Cost-benefit analysis of management practices for ewes lame with footrot

The aim of this study was to investigate the cost-benefit of different strategies to treat and control ovine footrot. In November 2006, 162 sheep farmers in England responded to a survey on prevalence and management of lameness. The costs of lameness per ewe per year (PEPY) were calculated for 116 flocks. Linear regression was used to model the overall cost of lameness PEPY by management method. Associations between farmer satisfaction and time and money spent managing lameness were investigated. The median prevalence of lameness was 5% (inter-quartile range, IQR, 4-10%). The overall cost of lameness PEPY in flocks with ≥10% lameness was UK£6.35 versus £3.90 for flocks with <5% lameness. Parenteral antibiotic treatment was associated with a significantly lower overall cost of lameness by £0.79 PEPY. Routine foot trimming and foot bathing were associated with significantly higher overall costs of lameness PEPY of £2.96 and £0.90, respectively. Farmers satisfied with time managing lameness spent significantly less time (1.46 h PEPY) than unsatisfied farmers (1.90 h PEPY). Farmers satisfied with money spent managing lameness had significantly lower treatment (£2.94 PEPY) and overall (£5.00 PEPY) costs than dissatisfied farmers (£5.50 and £7.60 PEPY, respectively). If the farmers in this study adopted best practice of parenteral antibiotic treatment with no routine foot trimming, and minimised foot bathing for treatment/prevention of interdigital dermatitis, the financial benefits would be approximately £4.65 PEPY. If these costs are similar on other farms the management changes would lead to significant economic benefits for the sheep industry

HIV and tuberculosis co-infection in England, Wales and Northern Ireland: Prevalence, risk factors and transmission

In high-income countries, HIV and tuberculosis are concentrated in hard-to-reach populations. The epidemiology of HIV and tuberculosis co-infection has not been recently described in the UK, and the role of HIV in tuberculosis transmission in low-burden settings is unclear. A systematic review of risk factors for latent tuberculosis infection and active tuberculosis disease was undertaken. The national surveillance datasets for HIV and tuberculosis were linked, and these datasets were used to investigate risk factors for developing tuberculosis for people living with HIV, and to describe trends in HIV co-infection among tuberculosis patients. Strain typing data on Mycobacterium tuberculosis complex isolates from tuberculosis patients were used to examine the role of HIV in tuberculosis transmission. In England, Wales and Northern Ireland, 6.0% of people diagnosed with HIV between 2000 and 2014 had a tuberculosis diagnosis during this time period, and 5.4% of tuberculosis patients were co-infected with HIV. The number and proportion of tuberculosis patients co-infected with HIV declined from 2005 to 2014. The strongest risk factors for tuberculosis among people with HIV were black African ethnicity, birth in a country with high tuberculosis incidence, and HIV acquisition through injecting drug use. High CD4 count and initiating anti-retroviral therapy were both highly protective against tuberculosis. Among tuberculosis patients, drug misuse was the only social risk factor associated with HIV co-infection. Tuberculosis patients with HIV had fewer subsequent clustered cases than HIV-negative tuberculosis patients, and tuberculosis patients with HIV were more often the result of reactivation of latent tuberculosis than recent infection. Co-infection with tuberculosis and HIV has declined, but further reductions are necessary. Increasing screening for HIV and latent tuberculosis in high-risk populations such as people of black African ethnicity, people born in high-incidence countries, and people who inject drugs, could reduce tuberculosis in people living with HIV

Language maintenance in friendships: second-generation German, Greek, and Vietnamese migrants

Our contribution explores the language maintenance (LM) patterns of children of migrants (second-generation) to Australia from three ethnolinguistic groups — German, Greek, and Vietnamese — in their same-age peer friendships. Focusing on the affective social relationship of “friendship” imagined as a dynamic fluid site of independence and a locale for identity formation, we scrutinize it as a pressure point for LM. The macro survey trends indicate that languages other than English (LOTE) are used in the friendship domain but with differing participations. Follow-up in-depth interviews reveal subtleties and complexities for LM practices. Co-presence of bilingual others in friendships proves to be a minimum but not sufficient condition for LM, particularly for German men and Greek women. Hyphenated belongings — for example, Vietnamese-, Greek-, German-Australians — construct varying LM alignments that reflect shared histories and authenticities (the migration experience) and the localizing of settlement (Australia)

A Dual X-Ray Absorptiometry Validated Geometric Model for the Calculation of Body Segment Inertial Parameters of Young Females

The purpose of this study was to validate a new geometric solids model, developed to address the lack of female specific models for body segment inertial parameter estimation. A second aim was to determine the effect of reducing the number of geometric solids used to model the limb segments on model accuracy. The ‘full’ model comprised 56 geometric solids, the ‘reduced’ 31, and the ‘basic’ 16. Predicted whole-body inertial parameters were compared with direct measurements (reaction board, scales), and predicted segmental parameters with those estimated from whole-body DXA scans for 28 females. The percentage root mean square error (%RMSE) for whole-body volume was <2.5% for all models, and 1.9% for the full model. The %RMSE for whole-body center of mass location was <3.2% for all models. The %RMSE whole-body mass was <3.3% for the full model. The RMSE for segment masses was <0.5 kg (<0.5%) for all segments; Bland-Altman analysis showed the full and reduced models could adequately model thigh, forearm, foot and hand segments, but the full model was required for the trunk segment. The proposed model was able to accurately predict body segment inertial parameters for females, more geometric solids are required to more accurately model the trunk

The V-ATPase complex component RNAseK is required for lysosomal hydrolase delivery and autophagosome degradation

Autophagy is a finely orchestrated process required for the lysosomal degradation of cytosoliccomponents. The final degradation step is essential for clearing autophagic cargo and recyclingmacromolecules. Using a CRISPR/Cas9-based screen, we identify RNAseK, a highly conservedtransmembrane protein, as a regulator of autophagosome degradation. Analyses of RNAseK knockout cells reveal that, while autophagosome maturation is intact, cargo degradation is severely disrupted. Importantly, lysosomal protease activity and acidification remain intact in the absence of RNAseK suggesting a specificity to autolysosome degradation. Analyses of lysosome fractions show reduced levels of a subset of hydrolases in the absence of RNAseK. Of these, the knockdown of PLD3 leads to a defect in autophagosome clearance. Furthermore, the lysosomal fraction of RNAseK-depleted cells exhibits an accumulation of the ESCRT-III complex component, VPS4a, which is required for the lysosomal targeting of PLD3. Altogether, here we identify a lysosomal hydrolase delivery pathway required for efficient autolysosome degradation

Patient Self-Testing of Kidney Function at Home, a Prospective Clinical Feasibility Study in Kidney Transplant Recipients

IntroductionPeople with long-term health conditions often attend clinics for kidney function tests. The Self-Testing Own Kidneys (STOK) study assessed feasibility of kidney transplant recipients using hand-held devices to self-test kidney function at home and investigated agreement between home self-test and standard clinic test results.MethodsA prospective, observational, single-center, clinical feasibility study (TRN: ISRCTN68116915), with N = 15 stable kidney transplant recipients, investigated blood potassium and creatinine results agreement between index self-tests at home (patient self-testing of capillary blood, using Abbott i-STAT Alinity analyzers [i-STAT]) and reference tests in clinic (staff sampled venous blood, analyzed with laboratory Siemens Advia Chemistry XPT analyzer) using Bland-Altman and error grid analysis.ResultsThe mean within-patient difference between index and reference test in creatinine was 2.25 μmol/l (95% confidence interval [CI]: −12.13, 16.81 μmol/l) and in potassium was 0.66 mmol/l (95% CI: −1.47, 2.79 mmol/l). All creatinine pairs and 27 of 40 (67.5%) potassium pairs were judged clinically equivalent. Planned follow-up analysis suggests that biochemical variables associated with potassium measurement in capillary blood were predominant sources of paired test result differences. Paired patient and nurse i-STAT capillary blood test potassium results were not statistically significantly different.ConclusionsThis small feasibility study observed that training selected patients to competently use hand-held devices to self-test kidney function at home is possible. Self-test creatinine results showed good analytical and clinical agreement with standard clinic test results. Self-test potassium results showed poorer agreement with standard clinic test results; however, patient use of hand-held devices to self-test at home was not a statistically significant source of paired potassium test result differences

Probability of sepsis after infection consultations in primary care in the United Kingdom in 2002-17:population-based cohort study and decision analytic model

BackgroundEfforts to reduce unnecessary antibiotic prescribing have coincided with increasing awareness of sepsis. We aimed to estimate the probability of sepsis following infection consultations in primary care when antibiotics were or were not prescribed.Methods and findingsWe conducted a cohort study including all registered patients at 706 general practices in the United Kingdom Clinical Practice Research Datalink, with 66.2 million person-years of follow-up from 2002 to 2017. There were 35,244 first episodes of sepsis (17,886, 51%, female; median age 71 years, interquartile range 57-82 years). Consultations for respiratory tract infection (RTI), skin or urinary tract infection (UTI), and antibiotic prescriptions were exposures. A Bayesian decision tree was used to estimate the probability (95% uncertainty intervals [UIs]) of sepsis following an infection consultation. Age, gender, and frailty were evaluated as association modifiers. The probability of sepsis was lower if an antibiotic was prescribed, but the number of antibiotic prescriptions required to prevent one episode of sepsis (number needed to treat [NNT]) decreased with age. At 0-4 years old, the NNT was 29,773 (95% UI 18,458-71,091) in boys and 27,014 (16,739-65,709) in girls; over 85 years old, NNT was 262 (236-293) in men and 385 (352-421) in women. Frailty was associated with greater risk of sepsis and lower NNT. For severely frail patients aged 55-64 years, the NNT was 247 (156-459) in men and 343 (234-556) in women. At all ages, the probability of sepsis was greatest for UTI, followed by skin infection, followed by RTI. At 65-74 years, the NNT following RTI was 1,257 (1,112-1,434) in men and 2,278 (1,966-2,686) in women; the NNT following skin infection was 503 (398-646) in men and 784 (602-1,051) in women; following UTI, the NNT was 121 (102-145) in men and 284 (241-342) in women. NNT values were generally smaller for the period from 2014 to 2017, when sepsis was diagnosed more frequently. Lack of random allocation to antibiotic therapy might have biased estimates; patients may sometimes experience sepsis or receive antibiotic prescriptions without these being recorded in primary care; recording of sepsis has increased over the study period.ConclusionsThese stratified estimates of risk help to identify groups in which antibiotic prescribing may be more safely reduced. Risks of sepsis and benefits of antibiotics are more substantial among older adults, persons with more advanced frailty, or following UTIs

Modelling the dynamics of EBV transmission to inform a vaccine target product profile and future vaccination strategy

Epstein-Barr virus (EBV) is one of the most common human viruses and the cause of pathologies such as infectious mononucleosis (IM) and certain cancers. No vaccine against EBV infection currently exists, but such vaccines are in development. Knowledge of how EBV is transmitted at the population level is critical to the development of target product profles (TPPs) for such vaccines and future vaccination strategies. We present the frst mathematical model of EBV transmission, parameterised using data from England, and use it to compare hypothetical prophylactic vaccines with diferent characteristics and the impact of vaccinating diferent age groups. We found that vaccine duration had more impact than vaccine efcacy on modelled EBV and IM prevalence. The age group vaccinated also had an important efect: vaccinating at a younger age led to a greater reduction in seroprevalence but an increase in IM cases associated with delayed infection. Vaccination had impact on cancer incidence only in the long run, because in England most EBV-related cancers arise in later life. Durability of protection should be a key factor to prioritise in EBV vaccine development and included in vaccine TPPs. These fndings are timely and important for vaccine developers and policy-makers alike

Serious bacterial infections and antibiotic prescribing in primary care: cohort study using electronic health records in the UK

Objective This study evaluated whether serious bacterial infections are more frequent at family practices with lower antibiotic prescribing rates. Design Cohort study. Setting 706 UK family practices in the Clinical Practice Research Datalink from 2002 to 2017. Participants 10.1 million registered patients with 69.3 million patient-years' follow-up. Exposures All antibiotic prescriptions, subgroups of acute and repeat antibiotic prescriptions, and proportion of antibiotic prescriptions associated with specific-coded indications. Main outcome measures First episodes of serious bacterial infections. Poisson models were fitted adjusting for age group, gender, comorbidity, deprivation, region and calendar year, with random intercepts representing family practice-specific estimates. Results The age-standardised antibiotic prescribing rate per 1000 patient-years increased from 2002 (male 423; female 621) to 2012 (male 530; female 842) before declining to 2017 (male 449; female 753). The median family practice had an antibiotic prescribing rate of 648 per 1000 patient-years with 95% range for different practices of 430-1038 antibiotic prescriptions per 1000 patient-years. Specific coded indications were recorded for 58% of antibiotic prescriptions at the median family practice, the 95% range at different family practices was from 10% to 75%. There were 139 759 first episodes of serious bacterial infection. After adjusting for covariates and the proportion of coded consultations, there was no evidence that serious bacterial infections were lower at family practices with higher total antibiotic prescribing. The adjusted rate ratio for 20% higher total antibiotic prescribing was 1.03, (95% CI 1.00 to 1.06, p=0.074). Conclusions We did not find population-level evidence that family practices with lower total antibiotic prescribing might have more frequent occurrence of serious bacterial infections overall. Improving the recording of infection episodes has potential to inform better antimicrobial stewardship in primary care.</p

Helicobacter pylori Membrane Vesicles Stimulate Innate Pro- and Anti-Inflammatory Responses and Induce Apoptosis in Jurkat T Cells

Persistent Helicobacter pylori infection induces chronic inflammation in the human gastric mucosa, which is associated with development of peptic ulceration, gastric atrophy, and gastric adenocarcinoma. It has been postulated that secretion of immunomodulatory molecules by H. pylori facilitates bacterial persistence, and membrane vesicles (MV), which have the potential to cross the gastric epithelial barrier, may mediate delivery of these molecules to host immune cells. However, bacterial MV effects on human immune cells remain largely uncharacterized to date. In the present study, we investigated the immunomodulatory effects of H. pylori MV with and without the vacuolating cytotoxin, VacA, which inhibits human T cell activity. We show a high degree of variability in the toxin content of vesicles between two H. pylori strains (SS1 and 60190). Vesicles from the more toxigenic 60190 strain contain more VacA (s1i1 type) than vesicles from the SS1 strain (s2i2 VacA), but engineering the SS1 strain to produce s1i1 VacA did not increase the toxin content of its vesicles. Vesicles from all strains tested, including a 60190 isogenic mutant null for VacA, strongly induced interleukin-10 (IL-10) and IL-6 production by human peripheral blood mononuclear cells independently of the infection status of the donor. Finally, we show that H. pylori MV induce T cell apoptosis and that this is enhanced by, but not completely dependent on, the carriage of VacA. Together, these findings suggest a role for H. pylori MV in the stimulation of innate pro- and anti-inflammatory responses and in the suppression of T cell immunity