bluuebunny/crossref_metadata_2025 huggingface dataset:
Predictors of treatment failure on second-line antiretroviral therapy among adults in northwest Ethiopia: a multicentre retrospective follow-up study
Authors: Tsegaye Adino Tesfahun , Wubshet Mamo , Awoke Tadesse , Addis Alene Kefyalew
Published: December 2016

Background

The number of patients using second-line antiretroviral therapy (ART) has increased over time. In Ethiopia, 1.5% of HIV infected patients on ART are using a second-line regimen and little is known about its effect in this setting.

Objective

To estimate the rate and predictors of treatment failure on second-line ART among adults living with HIV in northwest Ethiopia.

Setting

An institution-based retrospective follow-up study was conducted at three tertiary hospitals in northwest Ethiopia from March to May 2015.

Participants

356 adult patients participated and 198 (55.6%) were males. Individuals who were on second-line ART for at least 6 months of treatment were included and the data were collected by reviewing their records.

Primary outcome measure

The primary outcome was treatment failure defined as immunological failure, clinical failure, death, or lost to follow-up. To assess our outcome, we used the definitions of the WHO 2010 guideline.

Result

The mean±SD age of participants at switch was 36±8.9 years. The incidence rate of failure was 61.7/1000 person years. The probability of failure at the end of 12 and 24 months were 5.6% and 13.6%, respectively. Out of 67 total failures, 42 (62.7%) occurred in the first 2 years. The significant predictors of failure were found to be: WHO clinical stage IV at switch (adjusted HR (AHR) 2.1, 95% CI 1.1 to 4.1); CD4 count <100 cells/mm3at switch (AHR 2.0, 95% CI 1.2 to 3.5); and weight change (AHR 0.92, 95% CI 0.88 to 0.95).

Conclusions

The rate of treatment failure was highest during the first 2 years of treatment. WHO clinical stage, CD4 count at switch, and change in weight were found to be predictors of treatment failure.
What determines duration of palliative care before death for patients with advanced disease? A retrospective cohort study of community and hospital palliative care provision in a large UK city
Authors: Bennett Michael I , Ziegler Lucy , Allsop Matthew , Daniel Sunitha , Hurlow Adam
Published: December 2016

Objective

For patients with advanced cancer, several randomised controlled trials have shown that access to palliative care at least 6 months before death can improve symptoms, reduce unplanned hospital admissions, minimise aggressive cancer treatments and enable patients to make choices about their end-of-life care, including exercising the choice to die at home. This study determines in a UK population the duration of palliative care before death and explores influencing factors.

Design

This retrospective cohort study analysed referrals to three specialist palliative care services; a hospital-based inpatient palliative care team, and two community-based services (hospices). For each patient referred to any of the above services we identified the date of first referral to that team and calculated the median interval between first referral and death. We also calculated how referral time varied by age, sex, diagnosis and type of palliative care service.

Participants

4650 patients referred to specialist palliative care services in Leeds UK between April 2012 and March 2014.

Results

Median age of the sample was 75 years. 3903 (84.0%) patients had a diagnosis of cancer. Age, diagnosis and place of referral were significant predictors of duration of palliative care before death. Age was independently associated (J=2 672 078, z=−392046.14, r=0.01) with duration of palliative care regardless of diagnosis. Patients over 75 years have 29 fewer days of palliative care than patients under 50. Patients with non-cancer diagnoses have 13 fewer days of palliative care than patients with cancer. Additionally, patients referred to hospital palliative care receive 24.5 fewer days palliative care than those referred to community palliative care services.

Conclusions

The current timing of referral to palliative care may limit the benefits to patients in terms of improvements in end-of-life care, particularly for older patients and patients with conditions other than cancer.
Positive predictive value of cardiac examination, procedure and surgery codes in the Danish National Patient Registry: a population-based validation study
Authors: Adelborg Kasper , Sundbøll Jens , Munch Troels , Frøslev Trine , Sørensen Henrik Toft , Bøtker Hans Erik , Schmidt Morten
Published: December 2016

Objective

Danish medical registries are widely used for cardiovascular research, but little is known about the data quality of cardiac interventions. We computed positive predictive values (PPVs) of codes for cardiac examinations, procedures and surgeries registered in the Danish National Patient Registry during 2010–2012.

Design

Population-based validation study.

Setting

We randomly sampled patients from 1 university hospital and 2 regional hospitals in the Central Denmark Region.

Participants

1239 patients undergoing different cardiac interventions.

Main outcome measure

PPVs with medical record review as reference standard.

Results

A total of 1233 medical records (99% of the total sample) were available for review. PPVs ranged from 83% to 100%. For examinations, the PPV was overall 98%, reflecting PPVs of 97% for echocardiography, 97% for right heart catheterisation and 100% for coronary angiogram. For procedures, the PPV was 98% overall, with PPVs of 98% for thrombolysis, 92% for cardioversion, 100% for radiofrequency ablation, 98% for percutaneous coronary intervention, and 100% for both cardiac pacemakers and implantable cardiac defibrillators. For cardiac surgery, the overall PPVs was 99%, encompassing PPVs of 100% for mitral valve surgery, 99% for aortic valve surgery, 98% for coronary artery bypass graft surgery, and 100% for heart transplantation. The accuracy of coding was consistent within age, sex, and calendar year categories, and the agreement between independent reviewers was high (99%).

Conclusions

Cardiac examinations, procedures and surgeries have high PPVs in the Danish National Patient Registry.
Gut feelings in the diagnostic process of Spanish GPs: a focus group study
Authors: Oliva Bernardino , March Sebastià , Gadea Cristina , Stolper Erik , Esteva Magdalena
Published: December 2016

Objectives

The gut feelings of doctors can act as triggers and modulators of the diagnostic process. This study explored the existence, significance, determinants and triggers of gut feelings among Spanish general practitioners.

Design

Qualitative study using focus groups. Thematic content analysis.

Setting

Primary healthcare centres in Majorca (Spain).

Participants

20 purposively sampled general practitioners working in Majorca.

Results

General practitioners were aware of the existence of gut feelings in their diagnostic reasoning process and recognised 2 kinds of gut feelings: a sense of alarm and a sense of reassurance. A previous physician–patient relationship and the physician's experience had a strong perceived influence on the appearance of gut feelings. The physicians attached great significance to gut feelings, and considered them as a characteristic of the primary care working style and as a tool available in their diagnostic process. The physicians thought that the notion of gut feelings and their relevance can be transmitted to students and trainees. They tended to follow their gut feelings, although they were not sure of their accuracy.

Conclusions

Spanish general practitioners in our study recognise the presence and role of gut feelings in their diagnostic reasoning process. Future research should examine the diagnostic accuracy of gut feelings and how to teach about gut feelings in the training of general practitioners.
Supporting underserved patients with their medicines: a study protocol for a patient/professional coproduced education intervention for community pharmacy staff to improve the provision and delivery of Medicine Use Reviews (MURs)
Authors: Latif Asam , Pollock Kristian , Anderson Claire , Waring Justin , Solomon Josie , Chen Li-Chia , Anderson Emma , Gulzar Sulma , Abbasi Nasa , Wharrad Heather
Published: December 2016

Introduction

Community pharmacy increasingly features in global strategies to modernise the delivery of primary healthcare. Medicine Use Reviews (MURs) form part of the English Government's medicines management strategy to improve adherence and reduce medicine waste. MURs provide space for patient–pharmacist dialogue to discuss the well-known problems patients experience with medicine taking. However, ‘underserved’ communities (eg, black and minority ethnic communities, people with mental illness), who may benefit the most, may not receive this support. This study aims to develop, implement and evaluate an e-learning education intervention which is coproduced between patients from underserved communities and pharmacy teams to improve MUR provision.

Methods and analysis

This mixed-methods evaluative study will involve a 2-stage design. Stage 1 involves coproduction of an e-learning resource through mixed patient–professional development (n=2) and review (n=2) workshops, alongside informative semistructured interviews with patients (n=10) and pharmacy staff (n=10). Stage 2 involves the implementation and evaluation of the intervention with community pharmacy staff within all community pharmacies within the Nottinghamshire geographical area (n=237). Online questionnaires will be completed at baseline and postintervention (3 months) to assess changes in engagement with underserved communities and changes in self-reported attitudes and behaviour. To triangulate findings, 10 pharmacies will record at baseline and postintervention, details of actual numbers of MURs performed and the proportion that are from underserved communities. Descriptive and inferential statistics will be used to analyse the data. The evaluation will also include a thematic analysis of one-to-one interviews with pharmacy teams to explore the impact on clinical practice (n=20). Interviews with patients belonging to underserved communities, and who received an MUR, will also be conducted (n=20).

Ethics and dissemination

The study has received ethical approval from the NHS Research Ethics Committee (East Midlands–Derby) and governance clearance through the NHS Health Research Authority. Following the evaluation, the educational intervention will be freely accessible online.
Young people's experiences of persistent musculoskeletal pain, needs, gaps and perceptions about the role of digital technologies to support their co-care: a qualitative study
Authors: Slater Helen , Jordan Joanne E , Chua Jason , Schütze Robert , Wark John D , Briggs Andrew M
Published: December 2016

Objective

To investigate young people's experiences of persistent musculoskeletal pain, including care needs and current service gaps as well as perceptions about the role of digital technologies to support their co-care.

Methods

A qualitative study employing two independent data collection modes: in-depth individual semistructured interviews and focus groups.

Setting

Community settings throughout Australia.

Participants

Participants were included if they had experienced persistent musculoskeletal pain of >3-month duration with an average of ≥3 on the visual analogue scale over the preceding 3 months, including non-specific conditions (eg, low back pain) and specific conditions (eg, juvenile idiopathic arthritis and other systemic arthritides), with/without pre-existing or current diagnosed mental health conditions. 23 young people (87.0% women; mean (SD) age: 20.8 (2.4) years) from across 6 Australian jurisdictions participated. Almost two-thirds of participants with persistent musculoskeletal pain reported comorbid mental health conditions.

Main outcome measures

Inductive and deductive approaches to analyse and derive key themes from verbatim transcripts.

Results

Participants described their daily experiences of living with persistent musculoskeletal pain, their fears and the challenges imposed by the invisibility of pain, and the two-way relationship between their pain and mental well-being. A lack of relevant and accessible information and resources tailored to young people's unique needs, integrated and youth-relevant healthcare services and adequately skilled healthcare practitioners were identified as key care gaps. Participants strongly advocated for the use of digital technologies to improve access to age-appropriate resources and support for co-care.

Conclusions

Young people living with persistent musculoskeletal pain described the absence of age-appropriate pain services and clearly articulated their perceptions on the role of, and opportunities provided by, digital technologies to connect with and support improved pain healthcare. Innovative and digitally-enabled models of pain care are likely to be helpful for this group.
Grading the quality of evidence in complex interventions: a guide for evidence-based practitioners
Authors: Murad M Hassan , Almasri Jehad , Alsawas Mouaz , Farah Wigdan
Published: December 2016

Evidence-based practitioners who want to apply evidence from complex interventions to the care of their patients are often challenged by the difficulty of grading the quality of this evidence. Using the GRADE (Grading of Recommendations, Assessment, Development and Evaluation) approach and an illustrative example, we propose a framework for evaluating the quality of evidence that depends on obtaining feedback from the evidence user (eg, guideline panel) to inform: (1) proper framing of the question, (2) judgements about directness and consistency of evidence and (3) the need for additional contextual and qualitative evidence. Using this framework, different evidence users and based on their needs would consider the same evidence as high, moderate, low or very low.
Detection rate of serrated polyps and serrated polyposis syndrome in colorectal cancer screening cohorts: a European overview
Authors: IJspeert J E G , Bevan R , Senore C , Kaminski M F , Kuipers E J , Mroz A , Bessa X , Cassoni P , Hassan C , Repici A , Balaguer F , Rees C J , Dekker E
Published: December 2016

Objective

The role of serrated polyps (SPs) as colorectal cancer precursor is increasingly recognised. However, the true prevalence SPs is largely unknown. We aimed to evaluate the detection rate of SPs subtypes as well as serrated polyposis syndrome (SPS) among European screening cohorts.

Methods

Prospectively collected screening cohorts of ≥1000 individuals were eligible for inclusion. Colonoscopies performed before 2009 and/or in individuals aged below 50 were excluded. Rate of SPs was assessed, categorised for histology, location and size. Age–sex–standardised number needed to screen (NNS) to detect SPs were calculated. Rate of SPS was assessed in cohorts with known colonoscopy follow-up data. Clinically relevant SPs (regarded as a separate entity) were defined as SPs ≥10 mm and/or SPs >5 mm in the proximal colon.

Results

Three faecal occult blood test (FOBT) screening cohorts and two primary colonoscopy screening cohorts (range 1.426–205.949 individuals) were included. Rate of SPs ranged between 15.1% and 27.2% (median 19.5%), of sessile serrated polyps between 2.2% and 4.8% (median 3.3%) and of clinically relevant SPs between 2.1% and 7.8% (median 4.6%). Rate of SPs was similar in FOBT-based cohorts as in colonoscopy screening cohorts. No apparent association between the rate of SP and gender or age was shown. Rate of SPS ranged from 0% to 0.5%, which increased to 0.4% to 0.8% after follow-up colonoscopy.

Conclusions

The detection rate of SPs is variable among screening cohorts, and standards for reporting, detection and histopathological assessment should be established. The median rate, as found in this study, may contribute to define uniform minimum standards for males and females between 50 and 75 years of age.
Cox-2-Dependent and Independent Effects of Cox-2 Inhibitors and Nsaids on Proatherogenic Changes in Human Monocytes/Macrophages
Authors: Voloshyna Iryna , Kasselman Lora J , Carsons Steven E , Littlefield Michael J , Gomolin Irving H , De Leon Joshua , Reiss Allison B
Published: December 2016

It is the second decade of controversy regarding the cardiovascular effects of cyclo-oxygenase-2 (COX-2) inhibitors. At this time, celecoxib is the only available COX-2-specific inhibitor for treatment of pain and inflammation. Therefore, the present study was designed primarily to determine the impact of celecoxib on cholesterol handling (uptake via scavenger receptors and efflux from the cells) and foam cell formation in human THP-1 macrophages, followed by comparison to rofecoxib and other non-steroidal anti-inflammatory drugs (NSAIDs). THP-1 human macrophages and peripheral blood mononuclear cells were incubated with: celecoxib, rofecoxib, naproxen (at 5, 10, 25 µM) and acetaminophen (0.5 mM, 1 mM)±oxidized low-density lipoprotein (oxLDL, 25 µg/mL). Scavenger receptors: CD36, LOX-1, SR-A1, and CXCL16 and cholesterol efflux proteins: ATP-binding cassette transporter (ABC) A1 and G1, and 27-hydroxylase were detected. The adhesion of monocytes to cultured endothelial cells with/ without COX-2 inhibitors/NSAIDs was also analyzed. The presence of celecoxib and rofecoxib (at high concentrations) significantly decreased expression of 27-hydroxylase and ABCA1, interfering with normal cholesterol outflow from macrophages. Acetaminophen and the non-specific COX inhibitor naproxen had no significant effect on these proteins. Only celecoxib had a profound effect on the class B scavenger receptor CD36 and the class E receptor LOX1. We demonstrate that in contrast to celecoxib, rofecoxib and naproxen increased adhesive properties of monocytes to endothelial cells. This work might contribute to our understanding of multiple mechanisms underlying elevated cardiovascular risk upon the use of COX-2 inhibitors and uncover new possibilities to enhance the safety profile of existing COX-2 inhibitors.
Concomitant coiling reduces metalloproteinase levels in flow diverter-treated aneurysms but anti-inflammatory treatment has no effect
Authors: Thielen Evan , McClure Megan , Rouchaud Aymeric , Ding Yong-Hong , Dai Daying , Schroeder Dana , Cebral Juan , Kallmes David F , Kadirvel Ramanathan
Published: December 2016

Background and purpose

Flow diverters (FD) can cause rare but devastating delayed aneurysm ruptures in which matrix metalloproteinases (MMPs) have been potentially implicated. Concomitant coiling or anti-inflammatory medications have been proposed to prevent the risk of delayed ruptures. The aim of this study was to evaluate concomitant coiling and ciclosporin in regulating the expression of MMPs in FD-treated aneurysms.

Materials and methods

Elastase-induced aneurysms were created in 20 rabbits. Aneurysms were treated with (1) FD alone; (2) FD with concomitant coiling; (3) FD+ ciclosporin; or (4) left untreated as controls. At sacrifice, MMP levels were analyzed by zymography. Kruskal–Wallis one-way non-parametric ANOVA was performed for each enzyme. If significant results were observed for the Kruskal–Wallis test, pairwise group comparisons were performed using Dunn's test with Bonferroni multiple-testing correction.

Results

Significant differences were observed among groups for pro-MMP9 (p=0.0337). Pairwise comparison demonstrated higher levels of pro-MMP9 with concomitant coiling compared with untreated aneurysms (p=0.012), with higher though not significantly different levels of pro-MMP9 in FD with concomitant coiling versus FD alone. While not statistically significant, trends were noted regarding differences in active-MMP9 across groups, with a lower level of active-MMP9 with concomitant coiling compared with the other FD groups. No significant differences were observed for pro- or active-MMP2 across groups, or for FD + ciclosporin compared with FD alone.

Conclusions

FD implantation increases the level of pro-MMP9 expression in aneurysms. Provocative trends regarding modulation of active-MMP9 expression with concomitant coiling suggest the need for larger confirmatory preclinical studies. Anti-inflammatory treatment with ciclosporin appears to have a minimal biological effect.

Trial registration number

R01NS076491
Long-term efficacy and safety of tocilizumab in giant cell arteritis and large vessel vasculitis
Authors: Evans Jobie , Steel Lauren , Borg Frances , Dasgupta Bhaskar
Published: December 2016

Giant cell arteritis (GCA) is a chronic systemic vasculitis affecting large-sized and medium-sized vessels. Glucocorticoids are currently the mainstay of treatment for GCA and associated large vessel vasculitis (LVV) but are associated with frequent adverse events. Methotrexate has only demonstrated a modest benefit while anti-TNF biological agents (infliximab and etanercept) have been inefficacious. Elevated levels of interleukin-6 (IL-6), a proinflammatory cytokine, has been associated with GCA. Tocilizumab (TCZ), a humanised antihuman IL-6 receptor antibody, has been used successfully in several reports as a treatment for GCA and LVV. We report the potentially long-term successful use of TCZ in 8 cases of refractory LVV. All of our patients achieved a good clinical response to TCZ and C reactive protein reduced from an average of 70.3 to 2.5. In all cases, the glucocorticoid dose was reduced, from an average of 24.6 mg prednisolone prior to TCZ treatment to 4.7 mg, indicating that TCZ may enable a reduction in glucocorticoid-associated adverse events. However, regular TCZ administration was needed for disease control in most cases. TCZ was discontinued in one case due to the development of an empyema indicating the need for careful monitoring of infection when using this treatment.
Effectiveness of four dynamic treatment strategies in patients with anticitrullinated protein antibody-negative rheumatoid arthritis: a randomised trial
Authors: Akdemir G , Markusse IM , Dirven L , Riyazi N , Steup-Beekman GM , Kerstens PJSM , Lems WF , Huizinga TWJ , Allaart CF
Published: December 2016

Objective

To determine the most effective treatment strategy among anticitrullinated protein antibodies (ACPA)-negative patients with early rheumatoid arthritis.

Methods

In the BeSt study, 184 ACPA-negative patients were randomised to: (1) sequential monotherapy, (2) step-up therapy, (3) initial combination including prednisone, (4) initial combination including infliximab. Treatment was targeted at the disease activity score (DAS) ≤2.4. Early response and 10-year outcomes were compared between the four strategy-arms in ACPA-negative patients.

Results

ACPA-negative patients achieved more short-term functional improvement from initial combination therapy than when on monotherapy (at month 3, mean Health Assessment Questionnaire (HAQ) 0.71 vs 0.98, p=0.006; at month 6, 0.59 vs 0.87, p=0.004). Functional ability over time was comparable between the strategy-arms (p=0.551) with a mean HAQ of 0.6 at year 10 (p=0.580 for comparison across the strategy-arms). 10-year radiographic progression was negligible (median 0.5) and comparable between the 4 strategy-arms (p=0.082). At year 10, remission was achieved by 11/40 (28%), 9/45 (20%), 17/56 (30%) and 17/43 patients (40%) in strategy-arms 1–4, respectively (p=0.434). Over time, similar remission percentages were achieved in all strategy-arms (p=0.815). 18%, 16%, 20% and 21% in strategy-arms 1 to 4 (p=0.742) were in drug-free remission at year 10, with a median duration of 60 months across the arms.

Conclusions

Initial combination therapy with methotrexate, sulfasalazine and prednisone, or methotrexate and infliximab, is the most effective treatment strategy for ACPA-negative patients, resulting in earlier functional improvement than when on initial methotrexate monotherapy. After 10 years of targeted treatment, in all strategy-arms favourable clinical outcomes were achieved and radiographic progression was limited.

Trial registration number

NTR262, NTR265.
Novel heterozygous C243Y A20/TNFAIP3 gene mutation is responsible for chronic inflammation in autosomal-dominant Behçet's disease
Authors: Shigemura Tomonari , Kaneko Naoe , Kobayashi Norimoto , Kobayashi Keiko , Takeuchi Yusuke , Nakano Naoko , Masumoto Junya , Agematsu Kazunaga
Published: December 2016

Objective

Although Behçet's disease (BD) is a chronic inflammatory disorder of uncertain aetiology, the existence of familial BD with autosomal-dominant traits suggests that a responsibility gene (or genes) exists. We investigated a Japanese family with a history of BD to search for pathogenic mutations underlying the biological mechanisms of BD.

Methods

6 patients over 4 generations who had suffered from frequent oral ulcers, genital ulcers and erythaema nodosum-like lesions in the skin were assessed. Whole-exome sequencing was performed on genomic DNA, and cytokine production was determined from stimulated mononuclear cells. Inflammatory cytokine secretion and Nod2-mediated NF-κB activation were analysed using the transfected cells.

Results

By whole-exome sequencing, we identified a common heterozygous missense mutation inA20/TNFAIP3, a gene known to regulate NF-κB signalling, for which all affected family members carried a heterozygous C243Y mutation in the ovarian tumour domain. Mononuclear cells obtained from the proband and his mother produced large amounts of interleukin 1β, IL-6 and tumour necrosis factor α (TNF-a) on stimulation as compared with those from normal controls. Although inflammatory cytokine secretion was suppressed by wild-type transfected cells, it was suppressed to a much lesser extent by mutated C243YA20/TNFAIP3-transfected cells. In addition, impaired suppression of Nod2-mediated NF-κB activation by C243YA20/TNFAIP3was observed.

Conclusions

A C243Y mutation inA20/TNFAIP3was likely responsible for increased production of human inflammatory cytokines by reduced suppression of NF-κB activation, and may have accounted for the autosomal-dominant Mendelian mode of BD transmission in this family.
Costs of early spondyloarthritis: estimates from the first 3 years of the DESIR cohort
Authors: Harvard Stephanie , Guh Daphne , Bansback Nick , Richette Pascal , Dougados Maxime , Anis Aslam , Fautrel Bruno
Published: December 2016

Objectives

To value health resource utilisation and productivity losses in DESIR, a longitudinal French cohort of 708 patients with early spondyloarthritis (SpA) enrolled between 2007 and 2010, and identify factors associated with costs in the first 3 years of follow-up.

Methods

Self-reported clinical data from DESIR and French public data were used to value health resource utilisation and productivity losses in 2013 Euros. Factors associated with costs, including and excluding biological drugs, were identified in generalised linear models using the generalised estimating equations algorithm to account for repeated observations over participants.

Results

The mean (±SD) annual cost per patient was €5004±6870 in year 1, decreasing to €4961±7457 in year 3. Patients who never received a biologic had mean 3-year total costs of €4789±6022 compared to €38 206±19 829 among those who received a biologic. Factors associated with increased total costs were peripheral arthritis (rate ratio (RR) 1.19; 95% CI 1.04 to 1.37; p<0.0001), time on biologics (RR 1.23 per month; 1.21, 1.24; p<0.0001), and average BASFI score (RR 1.18/10 point increase; 1.15, 1.25; p<0.0001). Factors associated with increased costs excluding biologics were baseline age (RR 1.10 per 5 year increase; 1.05, 1.16; p<0.0001), peripheral arthritis (RR 1.20; 1.02, 1.40; p<0.0133), time on biologics (RR 1.04 per month; 1.02, 1.05; p<0.0001), and average BASDAI score (RR 1.21 per 10 point increase; 1.16, 1.25; p<0.0001).

Conclusions

In addition to biologics, factors like age, peripheral arthritis and disease activity independently increase SpA-related costs. This study may serve as a benchmark for cost of illness among patients with early SpA in the biologic era.
Clinical joint inactivity predicts structural stability in patients with established rheumatoid arthritis
Authors: Gärtner M , Sigmund I K , Alasti F , Supp G , Radner H , Machold K , Smolen J S , Aletaha D
Published: December 2016

Objectives

Clinical joint activity is a strong predictor of joint damage in rheumatoid arthritis (RA), but progression of damage might increase despite clinical inactivity of the respective joint (silent progression). The aim of this study was to evaluate the prevalence of silent joint progression, but particularly on the patient level and to investigate the duration of clinical inactivity as a marker for non-progression on the joint level.

Methods

279 patients with RA with any radiographic progression over an observational period of 3–5 years were included. We obtained radiographic and clinical data of 22 hand/finger joints over a period of at least 3 years. Prevalence of silent progression and associations of clinical joint activity and radiographic progression were evaluated.

Results

120 (43.0%) of the patients showed radiographic progression in at least one of their joints without any signs of clinical activity in that respective joint. In only 7 (5.8%) patients, such silent joint progression would go undetected, as the remainder had other joints with clinical activity, either with (n=84; 70.0%) or without (n=29; 24.2%) accompanying radiographic progression. Also, the risk of silent progression decreases with duration of clinical activity.

Conclusions

Silent progression of a joint without accompanying apparent clinical activity in any other joint of a patient was very rare, and would therefore be most likely detected by the assessment of the patient. Thus, full clinical remission is an excellent marker of structural stability in patients with RA, and the maintenance of this state reduces the risk of progression even further.
Effects of aerobic or resistance training or both on health-related quality of life in youth with obesity: the HEARTY Trial
Authors: Goldfield Gary S. , Kenny Glen P. , Alberga Angela S. , Tulloch Heather E. , Doucette Steve , Cameron Jameason D. , Sigal Ronald J.
Published: December 2016

This study examined the effects of aerobic and resistance training, and their combination on health-related quality of life (HRQoL) in adolescents with overweight or obesity. After a 4-week run-in period, 304 (91 males, 213 females) post-pubertal adolescents aged 14–18 years, were randomized to 4 groups for 22 weeks of: aerobic training (n = 75), resistance training (n = 78), combined aerobic and resistance training (n = 75), or nonexercising control (n = 76). All participants received dietary counseling with a daily energy deficit of 250 kcal. Indicators of HRQoL such as overall HRQoL, and physical and psychosocial (an aggregate of emotional, social, and school functioning) HRQoL at baseline and 6 months postintervention were measured by the Pediatric Quality of Life questionnaire. The trial began in March 2005 and was completed in June 2011. In the intention-to-treat analyses, all groups showed significant improvements at 6 months on all HRQoL indicators. The aerobic group showed greater improvements than controls on physical HRQoL (mean differences of 5.5; 95% CI; 1.4–9.6, p = 0.009). In participants with ≥70% adherence, combined training produced greater improvements than control on overall HRQoL (mean differences of 4.8, 95% CI; 0.7–9.0, p = 0.02), physical HRQoL (mean differences of 5.8; 95% CI: 0.6–10.7; p = 0.03), social HRQoL (mean differences of 7.6; 95% CI: 1.0–14.2; p = 0.02), and school-based HRQoL (mean differences of 7.6; 95% CI: 1.0–14.2; p = 0.02). These findings highlight the potential importance of including resistance exercise into traditional aerobic exercise programs to maximize HRQoL in adolescents with obesity.
An integrated tagging model to estimate mortality rates of Albemarle Sound – Roanoke River striped bass
Authors: Harris Julianne E. , Hightower Joseph E.
Published: December 2016

We developed an integrated tagging model to estimate mortality rates and run sizes of Albemarle Sound – Roanoke River striped bass (Morone saxatilis), including (i) a multistate component for telemetered fish with a high reward external tag; (ii) tag return components for fish with a low reward external or PIT tag; and (iii) catch-at-age data. Total annual instantaneous mortality was 1.08 for resident (458–899 mm total length, TL) and 0.45 for anadromous (≥900 mm TL) individuals. Annual instantaneous natural mortality was higher for resident (0.70) than for anadromous (0.21) fish due to high summer mortality in Albemarle Sound. Natural mortality for residents was substantially higher than currently assumed for stock assessment. Monthly fishing mortality from multiple sectors (including catch-and-release) corresponded to seasonal periods of legal harvest. Run size estimates were 499 000–715 000. Results and simulation suggest increasing sample size for the multistate component increases accuracy and precision of annual estimates and low reward tags are valuable for estimating monthly fishing mortality rates among sectors. Our results suggest that integrated tagging models can produce seasonal and annual mortality estimates needed for stock assessment and management.
Curcumin protects neuronal cells against status-epilepticus-induced hippocampal damage through induction of autophagy and inhibition of necroptosis
Authors: Wang Jin , Liu Yuan , Li Xiao-Hui , Zeng Xiang-Chang , Li Jian , Zhou Jun , Xiao Bo , Hu Kai
Published: December 2016

Status epilepticus, the most severe form of epilepsy, is characterized by progressive functional and structural damage in the hippocampus, ultimately leading to the development and clinical appearance of spontaneous, recurrent seizures. Although the pathogenesis underlying epileptogenesis processes remains unclear, a substantial body of evidence has shown that status epilepticus acts as an important initial factor in triggering epileptogenesis. Notably, besides classical cell death mechanisms such as apoptosis and necrosis, 2 novel regulators of cell fate known as necroptosis and autophagy, are demonstrated to be involved in neuronal damage in various neurodegenerative and neuropsychiatric disorders. However, whether necroptosis and autophagy play a role in post-status-epilepticus rat hippocampus and other epilepsy mechanisms deserves further research effort. In addition, research is needed to determine whether compounds from traditional Chinese herbs possess antiepileptic effects through the modulation of necroptosis and autophagy. In this study, we found that curcumin, a polyphenolic phytochemical extracted from the Curcuma longa plant, protects neuronal cells against status-epilepticus-induced hippocampal neuronal damage in the lithium–pilocarpine-induced status epilepticus rat model through induction of autophagy and inhibition of necroptosis.
Nonlinearity Measurement of a Voltage Ramp Using a Digital Technique
Authors: Milik Adam , Hrynkiewicz Edward
Published: December 2016

The paper presents the idea and implementation of a digital nonlinearity measurement of a voltage ramp. The measurement process is based on evaluation of a time period between the moments when an input voltage ramp and an ideal voltage ramp reach the given value. During this period, the clock pulse train is supplied to the counter. By adjusting the pulse frequency and the circuit parameters, it is possible to obtain the nonlinearity readout in a fraction of percent directly. An automatic range determination has been presented when the reference frequency is constant. Calibration and measurement are completed for two slopes (periods) of the voltage ramp. The measurement error for the proposed method and implementation results were evaluated.
An Energy Efficient Logic Approach to Implement CMOS Full Adder
Authors: Kumar Pankaj , Sharma Rajender Kumar
Published: December 2016

An energy efficient internal logic approach for designing two 1-bit full adder cells is proposed in this work. It is based on decomposition of the full adder logic into the smaller modules. Low power, high speed and smaller area are the main features of the proposed approach. A modified power aware NAND gate, an essential entity, is also presented. The proposed full adder cells achieve 30.13% and improvement in their power delay product (PDP) metrics when compared with the best reported full adder design. Some of the popular adders and proposed adders are designed with cadence virtuoso tool with UMC 90[Formula: see text]nm technology operating at 1.2[Formula: see text]V supply voltage and UMC 55[Formula: see text]nm CMOS technology operating at 1.0[Formula: see text]V. These designs are tested on a common environment. During the experiment, it is also found that the proposed adder cells exhibit excellent signal integrity and driving capability when operated at low voltages.
On the maximal Sobolev regularity of distributions supported by subsets of Euclidean space
Authors: Hewett D. P. , Moiola A.
Published: December 2016

This paper concerns the following question: given a subset [Formula: see text] of [Formula: see text] with empty interior and an integrability parameter [Formula: see text], what is the maximal regularity [Formula: see text] for which there exists a non-zero distribution in the Bessel potential Sobolev space [Formula: see text] that is supported in [Formula: see text]? For sets of zero Lebesgue measure, we apply well-known results on set capacities from potential theory to characterize the maximal regularity in terms of the Hausdorff dimension of [Formula: see text], sharpening previous results. Furthermore, we provide a full classification of all possible maximal regularities, as functions of [Formula: see text], together with the sets of values of [Formula: see text] for which the maximal regularity is attained, and construct concrete examples for each case. Regarding sets with positive measure, for which the maximal regularity is non-negative, we present new lower bounds on the maximal Sobolev regularity supported by certain fat Cantor sets, which we obtain both by capacity-theoretic arguments, and by direct estimation of the Sobolev norms of characteristic functions. We collect several results characterizing the regularity that can be achieved on certain special classes of sets, such as [Formula: see text]-sets, boundaries of open sets, and Cartesian products, of relevance for applications in differential and integral equations.
Building Smart Cities in China: Problems and Countermeasures
Authors: CONG Xiaonan , LIU Zhiyan , WANG Yi
Published: December 2016

This paper argues that although the construction of smart cities in China has followed other countries closely, the popularization of concepts, the construction mechanisms and achievements are still behind the advanced countries. The pilot and demonstration pattern in the Chinese construction of smart cities has several advantages, such as wide coverage of cities, large investment funds, diversity of applications and good coordination among different agents. Utilizing this pattern is conducive to exploring a suitable way to construct China's smart cities, and narrow the gap between China and the advanced countries. The paper summarizes eight barriers in the construction of smart cities in China, and offers some proposals on promoting the levels of construction regarding several aspects, such as forming the construction pattern, expanding the application system, strengthening the investment on R&D, providing the support of the industry, and integrating pilot projects.
Outline of a Permian tetrapod footprint ichnostratigraphy
Authors: Voigt Sebastian , Lucas Spencer G.
Published: December 2016

Tetrapod footprints are among the most common fossil remains in continental Permian strata and thus are of biostratigraphic interest. Based on the vertical distribution of the 13 best-known Permian tetrapod ichnotaxa, three footprint biochrons are suggested for the period: (1)
Dromopus
– latest Carboniferous (approximately Gzhelian) to late Early Permian (approximately Artinskian), representing ichnoassemblages dominated by tracks of temnospondyls, reptiliomorphs, pelycosaurs and early diapsids; (2)
Erpetopus
– late Early Permian (approximately Kungurian) to late Middle Permian (approximately Capitanian), representing ichnoassemblages dominated by tracks of non-diapsid eureptiles; and (3)
Paradoxichnium
– Late Permian (Wuchiapingian and Changhsingian), representing ichnoassemblages dominated by tracks of medium- and large-sized parareptiles, non-diapsid eureptiles and early saurians. This is the most conservative ichnostratigraphic concept, and it may be possible to refine it to almost stage-level resolution by future comprehensive analysis, especially of Permian captorhinomorph and therapsid footprints. Other major tasks to improve Permian tetrapod footprint ichnostratigraphy include enhanced knowledge of Middle Permian tetrapod footprints, and clarification of the palaeoenvironmental factors that may control the distribution of tetrapod footprints in space and time.
Global Permian brachiopod biostratigraphy: an overview
Authors: Shen Shu-Zhong
Published: December 2016

Establishing a Permian brachiopod biochronological scheme for global correlation is difficult because of strong provincialism during the Permian. In this paper, a brief overview of brachiopod successions in five major palaeobiogeographical realms/zones is provided. For Gondwanaland and peri-Gondwanan regions including Cimmerian blocks,
Bandoproductus
and
Punctocyrtella
(or
Cyrtella
) are characteristic of the lower Cisuralian, as is
Cimmeriella
for the middle Cisuralian. As the Cimmerian blocks continued drifting north during the late Kungurian, accompanied by climate amelioration, contemporaneous brachiopods inhabiting these blocks showed a distinct shift from cold-water to mixed or warm-water affinities. However, coeval brachiopods in the Northern Transitional Zone (NTZ) are characterized by warm-water faunas and are associated with fusulinids in the lower Cisuralian. The Guadalupian brachiopods of the NTZ were clearly mixed between the Boreal and palaeoequatorial affinities. The end-Guadalupian is marked by the disappearance of a few characteristic genera, such as
Vediproductus
,
Neoplicatifera
and
Urushtenoidea
, in the Palaeotethyan region. The onset of the end-Permian mass extinction in the latest Changhsingian is clearly exhibited by the occurrence of the dwarfed and thin-shelled brachiopods commonly containing
Paracrurithyris
.
The Permian chronostratigraphic scale: history, status and prospectus
Authors: Lucas Spencer G. , Shen Shu-Zhong
Published: December 2016

In 1841, Murchison coined the term Permian for strata in the Russian Urals. Recognition of the Permian outside of Russia and central Europe soon followed, but it took about a century for the Permian to be accepted globally as a distinct geological system. The work of the Subcommission on Permian Stratigraphy began in the 1970s and resulted in current recognition of nine Permian stages in three series: the Cisuralian (lower Permian) – Asselian, Sakmarian, Artinskian and Kungurian; the Guadalupian (middle Permian) – Roadian, Wordian and Capitanian; and the Lopingian (upper Permian) – Wuchiapingian and Changhsingian. The 1990s saw the rise of Permian conodont biostratigraphy, so that all Permian Global Stratigraphic Sections and Points (GSSPs) use conodont evolutionary events as the primary signal for correlation.

Issues in the development of a Permian chronostratigraphic scale include those of stability and priority of nomenclature and concepts, disagreements over changing taxonomy, ammonoid v. fusulinid v. conodont biostratigraphy, differences in the perceived significance of biotic events for chronostratigraphic classification, and correlation problems between provinces. Further development of the Permian chronostratigraphic scale should focus on GSSP selection for the remaining, undefined stage bases, definition and characterization of substages, and further integration of the Permian chronostratigraphic scale with radioisotopic, magnetostratigraphic and chemostratigraphic tools for calibration and correlation.
A global review of Permian macrofloral biostratigraphical schemes
Authors: Cleal Christopher J.
Published: December 2016

Separate biostratigraphical schemes have been developed for Permian macrofloras in the five main phytochoria (palaeokingdoms), reflecting the essential lack of overlap in taxonomic composition. In Europe two biozones are normally recognized, in North America three zones, in Cathaysia three or four zones, in Gondwana four zones and in Angara five zones. The stratigraphical resolution tends to be far less than that of palynology, and up to an order of magnitude coarser than the macrofloral biozones of the Pennsylvanian subsystem. This is probably due, at least in part, to the lack of rigor in the way that the Permian macrofloral zones have been defined. Nevertheless, the existing zones do provide evidence of the overarching trajectory of change in vegetation through the Permian Period, as it responded at all palaeolatitudes to a combination of climate change, large-scale volcanic eruptions and tectonically driven landscape changes.
Late Pennsylvanian–Early Triassic conchostracan biostratigraphy: a preliminary approach
Authors: Schneider Joerg W. , Scholze Frank
Published: December 2016

Conchostracans are one of the most common fossil animal groups of continental deposits from late Palaeozoic to modern times. Their habitats have ranged from perennial lakes of the Carboniferous and Early Permian to seasonal playa lakes and temporary ponds from the late Early Permian into the Triassic, where they could form mass occurrences. This, together with relatively high speciation rates, makes them ideal guide fossils, especially in otherwise fossil-poor wet and dry red beds. Based on material and data collected since the 1980s from both surface outcrops and well cores in central Europe, a preliminary conchostracan zonation is proposed. We used a conservative approach, erecting assemblage zones comprising two or three species instead of species-range zones with only one or, sometimes, two forms. Assemblage zones are more robust and provide more reliability for each delineated time interval. Isotopically dated occurrences of conchostracan zone species, or co-occurrences of conchostracans, insect zone species and marine index fossils such as conodonts and fusulinids, allow us to correlate our assemblage zones with the marine Standard Global Chronostratigraphic Scale.
A geomagnetic polarity timescale for the Permian, calibrated to stage boundaries
Authors: Hounslow Mark W. , Balabanov Yuri P.
Published: December 2016

The reverse polarity Kiaman Superchron has strong evidence for at least three, or probably four, normal magnetochrons during the early Permian. Normal magnetochrons are during the early Asselian (base CI1r.1n at 297.94±0.33 Ma), late Artinskian (CI2n at 281.24±2.3 Ma), mid-Kungurian (CI3n at 275.86±2.0 Ma) and Roa"dian (CI3r.an at 269.54±1.6 Ma). The mixed-polarity Illawarra Superchron begins in the early Wordian at 266.66±0.76 Ma. The Wordian–Capitanian interval is biased to normal polarity, but the basal Wuchiapingian begins the beginning of a significant reverse polarity magnetochron LP0r, with an overlying mixed-polarity interval through the later Lopingian. No significant magnetostratigraphic data gaps exist in the Permian geomagnetic polarity record. The early Cisuralian magnetochrons are calibrated to a succession of fusulinid zones, the later Cisuralian and Guadalupian to a conodont and fusulinid biostratigraphy, and Lopingian magnetochrons to conodont zonations. Age calibration of the magnetochrons is obtained through a Bayesian approach using 35 radiometric dates, and 95% confidence intervals on the ages and chron durations are obtained. The dating control points are most numerous in the Gzhelian–Asselian, Wordian and Changhsingian intervals. This significant advance should provide a framework for better correlation and dating of the marine and non-marine Permian.