Observation of Monoenergetic Electrons from Two-Pulse Ionization Injection in Quasilinear Laser Wakefields.

The generation of low emittance electron beams from laser-driven wakefields is crucial for the development of compact x-ray sources. Here, we show new results for the injection and acceleration of quasimonoenergetic electron beams in low amplitude wakefields experimentally and using simulations. This is achieved by using two laser pulses decoupling the wakefield generation from the electron trapping via ionization injection. The injection duration, which affects the beam charge and energy spread, is found to be tunable by adjusting the relative pulse delay. By changing the polarization of the injector pulse, reducing the ionization volume, the electron spectra of the accelerated electron bunches are improved.

Aetiology and clinical features of dysentery in children aged <5 years in rural Bangladesh.

The study identified the common aetiological agents and prominent clinical features of dysentery cases in children aged <5 years and compared this to non-dysentery diarrhoeal cases from the same population. From January 2010 to December 2011, 2324 children aged <5 years received treatment at Kumudini Hospital, of which 682 (29%) presented with dysentery. Of the dysenteric children, aetiology could not be determined for over half (61%). Shigella spp. accounted for 32% of dysentery cases. Significant associations were found between presence of blood in stool and: child age (24-59 months) [odds ratio (OR) 2.21, 95% confidence interval (CI) 1.49-3.27], no treatment of drinking water at home (OR 2.00, 95% CI 1.09-3.67), vomiting (OR 0.19, 95% CI 0.14-0.25), abdominal pain (OR 4.68, 95% CI 3.24-6.77), straining (OR 16.45, 95% CI 11.92-22.69), wasting (OR 1.66, 95% CI 1.15-2.41), and presence of Shigella in stool (OR 6.25, 95% CI 4.20-9.29) after controlling for confounders. This study makes it clear that appropriate public health strategies are needed to reduce the burden of dysentery in Bangladesh.

Geographical diversity in seasonality of major diarrhoeal pathogens in Bangladesh observed between 2010 and 2012.

The study aimed to determine the geographical diversity in seasonality of major diarrhoeal pathogens among 21 138 patients enrolled between 2010 and 2012 in two urban and two rural sites in Bangladesh under the surveillance system of the International Centre for Diarrhoeal Disease Research, Bangladesh (icddr,b). Distinct patterns in seasonality were found for rotavirus diarrhoea which peaked in winter across the sites (December and January) and dipped during the rainy season (May) in urban Dhaka, August in Mirpur and July in Matlab, equated by time-series analysis using quasi-Poisson regression model. Significant seasonality for shigellosis was observed in Dhaka and rural Mirzapur. Cholera had robust seasonality in Dhaka and Matlab in the hot and rainy seasons. For enterotoxogenic Escherichia coli (ETEC) diarrhoea, clearly defined seasonality was observed in Dhaka (summer). Understanding the seasonality of such pathogens can improve case management with appropriate therapy, allowing policy-makers to identify periods of high disease burden.

Capacities, practices and perceptions of evidence-based public health in Europe.

Evidence-based methodologies are used to synthesise systematic high-quality evidence and were first applied in clinical practice. Evidence-based public health, however, is still in its early stages. The European Centre for Disease Prevention and Control sought the insight of European organisations working and providing services in the field of public health on current practices, capacities, perceptions and predictions of evidence-based public health. A survey was sent to 76 organisations. A response rate of 36% was achieved, representing 27 organisations from 16 countries. Systematic reviews were the most commonly offered service, followed by health technology assessments and rapid assessments. Of 25 respondents, 13 believed that evidence-based methodologies were poorly integrated into public health. The main perceived barriers to the further development of evidence-based public health included 'lack of formalised structure or system', 'resource constraints' 'lack of understanding of evidence-based methodologies by policy makers' and 'lack of data'. Nevertheless, 22 of 27 respondents believed that evidence-based methodologies will play an increasingly important role in public health in future. However, several barriers need to be overcome. Consistent frameworks and consensus on best practices were identified as the most pressing requirements. Steps should be taken to address these barriers and facilitate integration and ultimately public health policies.

Groove pancreatitis: a case series and review of the literature.

INTRODUCTION: Groove pancreatitis is a form of chronic pancreatitis affecting the space surrounded by the pancreatic head, duodenum and common bile duct. The clinical findings can conflict with pancreatic cancer causing diagnostic dilemma preoperatively. CASE SERIES: We describe two patients with a history of alcohol excess, who presented with a few months history of upper abdominal pain associated with weight loss and vomiting. Endoscopic and radiological investigations related duodenal narrowing, biliary dilatation and multiple pseudocysts around the head of the pancreas and duodenum. A Whipple's pancreaticoduodenectomy was carried out in both patients. Histopathology report demonstrated cystic areas in both medial and lateral walls of the duodenum microscopically consistent with groove pancreatitis. CONCLUSION: The diagnosis of groove pancreatitis should be considered in patients with duodenal stenosis and cystic lesions around the head of the pancreas associated with history of alcohol excess. Differentiation from pancreatic cancer is difficult preoperatively.

Sequencing and phylogenetic characterisation of a fatal Crimean - Congo haemorrhagic fever case imported into the United Kingdom, October 2012.

A patient with fever, and haemorrhagic symptoms was admitted to a hospital in Glasgow on 2 October 2012. Since he had returned from Afghanistan, serum samples were sent for diagnosis at the Rare and Imported Pathogens Laboratory, where a real-time reverse transcriptase-PCR diagnosis of Crimean ­ Congo haemorrhagic fever was made within 3 hrs after receipt of the sample. Hereafter the patient was transferred to a high-security infectious diseases unit in London but died on 6 October.

The effect of hip and knee arthroplasty on oral anti-inflammatory use and the relationship to body mass index: results from the UK general practice research database.

OBJECTIVE: To determine the use of oral anti-inflammatory drugs in the year before and the 2 years after primary total hip (THR) or knee (TKR) replacement, and whether this varies according to Body mass Index (BMI). DESIGN: 28,068 THR's and 24,364 TKR's, with five matched controls per case were identified from the General Practitioner Research Database. Anti-inflammatory usage was categorized into "zero coverage" - no prescribed anti-inflammatory medication and ">80% coverage" - prescribed anti-inflammatory medication for greater than 80% of the days in the year. Secondary subset analysis was performed according to BMI. RESULTS: 1 year post-surgery the proportion of cases on >80% coverage reduced from 21% (95%confidence interval (CI): 20-22%) to 8% (95%CI: 7-10%) for THR and 21% (95%CI: 20-22%) to 13% (95%CI: 11-14%) for TKR, with no ongoing reduction at 2 years. Zero coverage increased at one and both time points. The proportion of THR's on >80% coverage increased with BMI pre-op. The magnitude in reduction post-op was similar across all BMI groups. The proportion of TKR's on >80% coverage pre-op was greatest in extreme BMI categories. The magnitude in reduction post-op was similar across all BMI groups. CONCLUSION: THR/TKR's reduce the need for anti-inflammatory medication with most benefit observed in the first post-operative year. Increasing BMI affects anti-inflammatory use both in the general population and those undergoing THR/TKR surgery but without strong evidence of a detrimental effect on the benefits of pain relief.

Experiences of LGBTIQA+ People with Disability in Healthcare and Community Services: Towards Embracing Multiple Identities.

Healthcare and disability support services are increasing their efforts towards inclusion and recognising the needs of different groups. This research project was conducted by academic and peer researchers (LGBTIQA+ people with disability) in Victoria, Australia using four focus groups with LGBTIQA+ people with disability. We report on two overarching themes relating to participants' experiences of accessing health services as LGBTIQA+ people with disability: difficulties in managing multiple identities and the impacts of community services and supports. Participants described having to repeatedly 'come out' in a range of ways and contexts as complex and layered processes in which it was difficult to present their full range of needs and experiences to services. We also found that the role of community in promoting a sense of belonging and resilience increased capacity to manage health service use and advocacy. Services and communities aiming to be inclusive to all have the opportunity to recognise and respond to the issues faced by LGBTIQA+ people with disability as a way to pay attention to how overt and subtle practices of discrimination continue to operate despite repeated attempts at or claims of being 'inclusive.' Our research suggests actual inclusive, accessible services can be achieved in part through policy and practice that actively responds to the specific needs of LGBTIQA+ people with disability, in addition to LGBTIQA+ education for disability services and disability and accessibility education for LGBTIQA+ focused services. As we do in this article, we argue that this work must be done by prioritising authentic participation of LGBTIQA+ people with disability in the services and research that is about them.

Maintaining the healthy body: Blood management and hepatitis C prevention among men who inject performance and image-enhancing drugs.

Australia's ambitious aim to 'eliminate' hepatitis C as a public health concern by 2030 requires researchers, policy makers and health practitioners to engage with populations rarely identified as a priority. Men who inject performance and image-enhancing drugs (PIEDs) are one such population, yet research suggests they have low rates of knowledge about hepatitis C. Although rates of needle-sharing in this group are thought to be low, other risks of blood-to-blood contact exist due to the use of large-gauge needles, intramuscular injecting, hard-to-reach injection sites, repeated injecting and peer-to-peer injecting. How should health initiatives engage people who might not customarily consider themselves vulnerable to hepatitis C? Drawing on the work of body theorist Margrit Shildrick, this article considers how men who inject PIEDs understand their bodies, with a particular focus on injecting practices, blood awareness and infection control, in order to inform hepatitis C prevention efforts. In our analysis, we draw on qualitative interviews with 60 men who inject PIEDs, which we conducted for an Australian Research Council-funded project focused on better understanding PIED injecting to improve health and minimise hepatitis C transmission. The interviews suggest that men who inject PIEDs closely monitor potential external infection risks, such as dirt and bacteria that might intrude upon the 'purity and security' of the body. However, less attention appears to be paid to what might be transferred out of the body and potentially to others, such as blood. Notions of trust and cleanliness, and normative perceptions of intravenous drug use, also shaped injecting practices and cursory attention to blood management. While environmental transmission poses a smaller transmission risk than needle-sharing, educating PIED consumers about it is nevertheless warranted. Focusing targeted health promotion materials on environmental blood as a potential route of hepatitis C transmission may help engage this population in prevention, and encourage more frequent hepatitis C testing.

Defining the inside and outside of a catalytic RNA molecule.

Ribozymes are RNA molecules that catalyze biochemical reactions. Fe(II)-EDTA, a solvent-based reagent which cleaves both double- and single-stranded RNA, was used to investigate the structure of the Tetrahymena ribozyme. Regions of cleavage alternate with regions of substantial protection along the entire RNA molecule. In particular, most of the catalytic core shows greatly reduced cleavage. These data constitute experimental evidence that an RNA enzyme, like a protein enzyme, has an interior and an exterior. Determination of positions where the phosphodiester backbone of the RNA is on the inside or on the outside of the molecule provides major constraints for modeling the three-dimensional structure of the Tetrahymena ribozyme. This approach should be generally informative for structured RNA molecules.

Full deflection profile calculation and Young's modulus optimisation for engineered high performance materials.

New engineered materials have critical applications in different fields in medicine, engineering and technology but their enhanced mechanical performances are significantly affected by the microstructural design and the sintering process used in their manufacture. This work introduces (i) a methodology for the calculation of the full deflection profile from video recordings of bending tests, (ii) an optimisation algorithm for the characterisation of Young's modulus, (iii) a quantification of the effects of optical distortions and (iv) a comparison with other standard tests. The results presented in this paper show the capabilities of this procedure to evaluate the Young's modulus of highly stiff materials with greater accuracy than previously possible with bending tests, by employing all the available information from the video recording of the tests. This methodology extends to this class of materials the possibility to evaluate both the elastic modulus and the tensile strength with a single mechanical test, without the need for other experimental tools.

Prostate-specific antigen promoter/enhancer driven gene therapy for prostate cancer: construction and testing of a tissue-specific adenovirus vector.

A range of luciferase reporter vectors was constructed, incorporating 5'-flanking sequences from the prostate-specific antigen (PSA), human glandular kallikrein 2 (hKLK2), and cytomegalovirus (CMV) promoters for expression control. Tissue specificity was evaluated in the PSA-positive line LNCaP and PSA-negative cells from different tissues of origin (CoLo320, DG75, EJ, A2780, and Jurkat). The minimal 628-bp PSA and hKLK2 promoters showed only low-level expression in either PSA-positive or PSA-negative cells and showed no increase with the addition of androgen. Tandem duplication of the PSA promoter slightly increased expression in PSA-positive LNCaP cells. The addition of CMV enhancer sequences upstream of a single PSA or hKLK2 promoter substantially but nonspecifically increased luciferase expression in all cell lines tested. However, placing a 1455-bp PSA enhancer sequence upstream of either the PSA or hKLK2 promoters increased expression 20-fold in the PSA-positive cell line LNCaP but not in the PSA-negative lines. Tandem duplication of the PSA enhancer increased expression to approximately 50-fold higher than either promoter alone while retaining tissue-specific control. The level of expression was reduced by the addition of a third copy of the PSA enhancer. Expression from all enhancer constructs was increased 100-fold above basal levels when induced with the androgen dihydrotestosterone, with the PSA-based constructs consistently exhibiting roughly twice the level of expression of the hKLK2-based constructs at all androgen concentrations. Adenovirus vectors were produced in which either enhanced green fluorescent protein or nitroreductase could be expressed from the optimized PSA double enhancer-promoter construct and evaluated in LNCaP cells and the bladder-derived line EJ. Control vectors with the CMV promoter gave good levels of expression in both cell lines, whereas the PSA constructs only produced detectable levels of protein in the LNCaP cells as assessed by fluorescence of enhanced green fluorescent protein or by Western blotting of nitroreductase. LNCaP but not EJ cells were selectively sensitized to the prodrug CB1954 following infection with Ad-PSA(EEP)-NR. The PSA-based nitroreductase virus produced comparable amounts of nitroreductase and sensitization to CB1954 approaching that of the CMV-driven virus. Plasmid and adenovirus constructs combining PSA enhancer and promoter sequences demonstrate selective expression of linked genes in PSA-positive cells. The expression is induced by androgen and gives therapeutically relevant levels of effector proteins.

Intra-pelvic migration of femoral head trial in total hip arthroplasty, a rare intra-operative complication: a systematic literature review.

Trial reduction while performing total hip replacement is an essential step of the procedure. This is to check the stability of the hip joint with the selected implant sizes and to assess the leg length to avoid discrepancy. Disengagement of the femoral head trial from the femoral rasp stem with subsequent migration of the trial head into the pelvic cavity is a rare occurrence, but can be a very frustrating complication to both the surgeon and occasionally the patient. We present our experience with this exceptional situation and different management options, together with systematic review of the literature.

smg-7 is required for mRNA surveillance in Caenorhabditis elegans.

Eukaryotic mRNAs that contain premature stop codons are degraded more rapidly than their wild-type counterparts, a phenomenon termed "nonsense-mediated mRNA decay" (NMD) or "mRNA surveillance." Functions of six previously described Caenorhabditis elegans genes, smg-1 through smg-6, are required for NMD. Whereas nonsense mutant mRNAs are unstable in smg(+) genetic backgrounds, such mRNAs have normal stability in smg(-) backgrounds. Previous screens for smg mutations have likely not identified all genes involved in NMD, but efforts to identify additional smg genes are limited by the fact that almost 90% of smg mutations identified in genome-wide screens are alleles of smg-1, smg-2, or smg-5. We describe a modified screen for smg mutations that precludes isolating alleles of smg-1, smg-2, and smg-5. Using this screen, we have identified and cloned smg-7, a previously uncharacterized gene that we show is required for NMD. smg-7 is predicted to encode a novel protein that contains an acidic carboxyl terminus and two probable tetratricopeptide repeats. We provide evidence that smg-7 is cotranscribed with the previously characterized gene lin-45 and show that null alleles of smg-7 confer a temperature-sensitive defect in NMD.

Cytokine treatment of human bone marrow activates anti-leukaemia effector cells: monitoring of purging by polymerase chain reaction and DNA analysis.

The aims of this study were to investigate the role of cytokines (tumour necrosis factor alpha (TNF alpha), interferon gamma (IFN gamma) and interleukin-2 (IL-2) in augmenting graft-versus-leukaemia (GVL). We have investigated the effector cells involved in GVL, by studying the role of these cells in purging of the cell line K562 in short-term bone marrow cultures. The effect of the addition in vitro of rGCSF was also studied. Monitoring of purging was achieved by cytotoxicity assays, DNA analysis and the use of the polymerase chain reaction for the detection of bcr/abl transcripts in the Philadelphia positive (Ph+) K562 cell line. Supernatants from IL-2-treated and non-treated bone marrow were tested for cytokine production (TNF alpha and IFN gamma). The results have shown that the main cytotoxic effector cells in the bone marrow generated by IL-2 have the CD56+ CD8+ phenotype. Overnight incubation of bone marrow was sufficient to generate cytotoxic cells as measured by Chromium51 (Cr51) release assays. Measurable levels of TNF alpha but not IFN gamma were also detected in supernatants. Addition of TNF alpha and IFN gamma to the IL-2 in the bone marrow cultures augmented the cytotoxicity but tended to inhibit progenitor cell growth as measured by granulocyte-macrophage colony-forming unit (GM-CFU) and erythroid blast-forming unit (BFU-e) assays. An estimate of the purging of the marrow could also be achieved by DNA analysis of K562 DNA in bone marrow. The bcr/abl transcript could still be detected by PCR analysis in marrow containing 1% K562 and treated with IL-2 for 24 h, but by 6 days of incubation the bcr/abl transcript was weak or undectable. The results suggest that although reduction in the proportion of leukaemia in contaminated marrow can be detected after incubation with IL-2 for 24 h, complete elimination of minimal residual disease requires longer incubation times.

Molecular heterogeneity of variant Philadelphia translocations in childhood acute lymphoblastic leukaemia.

In acute lymphoblastic leukemia (ALL), it is unclear whether variant Philadelphia (Ph) translocations have the same molecular and clinical implications as the classical translocation. Two children with Ph+ ALL with variant translocations are described. One, in whom cytogenetic remission was not achieved, had evidence of translocation of c-abl to chromosome 22, rearrangement of minor breakpoint cluster region (mBCR) and expression of hybrid bcr/abl transcripts. In the other case, no gene rearrangement was found and complete remission was achieved. Variant Ph translocations in childhood ALL are heterogeneous at the molecular level. Molecular studies coupled with observations of clinical outcome are needed in larger numbers of such children to determine whether poor clinical response correlates with bcr/abl involvement and to allow planning of appropriate therapeutic strategies.

Factors influencing the ultrasonic separation of oil-in-water emulsions.

Ultrasound may have inherent shortcomings that preclude its ability to coagulate grease from wastewater, yet these may be overcome by the simultaneous application of electrolysis. We studied the role of pH, conductivity, temperature, ultrasound intensity and duration, and electrolysis voltage, current, and duration, in the study treatment. Conductivity was found to be the most significant factor, however interactions among the eight study variables are likely more important than individual factors. The proposed process was capable of removing up to 100% of grease from the studied wastewater.

It is more than sex and clothes: Culturally safe services for older lesbian, gay, bisexual, transgender and intersex people.

This paper outlines the development of culturally safe services for older lesbian, gay, bisexual, transgender and intersex people. It draws on a framework for cultural safety, developed in New Zealand which incorporates an understanding of how history, culture and power imbalances influence the relationship between service providers and Maori people. This has been adapted to the needs of older lesbian, gay, bisexual, transgender and intersex Australians.