands contain large reservoirs of carbon in their soils and can sequester carbon dioxide (CO2) at a greater rate per unit area than nearly any other ecosystem. The spatial distribution of this carbon influences climate and wetland policy. To assist with international accords such as the Paris Climate Agreement, national‐level assessments such as the United States (U.S.) National Greenhouse Gas Inventory, and regional, state, local, and project‐level evaluation of CO2 sequestration credits, we developed a geodatabase (CoBluCarb) and high‐resolution maps of soil organic carbon (SOC) distribution by linking National Wetlands Inventory data with the U.S. Soil Survey Geographic Database. For over 600,000 wetlands, the total carbon stock and organic carbon density was calculated at 5‐cm vertical resolution from 0 to 300 cm of depth. Across the continental United States, there are 1,153–1,359 Tg of SOC in the upper 0–100 cm of soils across a total of 24 945.9 km2 of tidal wetland area, twice as much carbon as the most recent national estimate. Approximately 75% of this carbon was found in estuarine emergent wetlands with freshwater tidal wetlands holding about 19%. The greatest pool of SOC was found within the Atchafalaya/Vermilion Bay complex in Louisiana, containing about 10% of the U.S. total. The average density across all tidal wetlands was 0.071 g cm−3 across 0–15 cm, 0.055 g cm−3 across 0–100 cm, and 0.040 g cm−3 at the 100 cm depth. There is inherent variability between and within individual wetlands; however, we conclude that it is possible to use standardized values at a range of 0–100 cm of the soil profile, to provide first‐order quantification and to evaluate future changes in carbon stocks in response to environmental perturbations. This Tier 2‐oriented carbon stock assessment provides a scientific method that can be copied by other nations in support of international requirements.
Immunogenicity, efficacy and safety of Nuwiq® (human‐cl rhFVIII) in previously untreated patients with severe haemophilia A—Interim results from the NuProtect Study
Authors: Liesner R. J. , Abashidze M. , Aleinikova O. , Altisent C. , Belletrutti M. J. , Borel‐Derlon A. , Carcao M. , Chambost H. , Chan A. K. C. , Dubey L. , Ducore J. , Fouzia N. A. , Gattens M. , Gruel Y. , Guillet B. , Kavardakova N. , El Khorassani M. , Klukowska A. , Lambert T. , Lohade S. , Sigaud M. , Turea V. , Wu J. K. M. , Vdovin V. , Pavlova A. , Jansen M. , Belyanskaya L. , Walter O. , Knaub S. , Neufeld E. J.
Published: August 2017

Introduction

Nuwiq® (Human‐cl rhFVIII) is a fourth generation recombinant FVIII, produced in a human cell line, without chemical modification or protein fusion. No inhibitors developed in studies with Nuwiq® in 201 previously treated patients with haemophilia A (HA). The immunogenicity, efficacy and safety of Nuwiq® in previously untreated patients (PUPs) with severe HA are being assessed in the ongoing NuProtect study.

Methods

The study, conducted across 38 centres worldwide, is evaluating 110 true PUPs of all ages and ethnicities enrolled for study up to 100 exposure days (EDs) or 5 years maximum. The primary objective is to assess the immunogenicity of Nuwiq® (inhibitor activity ≥0.6 BU) using the Nijmegen‐modified Bethesda assay at a central laboratory.

Results

Data for 66 PUPs with ≥20 EDs from a preplanned interim analysis were analysed. High‐titre (HT) inhibitors developed in 8 of 66 patients after a median of 11.5 EDs (range 6‐24). Five patients developed low‐titre inhibitors (4 transient). The cumulative incidence (95% confidence interval) was 12.8% (4.5%, 21.2%) for HT inhibitors and 20.8% (10.7%, 31.0%) for all inhibitors. During inhibitor‐free periods, median annualized bleeding rates during prophylaxis were 0 for spontaneous bleeds and 2.40 for all bleeds. Efficacy was rated as “excellent” or “good” in treating 91.8% of bleeds. Efficacy of surgical prophylaxis was “excellent” or “good” for 8 (89%) procedures and “moderate” for 1 (11%). No tolerability concerns were evident.

Conclusion

These interim data show a cumulative incidence of 12.8% for HT inhibitors and convincing efficacy and tolerability in PUPs treated with Nuwiq®.
Application of the condensed protocol for the NIA‐AA guidelines for the neuropathological assessment of Alzheimer's disease in an academic clinical practice
Authors: Bharadwaj Rajnish , Cimino Patrick J , Flanagan Margaret E , Latimer Caitlin S , Gonzalez‐Cuyar Luis F , Juric‐Sekhar Gordana , Montine Thomas J , Marshall Desiree A , Keene C. Dirk
Published: August 2017

Aims

In response to concerns regarding resource expenditures required to implement fully the 2012 National Institute on Aging and the Alzheimer's Association (NIA‐AA) Sponsored Guidelines for the neuropathological assessment of Alzheimer's disease (AD), we previously developed a sensitive and cost‐reducing condensed protocol (CP) at the University of Washington (UW) Alzheimer's Disease Research Center (ADRC) that consolidated the recommended NIA‐AA protocol into fewer cassettes requiring fewer immunohistochemical stains. The CP was not designed to replace NIA‐AA protocols, but instead to make the NIA‐AA criteria accessible to clinical and forensic neuropathology practices where resources limit full implementation of NIA‐AA guidelines.

Methods and results

In this regard, we developed practical criteria to instigate CP sampling and immunostaining, and applied these criteria in an academic clinical neuropathological practice. During the course of 1 year, 73 cases were sampled using the CP; of those, 53 (72.6%) contained histological features that prompted CP work‐up. We found that the CP resulted in increased identification of AD and Lewy body disease neuropathological changes from what was expected using a clinical history‐driven work‐up alone, while saving approximately $900 per case.

Conclusions

This study demonstrates the feasibility and cost‐savings of the CP applied to a clinical autopsy practice, and highlights potentially unrecognised neurodegenerative disease processes in the general ageing community.
HIV‐infected patients' beliefs about their chronic co‐treatments in comparison with their combined antiretroviral therapy
Authors: Kamal S , Bugnon O , Cavassini M , Schneider MP
Published: August 2017

Objectives

Thanks to the success of combination antiretroviral therapy (cART), HIV‐infected patients can have almost a normal life expectancy. This has resulted in an aging HIV‐infected population with other chronic comorbidities such as cardiovascular diseases, osteoporosis, and depression. Our hypothesis is that patients' perceptions of and attitudes towards their cART, which is perceived as crucial to their survival, differ from their beliefs about their co‐treatments, and this may have an impact on their medication adherence.

Methods

We used the French version of the Beliefs about Medicine Questionnaire (BMQ‐f) to measure the perceptions of patients about their co‐treatments and the Beliefs about Medicine Questionnaire for Highly Active Antiretroviral Therapy (BMQ‐HAART) to measure their beliefs about their cART in a representative sample (n = 150) of patients enrolled in the Swiss HIV Cohort Study (SHCS) and followed at the Infectious Disease Service at the University Hospital in Lausanne, Switzerland. The survey was administered to all eligible patients by the order of their scheduled appointments at the end of their medical visit. The BMQ comprises two subscores: Specific‐Necessity (5 identical items in BMQ‐f and BMQ‐HAART) and Specific‐Concerns (also 5 identical items in BMQ‐f and BMQ‐HAART). The subscores were standardized by dividing the score scale by the number of questions in the scale, resulting in a range of responses between 1 (low) and 5 (high). Self‐reported medication adherence was measured using the SHCS Adherence Questionnaire (SHCS‐AQ). Adherence was defined as not missing any dose or missing one dose of the treatment in the past 4 weeks. Sociodemographic variables were retrieved by reviewing the SHCS database.

Results

A response rate of 73% (109 of 150) was achieved. A total of 105 patients were included in the analysis: their median age was 56 [interquartile range (IQR) 51, 63] years and 74 were male (70%). Eighty‐seven patients (83%) were adherent to cART and 75 (71%) were adherent to their co‐treatments (P = 0.0001). The standardized mean responses for the BMQ Specific‐Necessity subscores were 4.46 [standard deviation (SD): 0.58] and 2.86 (SD: 1.02) for cART and co‐treatments, respectively (P < 0.0001). For Specific‐Concerns, the standardized mean responses were 2.9 (SD: 1.02) for cART and 4.09 (SD: 1.02) (P < 0.0001) for co‐treatments. cART and co‐treatment concerns increased as the number of co‐treatments increased (P = 0.03 and P < 0.0001, respectively).

Conclusions

Patients had higher Necessity and lower Concerns scores for their cART in comparison with their co‐treatments. A higher percentage of patients reported being adherent to cART compared with the co‐treatments that they reported they were most likely to miss. Further research using a bigger sample size and more objective measures of adherence is needed to explore the association between adherence and patients' perceptions.
Pathophysiology of nocturnal lower urinary tract symptoms in older patients with urinary incontinence
Authors: Denys Marie‐Astrid , Decalf Veerle , Kumps Candy , Petrovic Mirko , Goessaert An‐Sofie , Everaert Karel
Published: August 2017

Objectives

To explore the mismatch between functional bladder capacity and nocturnal urine production, and to study the pathophysiology of an increased nocturnal urine production in older patients with urinary incontinence.

Methods

The present prospective observational study included adults aged ≥65 years with urinary incontinence. Participants completed questionnaires, frequency volume charts and renal function profiles. The nocturnal lower urinary tract symptom index was defined as nocturnal urine output/maximum voided volume; the nocturnal polyuria index as nocturnal/24 h urine output.

Results

The median age (n = 95) was 74 years (69–79), 87% were women and 73% had nocturnal lower urinary tract symptoms (nocturnal urinary incontinence or nocturia ≥2). Participants with nocturnal lower urinary tract symptoms had a significantly higher nocturnal urine output (809 mL vs 650 mL; P = 0.001) and no significant difference in maximum voided volume (350 mL vs 437 mL; P = 0.079) compared with participants without nocturnal lower urinary tract symptoms. Participants (nocturnal polyuria index >33% [n = 56], nocturnal polyuria index >40% [n = 42], nocturnal lower urinary tract symptom index >1.87 [n = 51]) showed higher night‐time diuresis rates, free water and sodium clearance compared with during the daytime. Controls (nocturnal polyuria index ≤33% [n = 26], nocturnal polyuria index ≤40% [n = 40], nocturnal lower urinary tract symptom index ≤1.87 [n = 44]) had no circadian rhythm in their diuresis rate or sodium clearance, but more nocturnal free water clearance compared with during the daytime.

Conclusions

The majority of older adults with urinary incontinence present nocturnal lower urinary tract symptoms. An increased nocturnal sodium diuresis seems to be the only mechanism differentiating patients with nocturnal lower urinary tract symptoms from controls.
T helper type 1 polarizing γδ T cells and Scavenger receptors contribute to the pathogenesis of Pemphigus vulgaris
Authors: Das Dayasagar , Anand Vivek , Khandpur Sujay , Sharma Vinod K. , Sharma Alpana
Published: August 2017

γδ T cells and Scavenger receptors are key parts of the innate immune machinery, playing significant roles in regulating immune homeostasis at the epithelial surface. The roles of these immune components are not yet characterized for the autoimmune skin disorder Pemphigus vulgaris (PV). Phenotyping and frequency of γδ T cells estimated by flow cytometry have shown increased frequency of γδ T cells (6·7% versus 4·4%) producing interferon‐ γ (IFN‐γ; 35·2% versus 26·68%) in the circulation of patients compared with controls. Dual cytokine‐secreting (IFN‐γ and interleukin‐4) γδ T cells indicate the plasticity of these cells. The γδ T cells of patients with PV have shown higher cytotoxic potential and the higher frequency of γδ T cells producing IFN‐γ shows T helper type 1 polarization. The increased expression of Scavenger receptors expression (CD36 and CD163) could be contributing to the elevated inflammatory environment and immune imbalance in this disease. Targeting the inflammatory γδ T cells and Scavenger receptors may pave the way for novel therapeutics.
What Does Objective Mean in a Dirichlet‐multinomial Process?
Authors: Alvares Danilo , Armero Carmen , Forte Anabel
Published: August 2017

The Dirichlet‐multinomial process can be seen as the generalisation of the binomial model with beta prior distribution when the number of categories is larger than two. In such a scenario, setting informative prior distributions when the number of categories is great becomes difficult, so the need for an objective approach arises. However, what does objective mean in the Dirichlet‐multinomial process? To deal with this question, we study the sensitivity of the posterior distribution to the choice of an objective Dirichlet prior from those presented in the available literature. We illustrate the impact of the selection of the prior distribution in several scenarios and discuss the most sensible ones.
Supporting end of life decision making: Case studies of relational closeness in supported decision making for people with severe or profound intellectual disability
Authors: Watson Joanne , Wilson Erin , Hagiliassis Nick
Published: August 2017

Background

The United Nations Convention on the Rights of Persons with Disabilities (UNCRPD) promotes the use of supported decision making in lieu of substitute decision making. To date, there has been a lack of focus on supported decision making for people with severe or profound intellectual disability, including for end of life decisions.

Methods

Five people with severe or profound intellectual disability's experiences of supported decision making were examined. This article is particularly focused on one participant's experiences at the end of his life.

Results

All five case studies identified that supporters were most effective in providing decision‐making support for participants when they were relationally close to the person and had knowledge of the person's life story, particularly in relation to events that demonstrated preference.

Conclusions

Findings from this study provide new understandings of supported decision making for people with severe or profound intellectual disability and have particular relevance for supporting decision making at the end of life.
Biogeography and temporal progression during the evolution of striped dolphin population structure in European waters
Authors: Gkafas Georgios A. , Exadactylos Athanassios , Rogan Emer , Raga Juan Antonio , Reid Robert , Hoelzel A. Rus
Published: August 2017

Aim

We investigated the population genetic structure of a highly mobile marine species, the striped dolphin, Stenella coeruleoalba (Meyen, 1833), along a geographical range with habitat transitions and historical dynamics to identify the causes of genetic divergence, and to assess the effect of past climate change on demography and population connectivity.

Location

North‐east Atlantic Ocean and Mediterranean Sea.

Methods

Twenty microsatellite loci were used in conjunction with coalescent methods to investigate the genetic structure and demographic history of striped dolphins (Stenella coeruleoalba) in the Mediterranean Sea and eastern North Atlantic Ocean. Approximate Bayesian modelling was used to compare the support for alternative scenarios for the pattern of divergence over time in the context of known geographical transitions and environmental change over the course of the Quaternary.

Results

We describe a novel pattern of structure among the extant populations along north–south and east–west axes. Modern gene flow shows strong directionality from north‐east to south and west in the North Atlantic, and from west to east in the Mediterranean. On a temporal scale we found evidence for a progression starting with a division between the North Atlantic and Mediterranean Sea populations during the middle Pleistocene, followed by a division within the Mediterranean between the east and west basins towards the end of the Pleistocene, and finally an east–west division in the eastern North Atlantic at the start of the Holocene.

Main conclusions

In the context of known population structure for other marine species along the same geographical range, our data facilitate inference of the more general processes that shaped patterns of biogeography across this region through the environmental transitions of the Quaternary. In particular, Pleistocene era divisions apparently reflect strong physical habitat boundaries, with later divisions associated with climate warming in the Holocene.
CD38 deficiency suppresses adipogenesis and lipogenesis in adipose tissues through activating Sirt1/PPARγ signaling pathway
Authors: Wang Ling‐Fang , Miao Lian‐Jie , Wang Xiao‐Nv , Huang Cong‐Cong , Qian Yi‐Song , Huang Xuan , Wang Xiao‐Lei , Jin Wan‐Zhu , Ji Guang‐Ju , Fu Mingui , Deng Ke‐Yu , Xin Hong‐Bo
Published: August 2017

It has been recently reported that CD38 was highly expressed in adipose tissues from obese people and CD38‐deficient mice were resistant to high‐fat diet (HFD)‐induced obesity. However, the role of CD38 in the regulation of adipogenesis and lipogenesis is unknown. In this study, to explore the roles of CD38 in adipogenesis and lipogenesis in vivo and in vitro, obesity models were generated with male CD38−/− and WT mice fed with HFD. The adipocyte differentiations were induced with MEFs from WT and CD38−/− mice, 3T3‐L1 and C3H10T1/2 cells in vitro. The lipid accumulations and the alternations of CD38 and the genes involved in adipogenesis and lipogenesis were determined with the adipose tissues from the HFD‐fed mice or the MEFs, 3T3‐L1 and C3H10T1/2 cells during induction of adipocyte differentiation. The results showed that CD38−/− male mice were significantly resistant to HFD‐induced obesity. CD38 expressions in adipocytes were significantly increased in WT mice fed with HFD, and the similar results were obtained from WT MEFs, 3T3‐L1 and C3H10T1/2 during induction of adipocyte differentiation. The expressions of PPARγ, AP2 and C/EBPα were markedly attenuated in adipocytes from HFD‐fed CD38−/− mice and CD38−/− MEFs at late stage of adipocyte differentiation. Moreover, the expressions of SREBP1 and FASN were also significantly decreased in CD38−/− MEFs. Finally, the CD38 deficiency‐mediated activations of Sirt1 signalling were up‐regulated or down‐regulated by resveratrol and nicotinamide, respectively. These results suggest that CD38 deficiency impairs adipogenesis and lipogenesis through activating Sirt1/PPARγ‐FASN signalling pathway during the development of obesity.
Lactuca capensis reverses memory deficits in Aβ1‐42‐induced an animal model of Alzheimer's disease
Authors: Postu Paula Alexandra , Noumedem Jaures A. K. , Cioanca Oana , Hancianu Monica , Mihasan Marius , Ciorpac Mitica , Gorgan Dragos Lucian , Petre Brindusa Alina , Hritcu Lucian
Published: August 2017

We investigated the neuropharmacological effects of the methanolic extract from Lactuca capensis Thunb. leaves (100 and 200 mg/kg) for 21 days on memory impairment in an Alzheimer's disease (AD) rat model produced by direct intraventricular delivery of amyloid‐β1‐42 (Aβ1‐42). Behavioural assays such as Y‐maze and radial arm maze test were used for assessing memory performance. Aβ1‐42 decreased cognitive performance in the behavioural tests which were ameliorated by pre‐treatment with the methanolic extract. Acetylcholinesterase activity and oxidant–antioxidant balance in the rat hippocampus were abnormally altered by Aβ1‐42 treatment while these deficits were recovered by pre‐treatment with the methanolic extract. In addition, rats were given Aβ1‐42 exhibited in the hippocampus decreased brain‐derived neurotrophic factor (BDNF) mRNA copy number and increased IL‐1β mRNA copy number which was reversed by the methanolic extract administration. These findings suggest that the methanolic extract could be a potent neuropharmacological agent against dementia via modulating cholinergic activity, increasing of BDNF levels and promoting antioxidant action in the rat hippocampus.
Bateman purpura (dermatoporosis): a localized scurvy treated by topical vitamin C – double‐blind randomized placebo‐controlled clinical trial
Authors: Humbert P. , Fanian F. , Lihoreau T. , Jeudy A. , Pierard G.E.
Published: August 2017

Background

Bateman purpura is characterized by diffuse senile skin atrophy, senile purpura and spontaneous stellar pseudocicatrices. Cutaneous changes in the course of ageing have been related to lower levels of ascorbic acid into the dermis of elderly people.

Objective

In this study, we postulate that senile purpura could be linked to dermal vitamin C deficiency and could be corrected by topical administration of this vitamin.

Methods

A 12‐weeks, hemi‐member (forearm or leg), randomized double‐blind comparative study was conducted in 18 patients with Bateman purpura aged over than 60 years. At each visit, clinical assessment and biometrological measurements were performed. Clinical examination and scoring by experts showed a significant improvement on the vitamin C‐treated side compared with the control, with reduction of haemorrhage areas, increase of dermal thickness.

Results

Twice‐daily application of 5% topical vitamin C led to a clinically apparent improvement of the skin symptoms and allows beneficial effects on skin elasticity and thickness. Bateman purpura, a classical sign of photoaging whose origin has not clearly been recognized could be improved by vitamin C applied on to the skin.

Conclusion

These results confirm the hypothesis of the underlying role of vitamin C deficiency in the determinism of Bateman purpura.
The tooth, the whole tooth and nothing but the tooth: tooth shape and ontogenetic shift dynamics in the white sharkCarcharodon carcharias
Authors: French G. C. A. , Stürup M. , Rizzuto S. , van Wyk J. H. , Edwards D. , Dolan R. W. , Wintner S. P. , Towner A. V. , Hughes W. O. H.
Published: August 2017

Results from this study of the white sharkCarcharodon carchariasinclude measurements obtained using a novel photographic method that reveal significant differences between the sexes in the relationship between tooth cuspidity and shark total length, and a novel ontogenetic change in male tooth shape. Males exhibit broader upper first teeth and increased distal inclination of upper third teeth with increasing length, while females do not present a consistent morphological change. Substantial individual variation, with implications for pace of life syndrome, was present in males and tooth polymorphism was suggested in females. Sexual differences and individual variation may play major roles in ontogenetic changes in tooth morphology inC. carcharias, with potential implications for their foraging biology. Such individual and sexual differences should be included in studies of ontogenetic shift dynamics in other species and systems.
Usefulness of shear wave elastography as a quantitative diagnosis of chronic pancreatitis
Authors: Kuwahara Takamichi , Hirooka Yoshiki , Kawashima Hiroki , Ohno Eizaburo , Ishikawa Takuya , Yamamura Takeshi , Furukawa Kazuhiro , Funasaka Kohei , Nakamura Masanao , Miyahara Ryoji , Watanabe Osamu , Ishigami Masatoshi , Hashimoto Senju , Goto Hidemi
Published: August 2017

Background and Aim

Chronic pancreatitis (CP) is sometimes diagnosed at the progressed stage. For the early diagnosis of CP, endoscopic ultrasonography (EUS) may be a useful method, but its diagnostic criteria is based on subjective judgment. Shear wave elastography (SW‐EG) using transabdominal ultrasonography, which quantifies tissue elasticity as an absolute value, may be an objective and noninvasive method for the diagnosis of CP.

Methods

Eighty‐five patients with known or suspected CP who underwent both EUS and SW‐EG from October 2012 to July 2016 were included in this study. Patients were categorized into four stages using Rosemont classification and into three stages using Japan Pancreas Society clinical diagnostic criteria 2009 that was EUS‐based criteria for the diagnosis of CP. SW‐EG was measured five times in the pancreatic parenchyma, and the median value was defined as the pancreatic elastic modulus (PEM).

Results

Pancreatic elastic modulus was significantly positively correlated with Rosemont classification stage (rs = 0.54), Japan Pancreas Society stage (rs = 0.41), and the number of EUS features (rs = 0.47). Area under the receiver operating characteristic curve for the accuracy of SW‐EG (consistent with CP and suggestive of CP vs normal and indeterminate for CP) was 0.77 (sensitivity 77.1%, specificity 64.9%). In a multivariate linear regression analysis including various EUS features related to PEM, hyperechoic foci with shadowing and lobularity with honeycombing were independent features related to PEM.

Conclusions

Chronic pancreatitis may be diagnosed noninvasively and objectively using SW‐EG without performing EUS.
Registration of phase‐contrast images in propagation‐based X‐ray phase tomography
Authors: WEBER L. , HÄNSCH A. , WOLFRAM U. , PACUREANU A. , CLOETENS P. , PEYRIN F. , RIT S. , LANGER M.
Published: August 2017

X‐ray phase tomography aims at reconstructing the 3D electron density distribution of an object. It offers enhanced sensitivity compared to attenuation‐based X‐ray absorption tomography. In propagation‐based methods, phase contrast is achieved by letting the beam propagate after interaction with the object. The phase shift is then retrieved at each projection angle, and subsequently used in tomographic reconstruction to obtain the refractive index decrement distribution, which is proportional to the electron density. Accurate phase retrieval is achieved by combining images at different propagation distances. For reconstructions of good quality, the phase‐contrast images recorded at different distances need to be accurately aligned. In this work, we characterise the artefacts related to misalignment of the phase‐contrast images, and investigate the use of different registration algorithms for aligning in‐line phase‐contrast images. The characterisation of artefacts is done by a simulation study and comparison with experimental data. Loss in resolution due to vibrations is found to be comparable to attenuation‐based computed tomography. Further, it is shown that registration of phase‐contrast images is nontrivial due to the difference in contrast between the different images, and the often periodical artefacts present in the phase‐contrast images if multilayer X‐ray optics are used. To address this, we compared two registration algorithms for aligning phase‐contrast images acquired by magnified X‐ray nanotomography: one based on cross‐correlation and one based on mutual information. We found that the mutual information‐based registration algorithm was more robust than a correlation‐based method.