Evaluation of an on-farm culture system for the detection of subclinical mastitis pathogens in dairy cattle.

The purpose of this observational study was to compare the performance of a novel on-farm culture (OFC) test with the reference method (RM) in identifying pathogens, and in particular Staphylococcus aureus, associated with subclinical mastitis (SCM) in dairy cattle. The OFC test (Mastatest HiSCC; Mastaplex Limited) for SCM uses a cartridge with 2 × 12 wells allowing 1 sample to be analyzed in duplicate (24 wells) or 2 samples analyzed simultaneously, each in 12 wells. Results of the milk analyses are reported hierarchically (Staph. aureus → coagulase-negative staphylococci (CNS) → other gram positive or coliform/gram negative → no bacteria present) and emailed within 24 h. Milk samples (617 quarter level from 158 cows and 70 cow level) were collected from 288 cows [individual cow somatic cell count (ICSCC) ≥150,000 cells/mL] on 9 purposefully selected farms known to have a high prevalence of clinical and subclinical Staph. aureus mastitis in Southland New Zealand. Quarter samples were analyzed individually (617 samples) and after animal-level pooling, providing 228 (158 + 70) cow-level samples. Samples were analyzed by the OFC test (in duplicate) and the RM (culture agar medium and latex test based on the recommendation by the National Mastitis Council) and identifications confirmed with MALDI-TOF mass spectrometry. Sensitivity (Se), specificity (Sp), positive predictive value (PPV), and negative predictive value (NPV) for detection of Staph. aureus were all ∼90% with tight 95% confidence limits, and Cohen's kappa (κ) for agreement between the OFC test and RM was 0.81. Kappa for agreement between the OFC test duplicates was 0.93. About 35% of cows had only one quarter infected with Staph. aureus and all these animals could still be identified when pooled cow-level milk was analyzed. Although the high prevalence of Staph. aureus in the herds used in this study does not affect the Se and Sp values, it does elevate the PPV value (and decrease the NPV) and therefore use of PPV to extrapolate to a population with lower prevalence is not appropriate. For CNS, Sp, PPV, and NPV were all >0.8, κ was ≥0.6, and Se was >0.7. Kappa for agreement between the OFC test duplicates was 0.83. A result of "no bacteria detected" was reported in 13% of the cows with 93% agreement between OFC test and RM. We conclude that the OFC test provides a reliable method for detecting Staph. aureus in pooled cow-level milk even if only one quarter is infected; in the absence of Staph. aureus in the milk, it reliably identified CNS in pooled cow-level milk; it reliably identified cows with <10 cfu/10 µL of their milk. Compared with the RM, the method was rapid with results returned in 24 h of loading the cartridge.

Exploring mental health disability gaps in the labour market: the UK experience during COVID-19.

People with long-term mental health problems that affect their daily activities are a growing proportion of the UK working population and they have a particularly low employment rate. We analyse gaps in labour market outcomes between mental health disabled and non-disabled people during the COVID-19 pandemic in the UK. We also decompose the outcome gaps in order to explore the relative importance of different factors in explaining these gaps. Our results suggest that the employment effects of the pandemic for mental health disabled people may have been temporary. However, they were more likely to be away from work and/or working reduced hours than people without a disability. Workers with mental health disability were over-represented in part-time work and in caring, leisure and other service occupations, which were disproportionately affected by COVID-19 and the economic response. This is important new evidence on the contribution of segmentation and segregation in explaining the labour market position of people with mental health disability. The longer term effects of the pandemic were still not apparent at the end of our analysis period (2021:Q3), but the concentration of disabled workers in cyclically sensitive sectors and part-time work means that they will always be particularly vulnerable to economic downturns.

Employment related COVID-19 exposure risk among disabled people in the UK.

We provide new evidence about the work-related exposure of disabled people to COVID-19 using household survey data combined with a novel occupational risk indicator. Despite their higher clinical vulnerability, disabled people in employment in the UK were significantly more likely to be going out to work during the pandemic rather than working from home, and were working in occupations that were more exposed to COVID-19 than the occupations of non-disabled workers. Our results raise questions about whether there are sufficient safeguards for disabled people in the workplace, and have longer-term implications for a labour market where COVID-19 is a persistent health issue.

The effect of mental and physical health problems on sickness absence.

Absenteeism is an important feature of the labour market, imposing significant costs on employers and the economy as a whole. This paper is the first to use a large labour force survey sample to investigate how different physical and mental health conditions affect absence rates among prime age workers in the UK. A pooled time series/cross-section analysis reveals that people with a chronic health condition are more likely to be absent from work, and mental health has a significantly larger effect than physical health. From a longitudinal perspective, we find that a change in mental health has an effect on absenteeism more than three times greater than a change in physical health. These findings imply that the prevention and alleviation of chronic health conditions, particularly common mental disorders such as depression and anxiety that are highly prevalent in prime age workers, will deliver significant benefits to the UK economy due to reduced absenteeism. Further, there is significant heterogeneity between different health conditions, with some having no effect at all on absenteeism having controlled for other factors.

Weak Magnetic Fields Enhance the Efficacy of Radiation Therapy.

PURPOSE: The clinical efficacy of radiation therapy is mechanistically linked to ionization-induced free radicals that cause cell and tissue injury through direct and indirect mechanisms. Free radical reaction dynamics are influenced by many factors and can be manipulated by static weak magnetic fields (WMF) that perturb singlet-triplet state interconversion. Our study exploits this phenomenon to directly increase ionizing radiation (IR) dose absorption in tumors by combining WMF with radiation therapy as a new and effective method to improve treatment. METHODS AND MATERIALS: Coils were custom made to produce both homogeneous and gradient magnetic fields. The gradient coil enabled simultaneous in vitro assessment of free radical/reactive oxygen species reactivity across multiple field strengths from 6 to 66 G. First, increases in IR-induced free radical concentrations using oxidant-sensitive fluorescent dyes in a cell-free system were measured and verified. Next, human and murine cancer cell lines were evaluated in in vitro and in vivo models after exposure to clinically relevant doses of IR in combination with WMF. RESULTS: Cellular responses to IR and WMF were field strength and cell line dependent. WMF was able to enhance IR effects on reactive oxygen species formation, DNA double-strand break formation, cell death, and tumor growth. CONCLUSIONS: We demonstrate that the external presence of a magnetic field enhances radiation-induced cancer cell injury and death in vitro and in vivo. The effect extends beyond the timeframe when free radicals are induced in the presence of radiation into the window when endogenous free radicals are produced and therefore extends the applicability of this novel adjunct to cancer therapy in the context of radiation treatment.

Analysis of Human Acupoint Biological Information and Neural Electric Activity Based on Ultrasonographic Image.

To find out the bioelectric signal discriminative features of different acupoints at the same time and at the same acupoint, and then analyze these differences to determine the type of acupuncture points and assist in judging the patient's condition, a hardware system was designed that can collect subcutaneous potential information of acupoints. Then, the changes of ultrasonic images were analyzed after acupuncture at Zu San Li, as well as the influence of acupuncture at Zu San Li on vagal nerve activity. The hardware system is composed of 4 parts: an analog circuit module, a digital circuit module, a power module, and a host personal computer. The power module adopted dual-module power supply mode, which was composed of MC78M05CT and LM2576 and their related peripheral circuits to ensure the stability of the circuit. The analog circuit module collected the electric signals from the 2 acupoints of Zu San Li and Shang Ju Xu of the volunteers' calves through a multistage electrode probe. In the amplifier module, Butterworth filter and 50 HZ notch are used to reduce the noise of electric signals. The filtered and amplified electric signals are converted into A/D converter in the digital circuit module. Serial communication is used to transmit data to the upper computer of the personal computer to compare the noise reduction effect of acupoint information, multiple sequences of different acupoints, and multiple sequences of the same acupoint. The influence of acupuncture at the Zu San Li acupoint on the muscle tension around the acupoint was investigated by shear wave acoustic elastic imaging technology. The influence of acupuncture at this acupoint was explored on vagal nerve activity. The results show that the wavelet noise reduction method can greatly filter out the interference signals. In the case of artificial stimulation, the signal waveform of each twist shows a big increase, and the comparison shows that there is no significant change in the frequency of other bands. Through ultrasonic image evaluation, it was found that acupuncture at Zu San Li can significantly affect the mean value of Young modulus. After acupuncture at Zu San Li, the vagal activity was increased and the balance ratio of sympathetic vagal activity was reduced. Part of the potential frequency of the acupoint is extremely active, which is the response potential of the subcutaneous induction tissue at the acupoint, which proved the feasibility of collecting electric signals around the acupoints in this kind of hardware system. It is of great significance to diagnose the disease according to the characteristics of acupoint electric signals.

Treatment of Left Ventricular Circulation Disorder: Application of Echocardiography Information Data Monitoring.

BACKGROUND: Cardiac hypertrophy induced by pressure overload is one of the important causes of heart failure and sudden cardiac death. At present, there are few studies on the outcome of left ventricular hypertrophy and left ventricular function after complete pressure load removal. OBJECTIVE: This study aims to better simulate the changes of left ventricular structure and function during the process of left ventricular pressure overload and deloading, and to explore the application of echocardiography in it. METHODS: In this study, healthy male (BALB/C) mice were used as research objects to establish an ascending aorta constriction model, to carry out echocardiographic and hemodynamic examinations, to establish an ascending aorta deconstriction model in mice, and to carry out echocardiographic and hemodynamic examinations. RESULTS: Compared with the sham operation group, the left ventricular end-systolic diameter (LVESD), left ventricular end-diastolic diameter (LVEDD), interventricular septal (IVS), and left ventricular posterior wall (LVPW) in the constriction operation group were significantly increased (P=.02, P=.02, P=.02, and P=.02, respectively). LVESD, LVEDD, IVS, and LVPW in the early and late constriction groups were significantly decreased, and the degree of decrease in the early group was greater than that in the late group; compared with the sham operation group, left ventricular diastolic pressure in the constriction operation group increased significantly at 9 and 15 weeks after operation (P=.03). Left ventricular systolic pressure at 15 weeks after operation decreased to a certain extent but was higher than that of the sham operation group (P=.02). The maximal rate of the increase of left ventricular pressure at 3 weeks, 9 weeks, and 15 weeks after operation decreased significantly (P=.03, P=.02, and P=.02, respectively). CONCLUSIONS: In this study, the ascending aorta coarctation model and descending aorta coarctation model were successfully established, which verifies the value of echocardiography information data monitoring in the treatment of left ventricular circulation disorders and the evaluation of surgical treatment.

Mechanisms of ß-lactam resistance of Streptococcus uberis isolated from bovine mastitis cases.

A number of veterinary clinical pathology laboratories in New Zealand have been reporting emergence of increased minimum in inhibitory concentrations for ß-lactams in the common clinical bovine mastitis pathogen Streptococcus uberis. The objective of this study was to determine the genetic basis of this increase in MIC for ß-lactams amongst S. uberis. Illumina sequencing and determination of oxacillin MIC was performed on 265 clinical isolates. Published sequences of the five penicillin binding proteins pbp1a, pbp1b, pbp2a, pbp2b, and pbp2x were used to identify, extract and align these sequences from the study isolates. Amino acid substitutions resulting from single nucleotide polymorphisms (SNP) within these genes were analysed for associations with elevated (≥ 0.5 mg/L) oxacillin MIC together with a genome wide association study. The population structure of the study isolates was approximated using a phylogenetic tree generated from an alignment of the core genome. A total of 53 % of isolates had MIC ≥ 0.5 mg/L for oxacillin. A total of 101 substitutions within the five pbp were identified, of which 11 were statistically associated with an MIC ≥ 0.5 mg/L. All 140 isolates which exhibited an increased ß-lactam MIC had SNPs leading to pbp2x E381K and Q554E substitutions. The phylogenetic tree indicated that the genotype and phenotype associated with the increased MIC for oxacillin were present in several different lineages suggesting that acquisition of this increased ß-lactam MIC had occurred in multiple geographically distinct regions. Reanalysis of the data from the intervention studies from which the isolates were originally drawn found a tendency for the pbp2x E381K substitution to be associated with lower cure rates. It is concluded that there is geographically and genetically widespread presence of pbp substitutions associated with reduced susceptibility to ß-lactam antimicrobials. Additionally, presence of pbp substitutions tended to be associated with poorer cure rate outcomes following antimicrobial therapy for clinical mastitis.

The SIPHER Consortium: Introducing the new UK hub for systems science in public health and health economic research.

The conditions in which we are born, grow, live, work and age are key drivers of health and inequalities in life chances. To maximise health and wellbeing across the whole population, we need well-coordinated action across government sectors, in areas including economic, education, welfare, labour market and housing policy. Current research struggles to offer effective decision support on the cross-sector strategic alignment of policies, and to generate evidence that gives budget holders the confidence to change the way major investment decisions are made. This open letter introduces a new research initiative in this space. The SIPHER ( Systems Science in Public Health and Health Economics Research) Consortium brings together a multi-disciplinary group of scientists from across six universities, three government partners at local, regional and national level, and ten practice partner organisations. The Consortium's vision is a shift from health policy to healthy public policy, where the wellbeing impacts of policies are a core consideration across government sectors. Researchers and policy makers will jointly tackle fundamental questions about: a) the complex causal relationships between upstream policies and wellbeing, economic and equality outcomes; b) the multi-sectoral appraisal of costs and benefits of alternative investment options; c) public values and preferences for different outcomes, and how necessary trade-offs can be negotiated; and d) creating the conditions for intelligence-led adaptive policy design that maximises progress against economic, social and health goals. Whilst our methods will be adaptable across policy topics and jurisdictions, we will initially focus on four policy areas: Inclusive Economic Growth, Adverse Childhood Experiences, Mental Wellbeing and Housing.

A Bioreactor Technology for Modeling Fibrosis in Human and Rodent Precision-Cut Liver Slices.

Precision cut liver slices (PCLSs) retain the structure and cellular composition of the native liver and represent an improved system to study liver fibrosis compared to two-dimensional mono- or co-cultures. The aim of this study was to develop a bioreactor system to increase the healthy life span of PCLSs and model fibrogenesis. PCLSs were generated from normal rat or human liver, or fibrotic rat liver, and cultured in our bioreactor. PCLS function was quantified by albumin enzyme-linked immunosorbent assay (ELISA). Fibrosis was induced in PCLSs by transforming growth factor beta 1 (TGFß1) and platelet-derived growth factor (PDGFßß) stimulation ± therapy. Fibrosis was assessed by gene expression, picrosirius red, and α-smooth muscle actin staining, hydroxyproline assay, and soluble ELISAs. Bioreactor-cultured PCLSs are viable, maintaining tissue structure, metabolic activity, and stable albumin secretion for up to 6 days under normoxic culture conditions. Conversely, standard static transwell-cultured PCLSs rapidly deteriorate, and albumin secretion is significantly impaired by 48 hours. TGFß1/PDGFßß stimulation of rat or human PCLSs induced fibrogenic gene expression, release of extracellular matrix proteins, activation of hepatic myofibroblasts, and histological fibrosis. Fibrogenesis slowly progresses over 6 days in cultured fibrotic rat PCLSs without exogenous challenge. Activin receptor-like kinase 5 (Alk5) inhibitor (Alk5i), nintedanib, and obeticholic acid therapy limited fibrogenesis in TGFß1/PDGFßß-stimulated PCLSs, and Alk5i blunted progression of fibrosis in fibrotic PCLS. Conclusion: We describe a bioreactor technology that maintains functional PCLS cultures for 6 days. Bioreactor-cultured PCLSs can be successfully used to model fibrogenesis and demonstrate efficacy of antifibrotic therapies.

Flexible working in the UK and its impact on couples' time coordination.

The ability to combine work with quality time together as a family is at the heart of the concept of work-life balance. Using previously unexploited data on couples' work schedules we investigate the effect of flexible working on couples' coordination of their daily work schedules in the UK. We consider three distinct dimensions of flexible working: flexibility of daily start and finish times (flexitime), flexibility of work times over the year (annualized hours), and generalized control of working hours. We show that having flexitime at work increases a couple's amount of coordination of their daily work schedules by a half to 1 h, which is double the margin of adjustment enjoyed by couples with no flexitime. The impact is driven by couples with children. In contrast to flexitime, the other two forms of flexible working do not seem to increase synchronous time. Our results suggest that having flexitime plays an important role in relaxing the work scheduling constraints faced by families with young children, and that effective flexible working time arrangements are those that increase the worker's and not the employer's flexibility.

Does housework lower wages? Evidence for Britain.

This paper uses the British Household Panel Survey to present the first estimates of the housework-wage relationship in Britain. Controlling for permanent unobserved heterogeneity, we find that housework has a negative impact on the wages of men and women, both married and single, who work full-time. Among women working part-time, only single women suffer a housework penalty. The housework penalty is uniform across occupations within full-time jobs but some part-time jobs appear to be more compatible with housework than others. We find tentative evidence that the housework penalty is larger when there are children present.

Periparturient use of parenteral micronised procaine penicillin to reduce the risk of clinical mastitis in heifers after calving.

Mastitis in primiparous heifers immediately postpartum can be both a significant welfare concern and a heavy economic loss. Interventions successfully researched include intramammary therapies. This study considered the clinical and practical effects of a parenteral approach to controlling clinical mastitis in heifers immediately postpartum. The objective of this field trial was to determine whether preventative treatment of heifers with a single parenteral treatment of 15 million iu micronised procaine penicillin within 12h after calving would reduce the incidence of clinical mastitis in early lactation as detected by farmers. All heifers (n=609) calving on three commercial dairy farms in New Zealand during the spring of 2006 were randomly allocated to either treatment or no treatment. Treatment (15 million iu micronised procaine penicillin) was given at the first milking following calving. All clinical mastitis was recorded. Treatment reduced the odds of having clinical mastitis within the first 7 days in milk by over half (Mantel-Haenszel adjusted OR=0.456; p=0.044); and reduced the odds of having mastitis within the first 100 days in milk by just under half (Mantel-Haenszel adjusted OR=0.518; p=0.027). Treatment had a significant effect on increasing the median days to clinical mastitis (p=0.019; beta=1.961, LCI 1.117, UCI 3.445). Preventative treatment of heifers immediately following calving with 15 million iu micronised procaine penicillin parenterally could be of benefit as part of a control programme aimed at reducing the incidence of clinical mastitis in heifers in their first lactation.