Breaking Up (Amyloid) Is Hard to Do

Gandy and Heppner discuss the implications of a new animal study on our understanding of the pathogenesis and treatment of Alzheimer disease

Healthcare staff's experience in providing end-of-life care to children: A mixed-method review.

BACKGROUND: Staff who provide end-of-life care to children not only have to deal with their own sense of loss but also that of bereaved families. There is a dearth of knowledge on how they cope with these challenges. AIM: The aim of this review is to explore the experiences of healthcare professionals who provide end-of-life care to children in order to inform the development of interventions to support them, thereby improving the quality of paediatric care for both children and their families. DATA SOURCES: Searches included CINAHL, MEDLINE, Web of Science, EMBASE, PsychINFO and The Cochrane Library in June 2015, with no date restrictions. Additional literature was uncovered from searching reference lists of relevant studies, along with contacting experts in the field of paediatric palliative care. DESIGN: This was a systematic mixed studies review. Study selection, appraisal and data extraction were conducted by two independent researchers. Integrative thematic analysis was used to synthesise the data. RESULTS: The 16 qualitative, 6 quantitative and 8 mixed-method studies identified included healthcare professionals in a range of settings. Key themes identified rewards and challenges of providing end-of-life care to children, the impact on staff's personal and professional lives, coping strategies and key approaches to help support staff in their role. CONCLUSION: Education focusing on the unique challenges of providing end-of-life care to children and the importance of self-care, along with timely multidisciplinary debriefing, are key strategies for improving healthcare staff's experiences, and as such the quality of care they provide

Behavioral Impairment and Oxidative Damage Induced by Chronic Application of Nonylphenol

Nonylphenol (NP) is a degradation product of nonylphenol polyethoxylates, which are widely used in the production of industrial and consumer surfactants. The aim of the present study was to evaluate the effect of NP on the antioxidant capacity and cognitive ability of mice. NP was given orally by gavages at doses of 0, 50, 100, and 200 mg kg−1 d−1 for 90 days. The results showed that NP significantly decreased the activity of superoxide dismutases (SOD), catalase (CAT), glutathione peroxidase (GPx), and glutathione reductase (GR) and at the same time increased malondialdehyde (MDA) levels in mice brains. Exploration, memory function and ability to learn a novel task were significantly decreased in NP fed mice. These results indicate that chronic high dose of NP exposure has the potential to generate oxidative stress and induce the cognitive impairment in male mice

Differential Production Cross Section of Z Bosons as a Function of Transverse Momentum at sqrt{s}=1.8 TeV

We present a measurement of the transverse momentum distribution of Z bosons produced in ppbar collisions at sqrt{s}=1.8 TeV using data collected by the D0 experiment at the Fermilab Tevatron Collider during 1994--1996. We find good agreement between our data and a current resummation calculation. We also use our data to extract values of the non-perturbative parameters for a particular version of the resummation formalism, obtaining significantly more precise values than previous determinations.Comment: 10 pages, 2 figures, submitted to Phys. Rev. Letters v2 has margin error correcte

Lacosamide adjunctive therapy for partial-onset seizures: a meta-analysis

Background. The relative efficacy and safety of lacosamide as adjunctive therapy compared to other antiepileptic drugs has not been well established.Objective. To determine if lacosamide provides improved efficacy and safety, reduced length of hospital stay and improved quality of life compared with other anti-epileptic therapies for adults with partial-onset seizures.Data Sources. A systematic review of the medical literature using Medline (1946–Week 4, 2012), EMBASE (1980–Week 3, 2012), Cochrane Central Register of Controlled Trials (Issue 1 of 12, January 2012). Additional studies were identified (through to February 7, 2012) by searching bibliographies, the FDA drug approval files, clinical trial registries and major national and international neurology meeting abstracts. No restrictions on publication status or language were applied.Study Selection. Randomized controlled trials of lacosamide in adults with partial-onset seizures were included.Data Extraction. Study selection, extraction and risk of bias assessment were performed independently by two authors. Authors of studies were contacted for missing data.Data Synthesis. All pooled analyses used the random effects model.Results. Three trials (1311 patients) met inclusion criteria. Lacosamide increased the 50% responder rate compared to placebo (RR 1.68 [95% CI 1.36 to 2.08]; I2 = 0%). Discontinuation due to adverse events was statistically significantly higher in the lacosamide arm (RR3.13 [95% CI 1.94 to 5.06]; I2 = 0%). Individual adverse events (ataxia, dizziness, fatigue, and nausea) were also significantly higher in the lacosamide group.Limitations. All dosage arms from the included studies were pooled to make a single pair-wise comparison to placebo. Selective reporting of outcomes was found in all of the included RCTs.Conclusions. Lacosamide as adjunctive therapy in patients with partial-onset seizures increases the 50% responder rate but with significantly more adverse events compared to the placebo

Physiotherapy interventions for people with dementia and a hip fracture-a scoping review of the literature.

BACKGROUND: People with dementia are 2.7 times more likely to suffer a hip fracture than those without and their management is estimated to cost £0.92 billion per year. Yet there has been little focus on the effectiveness of interventions for this population. OBJECTIVE: The aim of this scoping review was to summarise the current available evidence for physiotherapy interventions for people with dementia who fracture their hip as well as to identify gaps in the literature that may require further research. DATA SOURCES: A systematic search of the following databases was undertaken-TRIP, CINAHL, Amed, Embase, PEDro, PsycINFO, Cochrane Library, Open Grey, Ethos, ISRCTN, Proquest, PROSPERO and UK Clinical Trials Gateway. STUDY SELECTION: Articles were included if they described an intervention which is considered within the scope of a physiotherapist and targeted those with both a hip fracture and dementia. SYNTHESIS METHODS: A narrative summary was then undertaken to describe the current state of the literature. RESULTS: Twenty six studies were included, of which thirteen were observational, six RCTs, two qualitative, two surveys and three systematic reviews. Only nine studies focused explicitly on physiotherapy interventions. CONCLUSION: The findings of this scoping review suggest there is limited evidence to guide physiotherapists in the management of people with dementia who fracture their hip. No evidence was found about perceptions or experiences of patients in this group or of the physiotherapists involved in their care. Further research is needed to develop and evaluate physiotherapy interventions for people with dementia who fracture their hip

IT-adoption and the interaction of task, technology and individuals: a fit framework and a case study

BACKGROUND: Factors of IT adoption have largely been discussed in the literature. However, existing frameworks (such as TAM or TTF) are failing to include one important aspect, the interaction between user and task. METHOD: Based on a literature study and a case study, we developed the FITT framework to help analyse the socio-organisational-technical factors that influence IT adoption in a health care setting. RESULTS: Our FITT framework ("Fit between Individuals, Task and Technology") is based on the idea that IT adoption in a clinical environment depends on the fit between the attributes of the individual users (e.g. computer anxiety, motivation), attributes of the technology (e.g. usability, functionality, performance), and attributes of the clinical tasks and processes (e.g. organisation, task complexity). We used this framework in the retrospective analysis of a three-year case study, describing the adoption of a nursing documentation system in various departments in a German University Hospital. We will show how the FITT framework helped analyzing the process of IT adoption during an IT implementation: we were able to describe every found IT adoption problem with regard to the three fit dimensions, and any intervention on the fit can be described with regard to the three objects of the FITT framework (individual, task, technology). We also derive facilitators and barriers to IT adoption of clinical information systems. CONCLUSION: This work should support a better understanding of the reasons for IT adoption failures and therefore enable better prepared and more successful IT introduction projects. We will discuss, however, that from a more epistemological point of view, it may be difficult or even impossible to analyse the complex and interacting factors that predict success or failure of IT projects in a socio-technical environment

Ethics review as a component of institutional approval for a multicentre continuous quality improvement project: the investigator's perspective

BACKGROUND: For ethical approval of a multicentre study in Canada, investigators must apply separately to individual Research Ethics Boards (REBs). In principle, the protection of human research subjects is of utmost importance. However, in practice, the process of multicentre ethics review can be time consuming and costly, requiring duplication of effort for researchers and REBs. We used our experience with ethical review of The Canadian Perinatal Network (CPN), to gain insight into the Canadian system. METHODS: The applications forms of 16 different REBs were abstracted for a list of standardized items. The application process across sites was compared. Correspondence between the REB and the investigators was documented in order to construct a timeline to approval, identify the specific issues raised by each board, and describe how they were resolved. RESULTS: Each REB had a different application form. Most (n = 9) had a two or three step application process. Overall, it took a median of 31 days (range 2-174 days) to receive an initial response from the REB. Approval took a median of 42 days (range 4-443 days). Privacy and consent were the two major issues raised. Several additional minor or administrative issues were raised which delayed approval. CONCLUSIONS: For CPN, the Canadian REB process of ethical review proved challenging. REBs acted independently and without unified application forms or submission procedures. We call for a critical examination of the ethical, privacy and institutional review processes in Canada, to determine the best way to undertake multicentre review

Selective AKR1C3 inhibitors do not recapitulate the anti-leukaemic activities of the pan-AKR1C inhibitor medroxyprogesterone acetate

Background: We and others have identified the aldo-keto reductase AKR1C3 as a potential drug target in prostate cancer, breast cancer and leukaemia. As a consequence, significant effort is being invested in the development of AKR1C3-selective inhibitors. Methods: We report the screening of an in-house drug library to identify known drugs that selectively inhibit AKR1C3 over the closely related isoforms AKR1C1, 1C2 and 1C4. This screen initially identified tetracycline as a potential AKR1C3-selective inhibitor. However, mass spectrometry and nuclear magnetic resonance studies identified that the active agent was a novel breakdown product (4-methyl(de-dimethylamine)-tetracycline (4-MDDT)). Results: We demonstrate that, although 4-MDDT enters AML cells and inhibits their AKR1C3 activity, it does not recapitulate the anti-leukaemic actions of the pan-AKR1C inhibitor medroxyprogesterone acetate (MPA). Screens of the NCI diversity set and an independently curated small-molecule library identified several additional AKR1C3-selective inhibitors, none of which had the expected anti-leukaemic activity. However, a pan AKR1C, also identified in the NCI diversity set faithfully recapitulated the actions of MPA. Conclusions: In summary, we have identified a novel tetracycline-derived product that provides an excellent lead structure with proven drug-like qualities for the development of AKR1C3 inhibitors. However, our findings suggest that, at least in leukaemia, selective inhibition of AKR1C3 is insufficient to elicit an anticancer effect and that multiple AKR1C inhibition may be required