bluuebunny/crossref_metadata_2025 huggingface dataset:
PRESTASI PEMBAKARAN MINYAK JATROPHA SEBAGAI BAHAN API CECAIR BIODIESEL PADA SISTEM PEMBAKAR BERBAHAN API CECAIR
Authors: Rahim Muhammad Roslan , Yusof Mustafa , Azman Aidil Hafiz , Mohd Jaafar Mohammad Nazri
Published: August 2017

The world is passing through a phase of sustainable modernization and industrial development day by day. As a result, there is an increasing number of vehicles used and heat engines demands in the market. However, energy sources used in these engines are limited and decreasing gradually. This situation leads to evolution of alternative sources to viable fuel for diesel engine. Biodiesel is seen as an alternative fuel for diesel engine combustion.  The esters of vegetable or plant oil and animal fats are known as biodiesel. This article investigates the prospect of producing biodiesel from Jatropha oil. Jatropha curcas oil is a renewable non-edible plant. The seeds of Jatropha contain 50-60% oil. In this study, the oil has been converted to biodiesel by a well-known two-step, acid-base catalytic transesterification and used in diesel burner for performance evaluation. Biodiesel used in this study is a blend of diesel and Jatropha biodiesel. The performance of burner system using Jatropha biodiesel is based on its temperature profile and emissions generated such as nitrous oxide (NOx), sulphur dioxide (SO2) and carbon monoxide (CO).  A reduction of 50% was achieved for both CO dan SO2 when burning Jatropha biodiesel compared to burning diesel.
HOME-BASED ANKLE REHABILITATION SYSTEM: LITERATURE REVIEW AND EVALUATION
Authors: Ee Chin Lim Ch , Basah Shafriza Nisha , Affandi Marwan , Shah Muhammad Nazrin , Yaacob Sazali , Ewe Juan Yeap , Din Mohamad Yazid
Published: August 2017

Ankle sprain Injury is one of the most common ankle injuries due to domestic or sporting accidents. There is a need for greater demand for quick and effective ankle rehabilitation system (ARS). Nowadays, research on ARS has gained a great attention than manual clinical method in medical areas such as orthopedic injuries, pediatrics sport medicine and industrial services. It can improve the treatment conditions by reducing the dependency of doctors’ supervision, help patient with less movable to have home-based rehab exercise and help to speeds up recovery. There are currently available ARS that can provide effective ankle rehabilitation treatment such as Visual, Non-Visual and Robot-aided. In this paper, the critical review of ARS is conducted to evaluate the effectiveness of ARS in terms of provided setting criteria. The strengths, weaknesses, opportunities and threats of each ARS is discussed and compared to identify the most suitable home application of ARS for ankle sprain patient. From the comparison, the most suitable home application ARS is the visual marker-less based ARS system which give user-friendly, efficiency, validity in performance and cheaper cost.
On mod local-global compatibility for in the ordinary case
Authors: Herzig Florian , Le Daniel , Morra Stefano
Published: August 2017

Suppose that $F/F^{+}$ is a CM extension of number fields in which the prime $p$ splits completely and every other prime is unramified. Fix a place $w|p$ of $F$. Suppose that $\overline{r}:\operatorname{Gal}(\overline{F}/F)\rightarrow \text{GL}_{3}(\overline{\mathbb{F}}_{p})$ is a continuous irreducible Galois representation such that $\overline{r}|_{\operatorname{Gal}(\overline{F}_{w}/F_{w})}$ is upper-triangular, maximally non-split, and generic. If $\overline{r}$ is automorphic, and some suitable technical conditions hold, we show that $\overline{r}|_{\operatorname{Gal}(\overline{F}_{w}/F_{w})}$ can be recovered from the $\text{GL}_{3}(F_{w})$-action on a space of mod $p$ automorphic forms on a compact unitary group. On the way we prove results about weights in Serre’s conjecture for $\overline{r}$, show the existence of an ordinary lifting of $\overline{r}$, and prove the freeness of certain Taylor–Wiles patched modules in this context. We also show the existence of many Galois representations $\overline{r}$ to which our main theorem applies.
Increased adaptive immune responses and proper feedback regulation protect against clinical dengue
Authors: Simon-Lorière Etienne , Duong Veasna , Tawfik Ahmed , Ung Sivlin , Ly Sowath , Casadémont Isabelle , Prot Matthieu , Courtejoie Noémie , Bleakley Kevin , Buchy Philippe , Tarantola Arnaud , Dussart Philippe , Cantaert Tineke , Sakuntabhai Anavaj
Published: August 2017

Increased activation of adaptive immunity and proper feedback mechanisms can eliminate dengue viral infection without clinical symptoms.
Rewriting the genome in human embryos
Authors: Byrne Leah C.
Published: August 2017

Researchers have edited the genome of human embryos to correct dominant myocardial disease.
Deterring zoster
Authors: Miner Jonathan J.
Published: August 2017

Germline mutations in RNA polymerase III cause susceptibility to life-threatening varicella zoster infection.
Whole-Genome Sequencing of Bacterial Pathogens: the Future of Nosocomial Outbreak Analysis
Authors: Quainoo Scott , Coolen Jordy P. M. , van Hijum Sacha A. F. T. , Huynen Martijn A. , Melchers Willem J. G. , van Schaik Willem , Wertheim Heiman F. L.
Published: August 2017

Outbreaks of multidrug-resistant bacteria present a frequent threat to vulnerable patient populations in hospitals around the world. Intensive care unit (ICU) patients are particularly susceptible to nosocomial infections due to indwelling devices such as intravascular catheters, drains, and intratracheal tubes for mechanical ventilation. The increased vulnerability of infected ICU patients demonstrates the importance of effective outbreak management protocols to be in place. Understanding the transmission of pathogens via genotyping methods is an important tool for outbreak management. Recently, whole-genome sequencing (WGS) of pathogens has become more accessible and affordable as a tool for genotyping. Analysis of the entire pathogen genome via WGS could provide unprecedented resolution in discriminating even highly related lineages of bacteria and revolutionize outbreak analysis in hospitals. Nevertheless, clinicians have long been hesitant to implement WGS in outbreak analyses due to the expensive and cumbersome nature of early sequencing platforms. Recent improvements in sequencing technologies and analysis tools have rapidly increased the output and analysis speed as well as reduced the overall costs of WGS. In this review, we assess the feasibility of WGS technologies and bioinformatics analysis tools for nosocomial outbreak analyses and provide a comparison to conventional outbreak analysis workflows. Moreover, we review advantages and limitations of sequencing technologies and analysis tools and present a real-world example of the implementation of WGS for antimicrobial resistance analysis. We aimed to provide health care professionals with a guide to WGS outbreak analysis that highlights its benefits for hospitals and assists in the transition from conventional to WGS-based outbreak analysis.
Inhibition of Amebic Lysosomal Acidification Blocks Amebic Trogocytosis and Cell Killing
Authors: Gilmartin Allissia A. , Ralston Katherine S. , Petri William A.
Published: August 2017

Entamoeba histolytica
ingests fragments of live host cells in a nibbling-like process termed amebic trogocytosis. Amebic trogocytosis is required for cell killing and contributes to tissue invasion, which is a hallmark of invasive amebic colitis. Work done prior to the discovery of amebic trogocytosis showed that acid vesicles are required for amebic cytotoxicity. In the present study, we show that acidified lysosomes are required for amebic trogocytosis and cell killing. Interference with lysosome acidification using ammonium chloride, a weak base, or concanamycin A, a vacuolar H
+
ATPase inhibitor, decreased amebic trogocytosis and amebic cytotoxicity. Our data suggest that the inhibitors do not impair the ingestion of an initial fragment but rather block continued trogocytosis and the ingestion of multiple fragments. The acidification inhibitors also decreased phagocytosis, but not fluid-phase endocytosis. These data suggest that amebic lysosomes play a crucial role in amebic trogocytosis, phagocytosis, and cell killing.

IMPORTANCE
E. histolytica
is a protozoan parasite that is prevalent in low-income countries, where it causes potentially fatal diarrhea, dysentery, and liver abscesses. Tissue destruction is a hallmark of invasive
E. histolytica
infection. The parasite is highly cytotoxic to a wide range of human cells, and parasite cytotoxic activity is likely to drive tissue destruction.
E. histolytica
is able to kill human cells through amebic trogocytosis. This process also contributes to tissue invasion. Trogocytosis has been observed in other organisms; however, little is known about the mechanism in any system. We show that interference with lysosomal acidification impairs amebic trogocytosis, phagocytosis, and cell killing, indicating that amebic lysosomes are critically important for these processes.
Functional Constraints on Replacing an Essential Gene with Its Ancient and Modern Homologs
Authors: Kacar Betül , Garmendia Eva , Tuncbag Nurcan , Andersson Dan I. , Hughes Diarmaid
Published: August 2017

Genes encoding proteins that carry out essential informational tasks in the cell, in particular where multiple interaction partners are involved, are less likely to be transferable to a foreign organism. Here, we investigated the constraints on transfer of a gene encoding a highly conserved informational protein, translation elongation factor Tu (EF-Tu), by systematically replacing the endogenous
tufA
gene in the
Escherichia coli
genome with its extant and ancestral homologs. The extant homologs represented
tuf
variants from both near and distant homologous organisms. The ancestral homologs represented phylogenetically resurrected
tuf
sequences dating from 0.7 to 3.6 billion years ago (bya). Our results demonstrate that all of the foreign
tuf
genes are transferable to the
E. coli
genome, provided that an additional copy of the EF-Tu gene,
tufB
, remains present in the
E. coli
genome. However, when the
tufB
gene was removed, only the variants obtained from the gammaproteobacterial family (extant and ancestral) supported growth which demonstrates the limited functional interchangeability of
E. coli tuf
with its homologs. Relative bacterial fitness correlated with the evolutionary distance of the extant
tuf
homologs inserted into the
E. coli
genome. This reduced fitness was associated with reduced levels of EF-Tu and reduced rates of protein synthesis. Increasing the expression of
tuf
partially ameliorated these fitness costs. In summary, our analysis suggests that the functional conservation of protein activity, the amount of protein expressed, and its network connectivity act to constrain the successful transfer of this essential gene into foreign bacteria.

IMPORTANCE
Horizontal gene transfer (HGT) is a fundamental driving force in bacterial evolution. However, whether essential genes can be acquired by HGT and whether they can be acquired from distant organisms are very poorly understood. By systematically replacing
tuf
with ancestral homologs and homologs from distantly related organisms, we investigated the constraints on HGT of a highly conserved gene with multiple interaction partners. The ancestral homologs represented phylogenetically resurrected
tuf
sequences dating from 0.7 to 3.6 bya. Only variants obtained from the gammaproteobacterial family (extant and ancestral) supported growth, demonstrating the limited functional interchangeability of
E. coli tuf
with its homologs. Our analysis suggests that the functional conservation of protein activity, the amount of protein expressed, and its network connectivity act to constrain the successful transfer of this essential gene into foreign bacteria.
Multifunctional Involvement of a C2H2 Zinc Finger Protein (PbZfp) in Malaria Transmission, Histone Modification, and Susceptibility to DNA Damage Response
Authors: Gopalakrishnan Anusha M. , Aly Ahmed S. I. , Aravind L. , Kumar Nirbhay
Published: August 2017

In sexually reproducing organisms, meiosis is an essential step responsible for generation of haploid gametes from diploid somatic cells. The quest for understanding regulatory mechanisms of meiotic recombination in
Plasmodium
led to identification of a gene encoding a protein that contains 11 copies of C
2
H
2
zinc fingers (ZnF). Reverse genetic approaches were used to create
Plasmodium berghei
parasites either lacking expression of full-length
Plasmodium berghei
zinc finger protein (PbZfp) (knockout [KO]) or expressing PbZfp lacking C-terminal zinc finger region (truncated [Trunc]). Mice infected with KO parasites survived two times longer (
P
< 0.0001) than mice infected with wild-type (WT) parasites. In mosquito transmission experiments, the infectivity of KO and Trunc parasites was severely compromised (>95% oocyst reduction). KO parasites revealed a total lack of trimethylation of histone 3 at several lysine residues (K4, K27, and K36) without any effect on acetylation patterns (H3K9, H3K14, and H4K16). Reduced DNA damage and reduced expression of topoisomerase-like Spo11 in the KO parasites with normal Rad51 expression further suggest a functional role for PbZfp during genetic recombination that involves DNA double-strand break (DSB) formation followed by DNA repair. These finding raise the possibility of some convergent similarities of PbZfp functions to functions of mammalian PRDM9, also a C
2
H
2
ZnF protein with histone 3 lysine 4 (H3K4) methyltransferase activity. These functions include the major role played by the latter in binding recombination hotspots in the genome during meiosis and trimethylation of the associated histones and subsequent chromatin recruitment of topoisomerase-like Spo11 to catalyze DNA DSB formation and DMC1/Rad51-mediated DNA repair and homologous recombination.

IMPORTANCE
Malaria parasites are haploid throughout their life cycle except for a brief time period when zygotes are produced as a result of fertilization between male and female gametes during transmission through the mosquito vector. The reciprocal recombination events that follow zygote formation ensure orderly segregation of homologous chromosomes during meiosis, creating genetic diversity among offspring. Studies presented in the current manuscript identify a novel C2H2 ZnF-containing protein exhibiting multifunctional roles in parasite virulence, mosquito transmission, and homologous recombination during meiosis. Understanding the transmission biology of malaria will result in the identification of novel targets for transmission-blocking intervention approaches.
Metabolic Network Analysis and Metatranscriptomics Reveal Auxotrophies and Nutrient Sources of the Cosmopolitan Freshwater Microbial Lineage acI
Authors: Hamilton Joshua J. , Garcia Sarahi L. , Brown Brittany S. , Oyserman Ben O. , Moya-Flores Francisco , Bertilsson Stefan , Malmstrom Rex R. , Forest Katrina T. , McMahon Katherine D.
Published: August 2017

The metabolic activity of uncultivated microorganisms contributes to numerous ecosystem processes, ranging from nutrient cycling in the environment to influencing human health and disease. Advances in sequencing technology have enabled the assembly of genomes for these microorganisms, but our ability to generate reference genomes far outstrips our ability to analyze them. Common approaches to analyzing microbial metabolism require reconstructing the entirety of an organism’s metabolic pathways or performing targeted searches for genes involved in a specific process. This paper presents a third approach, in which draft metabolic reconstructions are used to identify compounds through which an organism may interact with its environment. These compounds can then guide more-intensive metabolic reconstruction efforts and can also provide new hypotheses about the specific contributions that microbes make to ecosystem-scale metabolic processes.
Educational attainment and differences in relative survival after acute myocardial infarction in Norway: a registry-based population study
Authors: Klitkou Søren Toksvig , Wangen Knut R
Published: August 2017

Background

Although there is a broad societal interest in socioeconomic differences in survival after an acute myocardial infarction, only a few studies have investigated how such differences relate to the survival in general population groups. We aimed to investigate education-specific survival after acute myocardial infarction and to compare this with the survival of corresponding groups in the general population.

Methods

Our study included the entire population of Norwegian patients admitted to hospitals for acute myocardial infarction during 2008–2010, with a 6- year follow-up period. Patient survival was measured relative to the expected survival in the general population for three educational groups: primary, secondary and tertiary. Education, sex, age and calendar year-specific expected survival were obtained from population life tables and adjusted for the presence of infarction-related mortality.

Results

Six-year patient survivals were 56.3% (55.3–57.2) and 65.5% (65.6–69.3) for the primary and tertiary educational groups (95% CIs), respectively. Also 6-year relative survival was markedly lower for the primary educational group: 70.2% (68.6–71.8) versus 81.2% (77.4–84.4). Throughout the follow-up period, patient survival tended to remain lower than the survival in the general population with the same educational background.

Conclusion

Both patient survival and relative survival after acute myocardial infarction are positively associated with educational level. Our findings may suggest that secondary prevention has been more effective for the highly educated.
Shifting tasks from pharmacy to non-pharmacy personnel for providing antiretroviral therapy to people living with HIV: a systematic review and meta-analysis
Authors: Mbeye Nyanyiwe Masingi , Adetokunboh Olatunji , Negussie Eyerusalem , Kredo Tamara , Wiysonge Charles Shey
Published: August 2017

Objectives

Lay people or non-pharmacy health workers with training could dispense antiretroviral therapy (ART) in resource-constrained countries, freeing up time for pharmacists to focus on more technical tasks. We assessed the effectiveness of such task-shifting in low-income and middle-income countries.

Method

We conducted comprehensive searches of peer-reviewed and grey literature. Two authors independently screened search outputs, selected controlled trials, extracted data and resolved discrepancies by consensus. We performed random-effects meta-analysis and assessed certainty of evidence using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach.

Results

Three studies with 1993 participants met the inclusion criteria, including two cluster trials conducted in Kenya and Uganda and an individually randomised trial conducted in Brazil. We found very low certainty evidence regarding mortality due to the low number of events. Therefore, we are uncertain whether there is a true increase in mortality as the effect size suggests, or a reduction in mortality between pharmacy and non-pharmacy models of dispensing ART (risk ratio (RR) 1.86, 95% CI 0.44 to 7.95, n=1993, three trials, very low certainty evidence). There may be no differences between pharmacy and non-pharmacy models of dispensing ART on virological failure (risk ratio (RR) 0.92, 95% CI 0.73 to 1.15, n=1993, three trials, low certainty evidence) and loss to follow-up (RR 1.13, 95% CI 0.68 to 1.91, n=1993. three trials, low certainty evidence). We found some evidence that costs may be reduced for the patient and health system when task-shifting is undertaken.

Conclusions

The low certainty regarding the evidence implies a high likelihood that further research may find the effects of the intervention to be substantially different from our findings. If resource-constrained countries decide to shift ART dispensing and distribution from pharmacy to non-pharmacy personnel, this should be accompanied by robust monitoring and impact evaluation.
Initial protocol for a national evaluation of an area-based intervention programme (A Better Start) on early-life outcomes: a longitudinal cohort study with comparison (control) cohort samples
Authors: Barlow Jane , Beake Sarah , Bick Debra , Bryson Caroline , Day Laurie , Gilby Nicholas , Glover Vivette , Knibbs Sarah , Leyland Alastair , Lindsay Geoff , Mathers Sandra , McKenna Katharine , Petrou Stavros , Purdon Susan , Sylva Kathy , Summerbell Carolyn D , Tudor Fiona , Wheeler Amy , Woolgar Virginia
Published: August 2017

Introduction

Pregnancy and the first few years of a child’s life are important windows of opportunity in which to equalise life chances. A Better Start (ABS) is an area-based intervention being delivered in five areas of socioeconomic disadvantage across England. This protocol describes an evaluation of the impact and cost-effectiveness of ABS.

Methods and analysis

The evaluation of ABS comprises a mixed-methods design including impact, cost-effectiveness and process components. It involves a cohort study in the 5 ABS areas and 15 matched comparison sites (n=2885), beginning in pregnancy in 2017 and ending in 2024 when the child is age 7, with a separate cross-sectional baseline survey in 2016/2017. Process data will include a profiling of the structure and services being provided in the five ABS sites at baseline and yearly thereafter, and data regarding the participating families and the services that they receive. Eligible participants will include pregnant women living within the designated sites, with recruitment beginning at 16 weeks of pregnancy. Data collection will involve interviewer-administered and self-completion surveys at eight time points. Primary outcomes include nutrition, socioemotional development, speech, language and learning. Data analysis will include the use of propensity score techniques to construct matched programme and comparison groups, and a range of statistical techniques to calculate the difference in differences between the intervention and comparison groups. The economic evaluation will involve a within-cohort study economic evaluation to compare individual-level costs and outcomes, and a decision analytic cost-effectiveness model to estimate the expected incremental cost per unit change in primary outcomes for ABS in comparison to usual care.

Ethics and dissemination

Ethical approval to conduct the study has been obtained. The learning and dissemination workstream involves working within and across the sites to generate learning via communities of practice and a range of learning and dissemination events.
Mortality and readmission following hip fracture surgery: a retrospective study comparing conventional and fast-track care
Authors: Haugan Kristin , Johnsen Lars G , Basso Trude , Foss Olav A
Published: August 2017

Objective

To compare the efficacies of two pathways—conventional and fast-track care—in patients with hip fracture.

Design

Retrospective single-centre study.

Setting

University hospital in middle Norway.

Participants

1820 patients aged ≥65 years with hip fracture (intracapsular, intertrochanteric or subtrochanteric).

Interventions

788 patients were treated according to conventional care from April 2008 to September 2011, and 1032 patients were treated according to fast-track care from October 2011 to December 2013.

Primary and secondary outcome

Primary: mortality and readmission to hospital, within 365 days follow-up. Secondary: length of stay.

Results

We found no statistically significant differences in mortality and readmission rate between patients in the fast-track and conventional care models within 365 days after the initial hospital admission. The conventional care group had a higher, no statistical significant mortality HR of 1.10 (95% CI 0.91 to 1.31, p=0.326) without and 1.16 (95% CI 0.96 to 1.40, p=0.118) with covariate adjustment. Regarding the readmission, the conventional care group sub-HR was 1.02 (95% CI 0.88 to 1.18, p=0.822) without and 0.97 (95% CI 0.83 to 1.12, p=0.644) with adjusting for covariates. Length of stay and time to surgery was statistically significant shorter for patients who received fast-track care, a mean difference of 3.4 days and 6 hours, respectively. There was no statistically significant difference in sex, type of fracture, age or Charlson Comorbidity Index score at baseline between patients in the two pathways.

Conclusions

There was insufficient evidence to show an impact of fast-track care on mortality and readmission. Length of stay and time to surgery were decreased.

Trial registration number

NCT00667914; results
Seroprevalence of hepatitis C virus infection in Cameroon: a systematic review and meta-analysis
Authors: Bigna Jean Joel , Amougou Marie A , Asangbeh Serra Lem , Kenne Angeladine Malaha , Nansseu Jobert Richie
Published: August 2017

Objective

Better knowledge of hepatitis C virus (HCV) seroprevalence at the national level can help to implement pertinent strategies to address the HCV-related burden. The aim of this paper was to estimate the seroprevalence of HCV infection in Cameroon.

Design

Systematic review and meta-analysis.

Participants

People residing in Cameroon.

Data sources

Electronic databases including PubMed/MEDLINE, AJOL, WHO-Afro Library, Africa Index Medicus, National Institute of Statistics and National AIDS Control Committee, Cameroon from 1 January 2000 to 15 December 2016 were searched. English and French languages papers were considered. Two independent investigators selected studies. The methodological quality of the studies was assessed using the Newcastle–Ottawa scale.

Results

31 studies including 36 407 individuals were finally considered. There was no national representative study. The overall pooled prevalence was 6.5% (95% CI 4.5% to 8.8%; I²=98.3%). A sensitivity analysis of individuals at low risk of HCV infection showed a pooled prevalence of 3.6% (95% CI 2.3% to 5.2%, I²=97.7%, 18 studies) among 22 860 individuals (general population, blood donors and pregnant women), which was higher than for a high-risk population (healthcare workers and people with other identified comorbidities), 12.2% (95% CI 4.9% to 22.2%; I²=98.3%, 13 studies); p=0.018. The prevalence was higher in the East region, in rural settings, and when using an enzyme immunoassay technique for detecting HCV antibodies. Sex, sites, study period, sample size, timing of data collection and methodological quality of studies were not sources of heterogeneity.

Limitation

One-third of studies (29.0%) had a low risk bias in their methodology and most were facility-based (87.1%).

Conclusion

The seroprevalence of HCV infection in Cameroon indicates the need for comprehensive and effective strategies to interrupt HCV transmission in the Cameroonian population. Specific attention is needed for the East region of the country, rural settings and high-risk populations. A national representative study is needed to provide better estimates.
Protocol for a randomised, double-masked, sham-controlled phase 4 study on the efficacy, safety and tolerability of intravitreal aflibercept monotherapy compared with aflibercept with adjunctive photodynamic therapy in polypoidal choroidal vasculopathy: the ATLANTIC study
Authors: Marques João Pedro , Farinha Cláudia , Costa Miguel Ângelo , Ferrão Ângela , Nunes Sandrina , Silva Rufino
Published: August 2017

Purpose

The purpose of this study is to compare the efficacy and safety of intravitreal aflibercept (IVA) with sham photodynamic therapy (sPDT) versus IVA with verteporfin PDT (vPDT) in a Caucasian population with treatment-naive polypoidal choroidal vasculopathy (PCV), enrolling into a treat and extend (T&E) regimen.

Methods and analysis

Randomised, double-masked, sham-controlled, multicentre phase 4 investigator-driven clinical trial. The primary outcomes are (1) change in best-corrected visual acuity (BCVA) from baseline and (2) polyp regression at week 52, assessed by indocyanine green angiography (ICGA). Fifty patients with treatment-naive PCV will be recruited from Portuguese and Spanish clinical sites. Eligible patients will receive monthly IVA for 3 months (week 0, week 4 and week 8). At week 16, all patients will repeat ICGA and undergo central randomisation (1:1 ratio) into one of the following groups: Group 1—IVA T&E + vPDT; Group 2—IVA T&E + sPDT. PDT will be performed at week 16, week 28 and week 40 in the presence of active polyps. After week 16, the presence of macular fluid on optical coherence tomography will determine the schedule of observations. When present, the interval between visits/injections will decrease 2 weeks (minimum 6 weeks). When not, the interval between visits/injections will increase 2 weeks (maximum 12 weeks). Efficacy will be evaluated based on BCVA, central retinal thickness and polyp regression. Safety parameters will include assessment of intraocular pressure, adverse events and serious adverse events.

Ethics and dissemination

This study was designed and shall be implemented and reported in accordance with the International Conference on Harmonisation (ICH) Harmonised Tripartite Guidelines for Good Clinical Practice, with applicable local regulations and with the ethical principles laid down in the Declaration of Helsinki. The study received approval from Comissão de Ética para a Investigação Clínica and Comité Ético de investigación Clínica del Hospital Universitari de Bellvitge.

Trial registration number

This study is registered under the EudraCT number: 2015-001368-20 and the ClinicalTrials.gov Identifier:NCT02495181.
Evaluating Maternity Units: a prospective cohort study of freestanding midwife-led primary maternity units in New Zealand—clinical outcomes
Authors: Grigg Celia P , Tracy Sally K , Tracy Mark , Daellenbach Rea , Kensington Mary , Monk Amy , Schmied Virginia
Published: August 2017

Objective

To compare maternal and neonatal birth outcomes and morbidities associated with the intention to give birth in a freestanding primary level midwife-led maternity unit (PMU) or tertiary level obstetric-led maternity hospital (TMH) in Canterbury, Aotearoa/New Zealand.

Design

Prospective cohort study.

Participants

407 women who intended to give birth in a PMU and 285 women who intended to give birth at the TMH in 2010–2011. All of the women planning a TMH birth were ‘low risk’, and 29 of the PMU cohort had identified risk factors.

Primary outcomes

Mode of birth, Apgar score of less than 7 at 5 min and neonatal unit admission. Secondary outcomes: labour onset, analgesia, blood loss, third stage of labour management, perineal trauma, non-pharmacological pain relief, neonatal resuscitation, breastfeeding, gestational age at birth, birth weight, severe morbidity and mortality.

Results

Women who planned a PMU birth were significantly more likely to have a spontaneous vaginal birth (77.9%vs62.3%, adjusted OR (AOR) 1.61, 95% CI 1.08 to 2.39), and significantly less likely to have an instrumental assisted vaginal birth (10.3%vs20.4%, AOR 0.59, 95% CI 0.37 to 0.93). The emergency and elective caesarean section rates were not significantly different (emergency: PMU 11.6% vs TMH 17.5%, AOR 0.88, 95% CI 0.55 to 1.40; elective: PMU 0.7% vs TMH 2.1%, AOR 0.34, 95% CI 0.08 to 1.41). There were no significant differences between the cohorts in rates of 5 min Apgar score of <7 (2.0%vs2.1%, AOR 0.82, 95% CI 0.27 to 2.52) and neonatal unit admission (5.9%vs4.9%, AOR 1.44, 95% CI 0.70 to 2.96). Planning to give birth in a primary unit was associated with similar or reduced odds of intrapartum interventions and similar odds of all measured neonatal well-being indicators.

Conclusions

The results of this study support freestanding midwife-led primary-level maternity units as physically safe places for well women to plan to give birth, with these women having higher rates of spontaneous vaginal births and lower rates of interventions and their associated morbidities than those who planned a tertiary hospital birth, with no differences in neonatal outcomes.
Prevalence, incidence and associated mortality of cardiovascular disease in patients with chronic kidney disease in low- and middle-income countries: a protocol for a systematic review and meta-analysis
Authors: Temgoua Mazou N , Danwang Celestin , Agbor Valirie Ndip , Noubiap Jean Jacques
Published: August 2017

Introduction

Chronic kidney disease (CKD) is a global public health problem, with cardiovascular disease (CVD) being the major cause of mortality in these patients. Despite a high burden of CKD among patients in low/middle-income countries (LMICs), evidence on the distribution of CVD among these patients is lacking. This review seeks to determine the prevalence, incidence and mortality risks of CVD in patients with CKD in LMICs.

Methods and analysis

A systematic search of Medline, Scopus, Embase, Cumulative Index of Nursing and Allied Health and WHO Global Health Library databases for published studies reporting on the prevalence, incidence and associated mortality risk of CVD in CKD patients in LMICs will be conducted from 1 May 1987 to 1 July 2017 with no language restriction. Two authors will independently screen, select studies, extract data and assess the risk of bias in each study. Clinically homogeneous studies will be pooled after assessing for clinical and statistical heterogeneity using the χ2test on Cochrane’s Q statistic which is quantified by I2values; assuming that I2values of 25%, 50% and 75% represent low, medium and high heterogeneity, respectively. Funnel-plot analysis and Egger’s test will be used to detect publication bias. Results will be presented according to WHO Regions (Africa, Americas, Eastern Mediterranean, Europe, South-East Asia and Western Pacific).

Ethics and dissemination

This proposed study will not require ethical approval as it will be based on published data. We will publish the final report of this review in a peer-reviewed journal, and the findings will be disseminated to the appropriate health authorities.
The effects of vitamin B12 supplementation in pregnancy and postpartum on growth and neurodevelopment in early childhood: Study Protocol for a Randomized Placebo Controlled Trial
Authors: Chandyo Ram K , Ulak Manjeswori , Kvestad Ingrid , Shrestha Merina , Ranjitkar Suman , Basnet Sudha , Hysing Mari , Shrestha Laxman , Strand Tor A
Published: August 2017

Introduction

Vitamin B12is crucial for normal cell division and differentiation, and necessary for the development and myelination of the central nervous system. Pregnant mothers in resource poor settings are at risk for poor vitamin B12status. Poor vitamin B12status in infancy is linked to poor growth and neurodevelopment. Brain development starts from conception, and pregnancy is a period of rapid growth and development for the brain.

Methods and analysis

The study is an individually randomised double-blind placebo controlled trial in 800 pregnant Nepalese women randomised in a 1:1 ratio. A daily dose of 50 µg of vitamin B12or placebo is given to women from early pregnancy, not later than week 15, until 6 months after birth. Weekly visits are conducted in order to record compliance, growth and morbidity. The primary outcomes are scores on the cognitive, language and motor subscales of the Bayley Scales of Infant and Toddler Development, Third Edition, measured at 6 and 12 months of age, and growth (length and weight) measured at 6 and 12 months of age.

Ethics and dissemination

National Health and Research Council, Nepal (NHRC 253/2016) and Regional Committee for Medical and Health Research Ethics of Western Norway (2016/1620/REK vest) have approved the study. Investigators who have contributed to the conceptualising, conducting, as well as being involved in the data analyses and manuscript writing will be eligible for authorship and be responsible to share outcomes with different stakeholders through publications and workshops. The results from this study may support new dietary guidelines for Nepalese and possibly South Asian pregnant women that can lead to improved pregnancy outcomes, neurodevelopment and cognitive functioning in children.

Trial registration number

Universal Trial Number: U1111-1183-4093. Trial registration: clinicaltrials.gov:NCT03071666. Protocol date: version 1.2, 1 June 2017.
Barriers and facilitators to the implementation of a community-based, multidisciplinary, family-focused childhood weight management programme in Ireland: a qualitative study
Authors: Kelleher Emily , Harrington Janas M , Shiely Frances , Perry Ivan J , McHugh Sheena M
Published: August 2017

Objective

To explore the barriers and facilitators experienced by those implementing a government-funded, community-based childhood weight management programme.

Design

Qualitative using semistructured interviews.

Setting

Two geographical regions in the south and west of Ireland.

Participants

29 national-level and local-level stakeholders responsible for implementing the programme, including professionals from dietetics, psychology, public health nursing, physiotherapy, health promotion and administration.

Methods

Framework analysis was used to identify barriers and facilitators, which were mapped onto six levels of factors influencing implementation outlined by Grol and Wensing: the innovation, the individual professional, the patient, the social context, the organisational context and the external environment.

Results

Most barriers occurred at the level of the organisational context. For all stakeholders, barriers arose due to the multidisciplinary nature of the programme, including the lack of role clarity and added complexity of working in different locations. Health professionals’ low-perceived self-efficacy in approaching the subject of weight with parents and parental resistance to hearing about their child’s weight status were barriers to programme implementation at the individual professional and patient levels, respectively. The main facilitators of implementation, occurring at the level of the health professional, included stakeholders’ recognition of the need for a weight management programme and personal interest in the area of childhood obesity. Having a local lead and supportive colleagues were further implementation drivers.

Conclusions

This study highlights the complexities associated with implementing a multidisciplinary childhood weight management programme, particularly translating such a programme to a community setting. Our results suggest the assignment of clear roles and responsibilities, the provision of sufficient practical training and resources, and organisational support play pivotal roles in overcoming barriers to change. This evidence can be used to develop an implementation plan to support the translation of interventions into real-world settings.
A qualitative study exploring the social and environmental context of recently acquired HIV infection among men who have sex with men in South-East England
Authors: Gourlay Annabelle , Fox Julie , Gafos Mitzy , Fidler Sarah , Nwokolo Nneka , Clarke Amanda , Gilson Richard , Orkin Chloe , Collins Simon , Porter Kholoud , Hart Graham
Published: August 2017

Objectives

A key UK public health priority is to reduce HIV incidence among gay and other men who have sex with men (MSM). This study aimed to explore the social and environmental context in which new HIV infections occurred among MSM in London and Brighton in 2015.

Design

A qualitative descriptive study, comprising in-depth interviews, was carried out as a substudy to the UK Register of HIV Seroconverters cohort: an observational cohort of individuals whose date of HIV seroconversion was well estimated. An inductive thematic analysis was conducted in NVivo, guided by a socio-ecological framework.

Setting

Participants were recruited from six HIV clinics in London and Brighton. Fieldwork was conducted between January and April 2015.

Participants

All MSM eligible for the UK Register Seroconverter cohort (an HIV-positive antibody test result within 12 months of their last documented HIV-negative test or other laboratory evidence of HIV seroconversion) diagnosed within the past 12 months and aged ≥18 were eligible for the qualitative substudy. 21 MSM participated, aged 22–61 years and predominantly white.

Results

A complex interplay of factors, operating at different levels, influenced risk behaviours and HIV acquisition. Participants saw risk as multi-factorial, but the relative importance of factors varied for each person. Individual psycho-social factors, including personal history, recent life stressors and mental health, enhanced vulnerability towards higher risk situations, while features of the social environment, such as chemsex and social media, and prevalent community beliefs regarding treatment and HIV normalisation, encouraged risk taking.

Conclusions

Recently acquired HIV infection among MSM reflects a complex web of factors operating at different levels. These findings point to the need for multi-level interventions to reduce the risk of HIV acquisition among high-risk MSM in the UK and similar settings.
Advanced chronic liver disease in the last year of life: a mixed methods study to understand how care in a specialist liver unit could be improved
Authors: Low Joseph , Davis Sarah , Vickerstaff Victoria , Greenslade Lynda , Hopkins Katherine , Langford Andrew , Marshall Aileen , Thorburn Douglas , Jones Louise
Published: August 2017

Objective

To identify the limitations in palliative care provision in the last year of life for people with liver cirrhosis and potential barriers to and enablers of palliative care.

Design

Mixed methods, including a retrospective case note review, qualitative focus groups and individual interviews.

Setting

A tertiary referral liver centre in the south of England (UK).

Participants

Purposively selected case notes of 30 people with cirrhosis who attended the tertiary referral liver centre and died during an 18-month period; a purposive sample of 22 liver health professionals who participated in either focus groups or individual interviews.

Primary and secondary outcomes

Data collected from case notes included hospital admissions, documented discussions of prognosis and palliative care provision. Qualitative methods explored management of people with cirrhosis, and barriers to and enablers of palliative care.

Results

Participants had high rates of hospital admissions and symptom burden. Clinicians rarely discussed prognosis or future care preferences; they lacked the skills and confidence to initiate discussions. Palliative care provision occurred late because clinicians were reluctant to refer due to their perception that reduced liver function is reversible, poor understanding of the potential of a palliative approach; palliative care was perceived negatively by patients and families.

Conclusions

People dying with cirrhosis have unpredictable trajectories, but share a common pathway of frequent admissions and worsening symptoms as death approaches. The use of clinical tools to identify the point of irreversible deterioration and joint working between liver services and palliative care may improve care for people with cirrhosis.
Psychometric evaluation of the Chinese version of the Person-centred Climate Questionnaire - Staff version (PCQ-S)
Authors: Cai Le , Ahlström Gerd , Tang Pingfen , Ma Ke , Edvardsson David , Behm Lina , Fu Haiyan , Zhang Jie , Yang Jiqun
Published: August 2017

Objectives

The aim of the study was to evaluate the psychometric properties of a Chinese translation of the English version of the Person-centred Climate Questionnaire – Staff version (PCQ-S) for Chinese palliative care staff in a hospital context.

Design

This was a cross-sectional design. The 14-item English PCQ-S was translated and backtranslated using established procedures. Construct validity and reliability including internal consistency and test-retest reliability were assessed among hospital staff. Construct validity was tested using principal component analysis (PCA), internal consistency was assessed using Cronbach’s alpha, and test-retest reliability was evaluated with the weighted kappa (Kp), Pearson correlation coefficient (r) and intra-class correlation coefficient (ICC).

Setting

This study was conducted in three hospitals in Kunming, the capital of Yunnan province in south-west China.

Participants

A sample of hospital staff (n=163) on duty in the palliative care departments of three hospitals in Kunming consented to participate in the study.

Results

The 14-item Chinese PCQ-S consists of the three subscales also present in other language versions. It showed strong internal consistency, with a Cronbach’s alpha of 0.94 for the total scale, 0.87 for the safety subscale, 0.90 for the everydayness subscale and 0.88 for the community subscale. The Chinese PCQ-S had high test-retest reliability as evidenced by a high Kp coefficient and a high correlation coefficient for all scales between test and retest scores, on ‘a climate of safety’ (Kp=0.77, r=0.88, p<0.01), ‘a climate of everydayness’ (Kp=0.82, r=0.91, p<0.01), ‘a climate of community’ (Kp=0.75, r=0.79, p<0.01), and on overall scale scores (Kp=0.85, r=0.93, p<0.01). The ICC to evaluate the test-retest reliability was 0.97 (95% CI 0.95 to 0.98).

Conclusions

The Chinese version of the PCQ-S showed satisfactory reliability and validity for assessing staff perceptions of person-centred care in Chinese hospital environments.
Study protocol for a multi-institutional, randomised, double-blinded, placebo-controlled phase III trial investigating additive efficacy of duloxetine for neuropathic cancer pain refractory to opioids and gabapentinoids: the DIRECT study
Authors: Matsuoka Hiromichi , Ishiki Hiroto , Iwase Satoru , Koyama Atsuko , Kawaguchi Takashi , Kizawa Yoshiyuki , Morita Tatsuya , Matsuda Yoshinobu , Miyaji Tempei , Ariyoshi Keisuke , Yamaguchi Takuhiro
Published: August 2017

Introduction

Management of patients with cancer suffering from neuropathic pain refractory to opioids and gabapentinoids remains an important challenge. Duloxetine is one of the choices after first-line treatment fails. The efficacy of duloxetine has been reported in patients with non-cancer disease and in chemotherapy-induced peripheral neuropathy, but no randomised clinical trials have examined its effects on neuropathic cancer pain refractory to first-line treatment. The objective of this study is to assess the analgesic efficacy of duloxetine in patients suffering from neuropathic cancer pain refractory to opioids and gabapentinoids.

Methods and analysis

A multi-institutional, prospective, randomised, double-blind, placebo-controlled, two-parallel trial is planned. The inclusion criteria are adult patients with cancer suffering from neuropathic cancer pain refractory to opioids and gabapentinoids, patients with a Numerical Rating Scale (NRS) pain score of 4 or higher and patients with a total Hospital Anxiety and Depression Scale score of less than 20. Patients with chemotherapy-induced peripheral neuropathy are excluded. The study will take place at 14 sites across Japan. Participants will be randomised (1:1 allocation ratio) to a duloxetine intervention group or a placebo control group. Evaluations will be made at baseline (T0 randomisation), day 0 (T1), day 3 (T2) and day 10 (T3). The primary endpoint is defined as the difference in NRS score for pain intensity (average over the previous 24 hours) at T3 between the duloxetine and placebo groups. A sample size of 70 patients will be examined between July 2015 and March 2018.

Ethics and dissemination

Ethics approval was obtained at all participating sites.

The results of this study will be submitted for publication in international peer-reviewed journals and the key findings presented at international scientific conferences.

Trial registration number

UMIN000017647; Pre-results.

Protocol version

2.2, 26 April 2017.