Search for the Pair Production of Dark Particles X with K_{L}

We present the first search for the pair production of dark particles X via K_{L}^{0}→XX with X decaying into two photons using the data collected by the KOTO experiment. No signal was observed in the mass range of 40-110 MeV/c^{2} and 210-240 MeV/c^{2}. This sets upper limits on the branching fractions as B(K_{L}^{0}→XX)<(1-4)×10^{-7} and B(K_{L}^{0}→XX)<(1-2)×10^{-6} at the 90% confidence level for the two mass regions, respectively.

Study of the K_{L}→π

The rare decay K_{L}→π^{0}νν[over ¯] was studied with the dataset taken at the J-PARC KOTO experiment in 2016, 2017, and 2018. With a single event sensitivity of (7.20±0.05_{stat}±0.66_{syst})×10^{-10}, three candidate events were observed in the signal region. After unveiling them, contaminations from K^{±} and scattered K_{L} decays were studied, and the total number of background events was estimated to be 1.22±0.26. We conclude that the number of observed events is statistically consistent with the background expectation. For this dataset, we set an upper limit of 4.9×10^{-9} on the branching fraction of K_{L}→π^{0}νν[over ¯] at the 90% confidence level.

Ana o 1 and Ana o 2 cashew allergens share cross-reactive CD4(+) T cell epitopes with other tree nuts.

BACKGROUND: Allergies to cashew are increasing in prevalence, with clinical symptoms ranging from oral pruritus to fatal anaphylactic reaction. Yet, cashew-specific T cell epitopes and T cell cross-reactivity amongst cashew and other tree nut allergens in humans remain uncharacterized. OBJECTIVES: In this study, we characterized cashew-specific T cell responses in cashew-allergic subjects and examined cross-reactivity of these cashew-specific cells towards other tree nut allergens. METHODS: CD154 up-regulation assay was used to determine immunodominance hierarchy among cashew major allergens at the T cell level. The phenotype, magnitude and functionality of cashew-specific T cells were determined by utilizing ex vivo staining with MHC class II tetramers. Dual tetramer staining and proliferation experiments were used to determine cross-reactivity to other tree nuts. RESULTS: CD4(+) T cell responses were directed towards cashew allergens Ana o 1 and Ana o 2. Multiple Ana o 1 and Ana o 2 T cell epitopes were then identified. These epitopes elicited either TH 2 or TH 2/TH 17 responses in allergic subjects, which were either cashew unique epitope or cross-reactive epitopes. For clones that recognized the cross-reactive epitope, T cell clones responded robustly to cashew, hazelnut and/or pistachio but not to walnut. CONCLUSIONS: Phylogenetically diverse tree nut allergens can activate cashew-reactive T cells and elicit a TH 2-type response at an epitope-specific level. CLINICAL RELEVANCE: Lack of cross-reactivity between walnut and cashew suggests that cashew peptide immunotherapy approach may not be most effective for walnut.

The blood chemical status of Atlantic cod Gadus morhua following capture by jig and demersal longline with differential hook removal methods.

Common haematological [haematocrit (Hct)], primary (serum cortisol) and secondary (serum glucose and plasma lactate) analytes were utilized to compare blood biochemical status of Gadus morhua captured rapidly by jig with that of G. morhua captured by commercial demersal longline. In general, the physiological status of G. morhua, despite blind hook times, was significantly more disrupted (pronounced haemo-concentration and significantly elevated concentrations of cortisol, glucose and lactate) following longline capture relative to capture by jig, while no differences were detected among longline-caught fish as a function of dehooking method (or concomitant extent of overt physical trauma). Blood profiles from the more stressed G. morhua, a possible function of more extended longline hook times, were similar to the most stressed values reported for this species. The results also demonstrate that, although acute blood biochemical status is an effective gauge of relative stress, it does not reflect physical injury status, which has been shown to exert a strong influence on delayed mortality in previous studies in this species. Thus, acute blood chemical status alone may not be the most complete predictor of mortality. Future studies should evaluate physiological repercussions from capture-handling against physical trauma during more extended post-release periods for this species.

Prospective study of the microbiological flora of hearing aid moulds and the efficacy of current cleaning techniques.

INTRODUCTION: Wearing hearing aid earmoulds has been implicated as a predisposing factor in the development of chronic otitis externa. Audiologists come into contact with a large number of hearing aid earmoulds and these could potentially harbour pathogenic micro-organisms, with the risk of subsequent cross infection. Cleaning with dilute alcohol is widely used in an attempt to break the chain of infection. OBJECTIVE: To determine the presence and nature of microbial flora on hearing aid earmoulds and the efficacy of cleaning methods used to prevent cross infection. SETTING: Secondary health care within the audiology department of Addenbrooke's Hospital, Cambridge, UK. DESIGN: A prospective, observational study. METHODS: Hearing aid earmoulds were swabbed before and after cleaning. Samples were cultured to determine qualitatively and quantitatively the microbiological flora present before and after cleaning. RESULTS: Twenty out of 21 (95 per cent) earmoulds had microbes present and, of these, 19/20 (95 per cent) had a polymicrobial profile. Coagulase negative staphylococci and diphtheroids were the most frequent microbial isolates, but pathogenic bacteria and fungi were also demonstrated on earmoulds both before and after cleaning. CONCLUSIONS: The polymicrobial flora, including recognized pathogens, that colonizes earmoulds may lead to chronic otitis externa. Cleaning with 70 per cent alcohol solution was ineffective, in particular for pathogenic fungi on earmoulds.

Neural transplantation in Huntington's disease: the NEST-UK donor tissue microbiological screening program and review of the literature.

Neural transplantation of human fetal tissue for Huntington's disease (HD) is now entering the clinical arena. The safety of the procedure has now been demonstrated in a number of studies, although the efficacy of such an approach is still being investigated. Stringent but practicable screening of the donor tissue for potential pathogens is an essential prerequisite for successful implementation of any novel transplant program that uses human fetal tissue. In this article we summarize the UK-NEST protocol for the screening of human fetal tissue being grafted to patients with mild to moderate HD. We describe the results of microbiological screening of 87 potential tissue donors in a pilot study, and of the first four donor-recipient patients included in the UK-NEST series. The rationale for the adoption and interpretation of the various tests is described and our methodology is compared with those previously used by other centers. This article therefore presents a comprehensive, logical yet pragmatic screening program that could be employed in any clinical studies that use human fetal tissue for neurotransplantation.

Candidaemia in a large teaching hospital: a clinical audit.

BACKGROUND: Candidaemias are associated with significant morbidity and mortality. The British Society of Medical Mycology and Infectious Diseases Society of America recently published audit standards, to address the changing epidemiology of candidaemia and to improve outcomes. AIM: To investigate the local epidemiology of candidaemia and the standard of care in a large teaching hospital. DESIGN: Retrospective audit. METHODS: Data were obtained for all candidaemia episodes over the 4-year period ending July 2004, from the medical and nursing notes, laboratory computer and patient administration system. RESULTS: We identified 92 episodes in 90 patients. The main predisposing factors were being on an intensive care unit, having a central venous catheter, and (for neonates) prematurity. Central venous catheters were removed at a mean 1.8 days following candidaemia; 79% (37/47) were removed within 48 h (the audit standard). Identification and susceptibility tests were performed for 94.7% of isolates. All were susceptible to amphotericin B; 87% were susceptible to fluconazole. Antifungal treatment was started within 24 h of a positive blood culture in 84% of episodes. Initial antifungal therapy was appropriate in 95% (61/64) of treated cases. Most patients (81%) who survived or completed their intended course of treatment before death received at least 2 weeks treatment. However, only 45% of those transferred to other hospitals had accompanying guidance on the intended further duration of therapy. Thirty-day mortality was 41%. After adjustment for age, the presence of Candida-related complications was associated with an odds ratio for mortality of 6.5 (95% CI 1.2-36.5, p = 0.03). DISCUSSION: Overall the audit standards set by the BSMM and IDSA were met, and discrepancies did not lead to a change in outcome. Improved intravenous catheter care, a more pro-active approach to searching for complications, and improvement in the inter-hospital transfer process, will assist in reducing morbidity and mortality.

Guidelines for the control and prevention of meticillin-resistant Staphylococcus aureus (MRSA) in healthcare facilities.

Meticillin-resistant Staphylococcus aureus (MRSA) remains endemic in many UK hospitals. Specific guidelines for control and prevention are justified because MRSA causes serious illness and results in significant additional healthcare costs. Guidelines were drafted by a multi-disciplinary group and these have been finalised following extensive consultation. The recommendations have been graded according to the strength of evidence. Surveillance of MRSA should be undertaken in a systematic way and should be fed back routinely to healthcare staff. The inappropriate or unnecessary use of antibiotics should be avoided, and this will also reduce the likelihood of the emergence and spread of strains with reduced susceptibility to glycopeptides, i.e. vancomycin-intermediate S. aureus/glycopeptide-intermediate S. aureus (VISA/GISA) and vancomycin-resistant S. aureus (VRSA). Screening for MRSA carriage in selected patients and clinical areas should be performed according to locally agreed criteria based upon assessment of the risks and consequences of transmission and infection. Nasal and skin decolonization should be considered in certain categories of patients. The general principles of infection control should be adopted for patients with MRSA, including patient isolation and the appropriate cleaning and decontamination of clinical areas. Inadequate staffing, especially amongst nurses, contributes to the increased prevalence of MRSA. Laboratories should notify the relevant national authorities if VISA/GISA or VRSA isolates are identified.

Unilateral transplantation of human primary fetal tissue in four patients with Huntington's disease: NEST-UK safety report ISRCTN no 36485475.

OBJECTIVES: Huntington's disease (HD) is an inherited autosomal dominant condition in which there is a CAG repeat expansion in the huntingtin gene of 36 or more. Patients display progressive motor, cognitive, and behavioural deterioration associated with progressive cell loss and atrophy in the striatum. Currently there are no disease modifying treatments and current symptomatic treatments are only partially effective in the early to moderate stages. Neural transplantation is effective in animal models of HD and offers a potential strategy for brain repair in patients. The authors report a safety study of unilateral transplantation of human fetal striatal tissue into the striatum of four patients with HD. SUBJECTS AND METHODS: Stereotaxic placements of cell suspensions of human fetal ganglionic eminence were made unilaterally into the striatum of four patients with early to moderate HD. All patients received immunotherapy with cyclosporin A, azathioprine, and prednisolone for at least six months postoperatively. Patients were assessed for safety of the procedure using magnetic resonance imaging (MRI), regular recording of serum biochemistry and haematology to monitor immunotherapy, and clinical assessment according to the Core Assessment Protocol For Intrastriatal Transplantation in HD (CAPIT-HD). RESULTS: During the six month post-transplantation period, the only adverse events related to the procedure were associated with the immunotherapy. MRI demonstrated tissue at the site of implantation, but there was no sign of tissue overgrowth. Furthermore, there was no evidence that the procedure accelerated the course of the disease. CONCLUSIONS: Unilateral transplantation of human fetal striatal tissue in patients with HD is safe and feasible. Assessment of efficacy will require longer follow up in a larger number of patients.

Processing of cardiac valve allografts: 2. Effects of antimicrobial treatment on sterility, structure and mechanical properties.

This is the second in a series of papers that report experiments to investigate the properties required for effective tissue valve implants. This paper is concerned with investigations into alternative antimicrobial treatments and the effect these treatments produce on the structural and biomechanical properties of ovine aortic valves. Six treatments were studied: heat, peracetic acid (at two concentrations), chlorine dioxide, a surfactant cleaning agent and a solvent/detergent treatment. Samples of myocardial tissue were exposed to a mixed bacterial culture or one of three virus cultures and then decontaminated. Two of the six treatments (0.35% peracetic acid and heat) were effective in removing both bacterial and viral contamination, reducing levels of contamination by 2.5 to 3 logs, whilst a third (chlorine dioxide) was effective against viruses ( approximately 3 log reduction). Valves subjected to these treatments were examined by microscopy and measurements of mechanical properties were made. All three treatments seriously damaged endothelial cells and leaflet fibroblasts. Heat treatment also damaged connective tissue components (collagen and elastin) but these changes were not seen after chemical treatment. Mechanical testing confirmed severe damage following heat treatment but chemical treatment showed only minor effects on the elasticity of the leaflets and none on extensibility. These minor effects could be mitigated by exposure to a lower dose of peracetic acid and this treatment could be safely combined with cryopreservation or storage in 85% glycerol. Peracetic acid was the preferred disinfection method for use in the subsequent in vivo studies in sheep.

GRASPing infection: a workload measurement tool for infection control nurses.

The GRASP nursing workload management system was used over a five-month period by both the infection control nurses (ICNs) in an infection control team (ICT) in a 1200-bedded university teaching hospital trust. GRASP data were used to quantify and qualify patient and Trust requirements for infection control (IC). The results indicated that care was being prioritised as the average daily patient care requirement was 15.9 h, whereas the ICNs were only able to provide 12.7 h to meet this. Infection control nurses spent 5.3 h dealing with methicillin-resistant Staphylococcus aureus (MRSA), and only 3.9 h in preparation and delivery of education. A 'fire brigade service' was being provided at the expense of developmental and strategic issues. GRASP provided a method of quantifying, recording and analysing workload. It was used to support recommendations from the Health Quality Service Organizational Audit (Kings Fund), the Department of Health (DoH), the National Audit Office (NAO), and the Health and Safety Executive (HSE) for an increased focus on education and risk management in IC. It was also used in a skill-mix exercise, and resulted in the appointment of additional staffing to the ICT. GRASP data could be used for benchmarking with other institutions to provide a flexible system which may be adapted to meet the changing demands of the health service. It provides a means for ICNs to measure and manage their workload, and may be adapted to other members of the ICT.

Use of light handles in the laminar flow operating theatre--is it a cause of bacterial concern?

Airborne bacteria introduced during routine joint replacement surgery are known to be an important source of joint sepsis with disastrous results. Recently, Robinson et al. [Robinson AHN, Bentley G, Drew S, Anderson J, Ridgway GL. Suction tip contamination in the ultraclean air operating theatre. Ann R Coll Surg Engl 1993; 75: 254-6] have demonstrated that the conventional surgical sucker forms a focus for airborne pathogens which results in septic loosening of hip prostheses. Similarly, the potential contamination of theatre light handles, commonly used during total hip and knee replacements, gives cause for concern. To assess if there was any evidence of contamination, we cultured bacterial swabs taken from the light handles before and after 15 such procedures, all of which were held in a conventional orthopaedic operating theatre. Fortunately, our study found no reason to stop the use of light handles in joint replacement operations.

Effects on nursing workload of different methicillin-resistant Staphylococcus aureus (MRSA) control strategies.

Nursing staff workload may influence hospital-acquired staphylococcal transmission. Closure of wards to new admissions is used in some institutions as part of methicillin-resistant Staphylococcus aureus (MRSA) outbreak control, and we postulated that it worked by reducing staff workload, allowing more time for good infection control practices. We have used the GRASPCopyright workload system to compare nursing workload during six MRSA outbreaks. Two outbreaks occurred while an aggressive control policy ('old'; 1994-1995) was in place, with a low threshold for ward closure. Control measures had been relaxed before the later four outbreaks, with wards remaining fully or partially open unless MRSA transmission proved intractable ('new'; 1995-1996). To standardize the analysis we compared GRASP and epidemiological data for periods while MRSA transmission was occurring on each ward ('during'), and four week periods 'before' and 'after'. Closing wards to admissions reduces staff workload towards a quality environment, although the nursing requirements of remaining patient rises. Workload pressures may rise during outbreaks if wards are not closed quickly and fully, and patients are not transferred to specialist isolation facilities. Changes in nursing workload need to be assessed during comparative studies of outbreak control measures and the GRASP(c) system appears to be a sensitive way to measure these.

Pre-transplantation testing: who, when and why?

An ever-widening range of human organs and tissues is being transplanted, limited currently only by the ingenuity of surgeons and immunologists to overcome the physical and immune barriers. Microbiologists are in danger of being left behind. Although the major infective risks of human organ transplantation are now well understood, many details remain controversial, and the special risks associated with tissue banking have received little attention until recently. What should we do? Are we making mountains out of molehills? Are there any data on which to base a rational decision? Topics covered include: bacteriology of cadaveric heart valve transplantation (why are valves not cultured and only dunked in antibiotic solution for 24h, whereas endocarditis gets treated for 4 weeks?); screening for tissue-born viruses (why does everyone persist with serology when genomic methods are so much better?); screening organ donors for CMV (surely we should use the optimally sensitive combination of methods?); peripheral blood stem cell transplants (should we culture these, and what do the positive results mean if we do?); donor sputum screening before heart-lung transplantation (does this aid the post-operative management of the recipient?). With active participation from the floor some areas of consensus were identified and topics worthy of scientific investigation in the future were highlighted.