Clinical and testing protocols for the analysis of epidermal growth factor receptor mutations in East Asian patients with non-small cell lung cancer:a combined clinical-molecular pathological approach

Several randomized phase III studies in advanced stage non-small cell lung cancer (NSCLC) confirmed the superior response rate and progression-free survival of using epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor as first-line therapy compared with chemotherapy in patients with activating EGFR mutations. Despite the need for EGFR mutation tests to guide first-line therapy in East Asian NSCLC, there are no current standard clinical and testing protocols.

Use of weaning protocols for reducing duration of mechanical ventilation in critically ill adult patients: Cochrane systematic review and meta-analysis.

Objective To investigate the effects of weaning protocols on the total duration of mechanical ventilation, mortality, adverse events, quality of life, weaning duration, and length of stay in the intensive care unit and hospital.

Design Systematic review.

Data sources Cochrane Central Register of Controlled Trials, Medline, Embase, CINAHL, LILACS, ISI Web of Science, ISI Conference Proceedings, Cambridge Scientific Abstracts, and reference lists of articles. We did not apply language restrictions.

Review methods We included randomised and quasi-randomised controlled trials of weaning from mechanical ventilation with and without protocols in critically ill adults.

Data selection Three authors independently assessed trial quality and extracted data. A priori subgroup and sensitivity analyses were performed. We contacted study authors for additional information.

Results Eleven trials that included 1971 patients met the inclusion criteria. Compared with usual care, the geometric mean duration of mechanical ventilation in the weaning protocol group was reduced by 25% (95% confidence interval 9% to 39%, P=0.006; 10 trials); the duration of weaning was reduced by 78% (31% to 93%, P=0.009; six trials); and stay in the intensive care unit length by 10% (2% to 19%, P=0.02; eight trials). There was significant heterogeneity among studies for total duration of mechanical ventilation (I(2)=76%, P

Conclusion There is evidence of a reduction in the duration of mechanical ventilation, weaning, and stay in the intensive care unit when standardised weaning protocols are used, but there is significant heterogeneity among studies and an insufficient number of studies to investigate the source of this heterogeneity. Some studies suggest that organisational context could influence outcomes, but this could not be evaluated as it was outside the scope of this review.

Performance analysis of switch-and-stay combining in two-way relay systems with analog network coding and time-division broadcast protocols

In this paper, weconsider switch-and-stay combining (SSC) in two-way relay systems with two amplify-and-forward relays, one of which is activated to assist the information exchange between the two sources. The system operates in either analog network coding (ANC) protocol where the communication is only achieved with the help of the active relay or timedivision broadcast (TDBC) protocol where the direct link between two sources can be utilized to exploit more diversity gain. In both cases, we study the outage probability and bit error rate (BER) for Rayleigh fading channels. In particular, we derive closed-form lower bounds for the outage probability and the average BER, which remain tight for different fading conditions. We also present asymptotic analysis for both the outage probability and the average BER at high signalto-noise ratio. It is shown that SSC can achieve the full diversity order in two-way relay systems for both ANC and TDBC protocols with proper switching thresholds. Copyright © 2014 John Wiley & Sons, Ltd.

Preferred reporting items for systematic review and meta-analysis protocols (PRISMA-P) 2015: elaboration and explanation

Protocols of systematic reviews and meta-analyses allow for planning and documentation of review methods, act as a guard against arbitrary decision making during review conduct, enable readers to assess for the presence of selective reporting against completed reviews, and, when made publicly available, reduce duplication of efforts and potentially prompt collaboration. Evidence documenting the existence of selective reporting and excessive duplication of reviews on the same or similar topics is accumulating and many calls have been made in support of the documentation and public availability of review protocols. Several efforts have emerged in recent years to rectify these problems, including development of an international register for prospective reviews (PROSPERO) and launch of the first open access journal dedicated to the exclusive publication of systematic review products, including protocols (BioMed Central's Systematic Reviews). Furthering these efforts and building on the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-analyses) guidelines, an international group of experts has created a guideline to improve the transparency, accuracy, completeness, and frequency of documented systematic review and meta-analysis protocols--PRISMA-P (for protocols) 2015. The PRISMA-P checklist contains 17 items considered to be essential and minimum components of a systematic review or meta-analysis protocol.This PRISMA-P 2015 Explanation and Elaboration paper provides readers with a full understanding of and evidence about the necessity of each item as well as a model example from an existing published protocol. This paper should be read together with the PRISMA-P 2015 statement. Systematic review authors and assessors are strongly encouraged to make use of PRISMA-P when drafting and appraising review protocols.

Preferred reporting items for systematic review and meta-analysis protocols (PRISMA-P) 2015 statement

Systematic reviews should build on a protocol that describes the rationale, hypothesis, and planned methods of the review; few reviews report whether a protocol exists. Detailed, well-described protocols can facilitate the understanding and appraisal of the review methods, as well as the detection of modifications to methods and selective reporting in completed reviews. We describe the development of a reporting guideline, the Preferred Reporting Items for Systematic reviews and Meta-Analyses for Protocols 2015 (PRISMA-P 2015). PRISMA-P consists of a 17-item checklist intended to facilitate the preparation and reporting of a robust protocol for the systematic review. Funders and those commissioning reviews might consider mandating the use of the checklist to facilitate the submission of relevant protocol information in funding applications. Similarly, peer reviewers and editors can use the guidance to gauge the completeness and transparency of a systematic review protocol submitted for publication in a journal or other medium.

Factors that impact on the use of mechanical ventilation weaning protocols in critically ill adults and children: a qualitative-evidence synthesis

Background:
Prolonged mechanical ventilation is associated with a longer intensive care unit (ICU) length of stay and higher mortality. Consequently, methods to improve ventilator weaning processes have been sought. Two recent Cochrane systematic reviews in ICU adult and paediatric populations concluded that protocols can be effective in reducing the duration of mechanical ventilation, but there was significant heterogeneity in study findings. Growing awareness of the benefits of understanding the contextual factors impacting on effectiveness has encouraged the integration of qualitative evidence syntheses with effectiveness reviews, which has delivered important insights into the reasons underpinning (differential) effectiveness of healthcare interventions.

Objectives:
1. To locate, appraise and synthesize qualitative evidence concerning the barriers and facilitators of the use of protocols for weaning critically-ill adults and children from mechanical ventilation;

2. To integrate this synthesis with two Cochrane effectiveness reviews of protocolized weaning to help explain observed heterogeneity by identifying contextual factors that impact on the use of protocols for weaning critically-ill adults and children from mechanical ventilation;

3. To use the integrated body of evidence to suggest the circumstances in which weaning protocols are most likely to be used.

Search methods:
We used a range of search terms identified with the help of the SPICE (Setting, Perspective, Intervention, Comparison, Evaluation) mnemonic. Where available, we used appropriate methodological filters for specific databases. We searched the following databases: Ovid MEDLINE, Embase, OVID, PsycINFO, CINAHL Plus, EBSCOHost, Web of Science Core Collection, ASSIA, IBSS, Sociological Abstracts, ProQuest and LILACS on the 26th February 2015. In addition, we searched: the grey literature; the websites of professional associations for relevant publications; and the reference lists of all publications reviewed. We also contacted authors of the trials included in the effectiveness reviews as well as of studies (potentially) included in the qualitative synthesis, conducted citation searches of the publications reporting these studies, and contacted content experts.

We reran the search on 3rd July 2016 and found three studies, which are awaiting classification.

Selection criteria:
We included qualitative studies that described: the circumstances in which protocols are designed, implemented or used, or both, and the views and experiences of healthcare professionals either involved in the design, implementation or use of weaning protocols or involved in the weaning of critically-ill adults and children from mechanical ventilation not using protocols. We included studies that: reflected on any aspect of the use of protocols, explored contextual factors relevant to the development, implementation or use of weaning protocols, and reported contextual phenomena and outcomes identified as relevant to the effectiveness of protocolized weaning from mechanical ventilation.

Data collection and analysis:
At each stage, two review authors undertook designated tasks, with the results shared amongst the wider team for discussion and final development. We independently reviewed all retrieved titles, abstracts and full papers for inclusion, and independently extracted selected data from included studies. We used the findings of the included studies to develop a new set of analytic themes focused on the barriers and facilitators to the use of protocols, and further refined them to produce a set of summary statements. We used the Confidence in the Evidence from Reviews of Qualitative Research (CERQual) framework to arrive at a final assessment of the overall confidence of the evidence used in the synthesis. We included all studies but undertook two sensitivity analyses to determine how the removal of certain bodies of evidence impacted on the content and confidence of the synthesis. We deployed a logic model to integrate the findings of the qualitative evidence synthesis with those of the Cochrane effectiveness reviews.

Main results:
We included 11 studies in our synthesis, involving 267 participants (one study did not report the number of participants). Five more studies are awaiting classification and will be dealt with when we update the review.

The quality of the evidence was mixed; of the 35 summary statements, we assessed 17 as ‘low’, 13 as ‘moderate’ and five as ‘high’ confidence. Our synthesis produced nine analytical themes, which report potential barriers and facilitators to the use of protocols. The themes are: the need for continual staff training and development; clinical experience as this promotes felt and perceived competence and confidence to wean; the vulnerability of weaning to disparate interprofessional working; an understanding of protocols as militating against a necessary proactivity in clinical practice; perceived nursing scope of practice and professional risk; ICU structure and processes of care; the ability of protocols to act as a prompt for shared care and consistency in weaning practice; maximizing the use of protocols through visibility and ease of implementation; and the ability of protocols to act as a framework for communication with parents.

Authors' conclusions:
There is a clear need for weaning protocols to take account of the social and cultural environment in which they are to be implemented. Irrespective of its inherent strengths, a protocol will not be used if it does not accommodate these complexities. In terms of protocol development, comprehensive interprofessional input will help to ensure broad-based understanding and a sense of ‘ownership’. In terms of implementation, all relevant ICU staff will benefit from general weaning as well as protocol-specific training; not only will this help secure a relevant clinical knowledge base and operational understanding, but will also demonstrate to others that this knowledge and understanding is in place. In order to maximize relevance and acceptability, protocols should be designed with the patient profile and requirements of the target ICU in mind. Predictably, an under-resourced ICU will impact adversely on protocol implementation, as staff will prioritize management of acutely deteriorating and critically-ill patients.

Relocation, reproduction and remaining alive in the orb-web spider

When mortality is high, animals run a risk if they wait to accumulate resources for improved reproduction so they may trade-off the time of reproduction with number and size of offspring. Animals may attempt to improve food acquisition by relocation, even in 'sit and wait' predators. We examine these factors in an isolated population of an orb-web spider Zygiella x-notata. The population was monitored for 200 days from first egg laying until all adults had died. Large females produced their first clutch earlier than did small females and there was a positive correlation between female size and the number and size of eggs produced. Many females, presumably without eggs, abandoned their web site and relocated their web position. This is presumed because female Zygiella typically guard their eggs. In total, c. 25% of females reproduced but those that relocated were less likely to do so, and if they did, they produced the clutch at a later date than those that remained. When the date of lay was controlled there was no effect of relocation on egg number but relocated females produced smaller eggs. The data are consistent with the idea that females in resource-poor sites are more likely to relocate. Relocation seems to be a gamble to find a more productive site but one that achieves only a late clutch of small eggs and few achieve that.

Endodontic 'solutions' part 1:A literature review on the use of endodontic lubricants, irrigants and medicaments

Endodontic lubricants, irrigants and medicaments help prepare and disinfect root canal systems (RCS) but primary and secondary cases involve different microbes and therefore it is unlikely that one protocol will be effective for both case types. Each individual 'solution' or sequence of 'solutions' could play a significant role in each case type, but there are no detailed published guidelines in existence. To help inform clinical practice it was decided to undertake a literature review followed by a UK and Republic of Ireland wide audit on current endodontic 'solution' usage within dental schools. The literature review was undertaken under the following headings: pre-op oral rinse; file lubricants; root canal irrigants and intracanal medicaments and provides an evidence base for protocol development for both primary and retreatment cases. The audit project and the protocols developed from the findings of both the literature review and audit will be presented in Part 2.

Understanding informal kinship care: a critical narrative review of theory and research

Many children are cared for on a full-time basis by relatives or adult friends, rather than their biological parents, and often in response to family crises. These kinship care arrangements have received increasing attention from the social science academy and social care professions. However, more information is needed on informal kinship care that is undertaken without official ratification by welfare agencies and often unsupported by the state. This article presents a comprehensive, narrative review of international, research literature on informal, kinship care to address this gap. Using systematic search and review protocols, it synthesises findings regarding: (i) the way that informal kinship care is defined and conceptualised; (ii) the needs of the carers and children; and (iii) ways of supporting this type of care. A number of prominent themes are highlighted including the lack of definitional clarity; the various adversities experienced by the families; and the requirement to understand the interface between formal and informal supports. Key messages are finally identified to inform the development of family friendly policies, interventions, and future research.

DNA methylation profiling in cell models of diabetic nephropathy

We have previously identified differentially expressed genes in cell models of diabetic nephropathy and renal biopsies. Here we have performed quantitative DNA methylation profiling in cell models of diabetic nephropathy. Over 3,000 CpG units in the promoter regions of 192 candidate genes were assessed in unstimulated human mesangial cells (HMCs) and proximal tubular epithelial cells (PTCs) compared to HMCs or PTCs exposed to appropriate stimuli. A total of 301 CpG units across 38 genes (similar to 20%) were identified as differentially methylated in unstimulated HMCs versus PTCs. Analysis of amplicon methylation values in unstimulated versus stimulated cell models failed to demonstrate a >20% difference between amplicons. In conclusion, our results demonstrate that specific DNA methylation signatures are present in HMCs and PTCs, and standard protocols for exposure of renal cells to stimuli that alter gene expression may be insufficient to replicate possible alterations in DNA methylation profiles in diabetic nephropathy.

On the Problems of Mixing RCTs with Qualitative Research: The Case of the MRC Framework for the Evaluation of Complex Healthcare Interventions

In the perceived hierarchy of research designs, the results from randomized controlled trials are considered to provide the highest level of evidence. Indeed these trials have been upheld as the gold standard in research. The benefits and limitations of the randomized controlled trial as a method of evaluating the effectiveness of healthcare interventions are presented. The article then examines the different levels of complexity within healthcare interventions and the problems this poses in determining effectiveness. In an effort to provide a solution to this problem, the Medical Research Council produced a framework to assist investigators to develop and evaluate complex healthcare interventions. The framework is described with reference to an example of implementing and evaluating protocols for weaning patients in the intensive care unit. The framework is critiqued on the basis that it involves an ambiguous or contradictory ontology, which fails to articulate the relationship between the positivism of randomized controlled trials with the relativism of qualitative approaches. It is concluded that the use of realist strategies in combination with randomized controlled trials provides the most coherent solution to this quandary

Direct Quantification of Inorganic Polyphosphate in Microbial Cells Using 4 '-6-Diamidino-2-Phenylindole (DAPI)

Inorganic polyphosphate (polyP) is increasingly being recognized as an important phosphorus sink within the environment, playing a central role in phosphorus exchange and phosphogenesis. Yet despite the significant advances made in polyP research there is a lack of rapid and efficient analytical approaches for the quantification of polyP accumulation in microbial cultures and environmental samples. A major drawback is the need to extract polyP from cells prior to analysis. Due to extraction inefficiencies this can lead to an underestimation of both intracellular polyP levels and its environmental pool size: we observed 23-58% loss of polyP using standard solutions and current protocols. Here we report a direct fluorescence based DAPI assay system which removes the requirement for prior polyP extraction before quantification. This increased the efficiency of polyP detection by 28-55% in microbial cultures suggesting quantitative measurement of the intracellular polyP pool. It provides a direct polyP assay which combines quantification capability with technical simplicity. This is an important step forward in our ability to explore the role of polyP in cellular biology and biogeochemical nutrient cycling.

Motor skill deficits in children with partial hearing

AIM:
We examined the effect of partial hearing, including cochlear implantation, on the development of motor skills in children (aged 6-12y).

METHOD:
Three independent groups of children were selected: a partial hearing group (n=25 [14 males, 11 females]; mean age 8y 8mo, SD 1y 10mo), a nonverbal IQ-matched group (n=27 [15 males, 12 females]; mean age 9y, SD 1y 6mo), and an age-matched group (n=26 [8 males, 18 females]; mean age 8y 8mo, SD 1y 7mo) from three schools with special units for children with partial hearing. All children with partial hearing had a bilateral hearing loss >60 decibels. Motor and balance skills were assessed using the Movement Assessment Battery for Children (MABC) and two protocols from the NeuroCom Balance Master clinical procedures.

RESULTS:
The mean standardized total MABC score of the children with partial hearing (95% confidence interval [CI] 71.8-88.7) was significantly lower than both the age-matched (95% CI 95.8-111.4; p<0.01) and the IQ-matched (95% CI 87.6-103.0; p=0.03) comparison groups. The children with partial hearing had particular difficulties with balance, most notably during tests of intersensory demand. However, subgroup analyses revealed that the effect of cochlear implantation was clearly dependent on the nature of the task.

INTERPRETATION:
Children with partial hearing are at high risk of clinical levels of motor deficit, with balance difficulties providing support for conventional vestibular deficit theory. However, the effect of cochlear implantation suggests that other sensory systems may be involved. A broader ecological perspective, which takes into account factors external to the child, may prove a useful framework for future research.