An evaluation of detailed animal characteristics influencing the lactation production efficiency of spring-calving, pasture-based dairy cattle.

Selection for feed efficiency, the ratio of output (e.g., milk yield) to feed intake, has traditionally been limited on commercial dairy farms by the necessity for detailed individual animal intake and performance data within large animal populations. The objective of the experiment was to evaluate the effects of individual animal characteristics (animal breed, genetic potential, milk production, body weight (BW), daily total dry matter intake (TDMI), and energy balance) on a cost-effective production efficiency parameter calculated as the annual fat and protein (milk solids) production per unit of mid-lactation BW (MSperBWlact). A total of 1,788 individual animal intake records measured at various stages of lactation (early, mid, and late lactation) from 207 Holstein-Friesian and 200 Jersey × Holstein-Friesian cows were used. The derived efficiency traits included daily kilograms of milk solids produced per 100 kg of BW (dMSperBWint) and daily kilograms of milk solids produced per kilogram of TDMI (dMSperTDMI). The TDMI per 100 kg of BW was also calculated (TDMI/BWint) at each stage of lactation. Animals were subsequently either ranked as the top 25% (Heff) or bottom 25% (Leff) based on their lactation production efficiency (MSperBWlact). Dairy cow breed significantly affected animal characteristics over the entire lactation and during specific periods of intake measurements. Jersey crossbred animals produced more milk, based on a lower TDMI, and achieved an increased intake per kilogram of BW. Similarly, Heff produced more milk over longer lactations, weighed less, were older, and achieved a higher TDMI compared with the Leff animals. Both Jersey × Holstein-Friesian and Heff cows achieved superior production efficiency due to lower maintenance energy requirements, and consequentially increased milk solids production per kilogram of BW and per kilogram of TDMI at all stages of lactation. Indeed, within breed, Heff animals weighed 20 kg less and produced 15% more milk solids over the total lactation than Leff. In addition, Heff achieved increased daily milk solids yield (+0.16 kg) and milk solids yield per kilogram of TDMI (+ 0.23 kg/kg DM) during intake measurement periods. Moreover, the strong and consistently positive correlations between MSperBWlact and detailed production efficiency traits (dMSperBWint, dMSperTDMI) reported here demonstrate that MSperBWlact is a robust measure that can be applied within commercial grazing dairy systems to increase the selection intensity for highly efficient animals.

COVID-19 outbreaks in care homes during the first wave: are Care Quality Commission ratings a good predictor of at-risk homes?

BACKGROUND: COVID-19 placed a significant burden on the care home population during the first wave. Care Quality Commission's care quality ratings are given to all English care homes and could be used to identify whether care homes are at risk of COVID-19 outbreaks. METHODS: An audit was performed, April 2020, of Liverpool care homes to identify associations between COVID-19 status and care quality ratings from the Care Quality Commission. Univariable logistic regression was performed to identify whether the Care Quality Commissions ratings were associated with a care home experiencing a COVID-19 outbreak, or a home having asymptomatic cases. FINDINGS: Over half of the care homes (53.2%, n=41), had laboratory-confirmed clinical cases and 39 (95.1%) of these were reported as outbreaks. A small number of care homes (10.4%, n=8) had asymptomatic cases and over a third had no clinical or asymptomatic cases (36.4%, n=28). There was no significant difference between the overall Care Quality Commission rating of Liverpool and English care homes (p=0.57). There was no significant association between any of the Care Quality Commission rating domains and the presence of COVID-19 outbreaks and/or asymptomatic cases. CONCLUSIONS: During the first wave of the COVID-19 pandemic, Care Quality Commission ratings were not associated with COVID-19 outbreaks or asymptomatic cases in care homes. Infection prevention and control components of Care Quality Commission ratings need to be strengthened to identify care homes at a potential risk of infectious disease outbreaks that may require targeted support. Further large-scale studies will be required to test the findings from this study.

COVID-19 testing in outbreak-free care homes: what are the public health benefits?

BACKGROUND: COVID-19 care home outbreaks represent a significant proportion of COVID-19 morbidity and mortality in the UK. National testing initially focused on symptomatic care home residents, before extending to asymptomatic cohorts. AIM: The aim was to describe the epidemiology and transmission of COVID-19 in outbreak free care homes. METHODS: A two-point prevalence survey of COVID-19, in 34 Liverpool care homes, was performed in April and May 2020. Changes in prevalence were analysed. Associations between care home characteristics, reported infection, prevention and control interventions, and COVID-19 status were described and analysed. FINDINGS: No resident developed COVID-19 symptoms during the study. There was no significant difference between: the number of care homes containing at least one test positive resident between the first (17.6%, 95% confidence interval (CI) 6.8-34.5) and second round (14.7%, 95% CI 5.0-31.1) of testing (p>0.99); and the number of residents testing positive between the first (2.1%, 95% CI 1.2-3.4) and second round (1.0%, 95% CI 0.5-2.1) of testing (P=0.11). Care homes providing nursing care (risk ratio (RR) 7.99, 95% CI 1.1-57.3) and employing agency staff (RR 8.4, 95% CI 1.2-60.8) were more likely to contain test positive residents. Closing residents shared space was not associated with residents testing positive (RR 2.63, 95% CI 0.4-18.5). CONCLUSIONS: Asymptomatic COVID-19 care homes showed no evidence of disease transmission or development of outbreaks; suggesting that current infection prevention and control measures are effective in preventing transmission. Repeat testing at two to three weeks had limited or no public health benefits over regular daily monitoring of staff and residents for symptoms. These results should inform policies calling for regular testing of asymptomatic residents.

L-alpha-amino adipic acid provokes depression-like behaviour and a stress related increase in dendritic spine density in the pre-limbic cortex and hippocampus in rodents.

Astrocyte dysfunction is implicated in clinical depression. There is a paucity of animal models to assess the role of astrocytes in depression pathogenesis. Refinement of an existing model is described here. Administration of the astrocytic toxin L-alpha aminoadipic acid (L-AAA) to the pre-limbic cortex (PLC) was assessed in rats and mice in tests of anxiety and depression related behaviours. Delivery of L-AAA to the PLC of Wistar rats produced an increase in immobility in the forced swimming test (FST) and reduced exploration in the open field. Delivery to the CA3 subfield of the hippocampus produced a deficit in the novel object relocation task. Delivery of single or two successive doses of L-AAA to the PLC of C57Bl6/J mice was sufficient to induce an increase in immobility in the mouse tail suspension (TST) and FST independently of administration of anaesthetic agent or the surgical procedure. In both mice and rats, L-AAA produced a reduction in immunoreactivity of the astrocytic marker glial fibrillary acidic protein (GFAP) for up to 72 h. L-AAA provoked an increase in the density of apical and basal dendritic spines in mice exposed to the FST when compared to non-FST controls. In summary, L-AAA provokes a region-dependent change in behaviour, a reduction in GFAP immunoreactivity and FST-provoked increased in dendritic spine density in the PLC. This model may be further employed to assess the impact of astroglial integrity on the structural plasticity of neurons and the effect of antidepressant agents on L-AAA-related changes.

JNK1 controls adult hippocampal neurogenesis and imposes cell-autonomous control of anxiety behaviour from the neurogenic niche.

Promoting adult hippocampal neurogenesis is expected to induce neuroplastic changes that improve mood and alleviate anxiety. However, the underlying mechanisms remain largely unknown and the hypothesis itself is controversial. Here we show that mice lacking Jnk1, or c-Jun N-terminal kinase (JNK) inhibitor-treated mice, display increased neurogenesis in adult hippocampus characterized by enhanced cell proliferation and survival, and increased maturation in the ventral region. Correspondingly, anxiety behaviour is reduced in a battery of tests, except when neurogenesis is prevented by AraC treatment. Using engineered retroviruses, we show that exclusive inhibition of JNK in adult-born granule cells alleviates anxiety and reduces depressive-like behaviour. These data validate the neurogenesis hypothesis of anxiety. Moreover, they establish a causal role for JNK in the hippocampal neurogenic niche and anxiety behaviour, and advocate targeting of JNK as an avenue for novel therapies against affective disorders.

Multi-year evaluation of stocking rate and animal genotype on milk production per hectare within intensive pasture-based production systems.

The objective of this experiment was to evaluate the effect of stocking rate (SR) and animal genotype (BR) on milk production, body weight (BW), and body condition score (BCS) within intensive pasture-based systems. A total of 533 lactation records, from 246 elite genetic merit dairy cows were available for analysis; 68 Holstein-Friesian (HF) and 71 Jersey × Holstein-Friesian (JxHF) crossbred cows in each of 4 consecutive years (2013-2016, inclusive). Cows from each BR were randomly allocated to 1 of 3 whole-farm comparative SR treatments, low (LSR; 1,200 kg of BW/ha), medium (MSR; 1,400 kg of BW/ha), and high (HSR; 1,600 kg of BW/ha), and remained in the same SR treatments for the duration of the experiment. The effects of SR, BR, and their interaction on milk production/cow and per hectare, BW, BCS, and grazing characteristics were analyzed. Total pasture utilization per hectare consumed in the form of grazed pasture increased linearly as SR increased: least in LSR (10,237 kg of dry matter/ha), intermediate in MSR (11,016 kg of dry matter/ha), and greatest in HSR (11,809 kg of dry matter/ha). Milk and milk solids (MS) yield per hectare was greatest for HSR (15,942 and 1,354 kg, respectively), intermediate for MSR (14,191 and 1,220 kg, respectively), and least for LSR (13,186 and 1,139 kg, respectively) with similar trends evident for fat, protein, and lactose yield/ha. At higher SR (MSR and HSR), MS yield per kg of BW per ha was reduced (0.85 and 0.82 kg of MS/kg of BW, respectively) compared with LSR (0.93 kg of MS/kg of BW/ha). Holstein-Friesian cows achieved fewer grazing days per hectare (-37 d), and produced more milk (+561 kg/ha) but less fat plus protein (-57 kg/ha) compared with JxHF cows; the JxHF cows were lighter. At similar BW per hectare, JxHF cows produced more fat plus protein/ha during the grazing season at low (1,164 vs. 1,113 kg), medium (1,254 vs. 1,185 kg), and high (1,327 vs. 1,380 kg) SR. In addition, JxHF cows produced more fat plus protein per kg of BW/ha (0.90 kg) compared with HF cows (0.84 kg). The results highlight the superior productive efficiency of high genetic potential crossbred dairy cows within intensive pasture-based production systems.

JNK1 controls adult hippocampal neurogenesis and imposes cell-autonomous control of anxiety behaviour from the neurogenic niche.

This corrects the article DOI: 10.1038/mp.2016.203.

Effect of stocking rate and animal genotype on dry matter intake, milk production, body weight, and body condition score in spring-calving, grass-fed dairy cows.

The objective of the experiment was to quantify the effect of stocking rate (SR) and animal genotype on milk production, dry matter intake (DMI), energy balance, and production efficiency across 2 consecutive grazing seasons (2014 and 2015). A total of 753 records from 177 dairy cows were available for analysis: 68 Holstein-Friesian and 71 Jersey × Holstein-Friesian (JxHF) cows each year of the experiment under a pasture-based seasonal production system. Animals within each breed group were randomly allocated to 1 of 3 whole-farm SR treatments defined in terms of body weight per hectare (kg of body weight/ha): low (1,200 kg of body weight/ha), medium (1,400 kg of body weight/ha), and high (1,600 kg of body weight/ha), and animals remained in the same SR treatments for the duration of the experiment. Individual animal DMI was estimated 3 times per year at grass using the n-alkane technique: March (spring), June (summer), and September (autumn), corresponding to 45, 111, and 209 d in milk, respectively. The effects of SR, animal genotype, season, and their interactions were analyzed using mixed models. Milk production, body weight, and production efficiency per cow decreased significantly as SR increased due to reduced herbage availability per cow and increased grazing severity. As a percentage of body weight, JxHF cows had higher feed conversion efficiency, higher DMI and milk solids (i.e., kg of fat + kg of protein) production, and also required less energy intake to produce 1 kg of milk solids. The increased production efficiency of JxHF cows at a similar body weight per hectare in the current analysis suggests that factors other than individual cow body weight contribute to the improved efficiency within intensive grazing systems. The results highlight the superior productive efficiency of high genetic potential crossbred dairy cows within intensive pasture-based milk production systems at higher SR where feed availability is restricted.

Milk production and fertility performance of Holstein, Friesian, and Jersey purebred cows and their respective crosses in seasonal-calving commercial farms.

There is renewed interest in dairy cow crossbreeding in Ireland as a means to further augment productivity and profitability. The objective of the present study was to compare milk production and fertility performance for Holstein, Friesian, and Jersey purebred cows, and their respective crosses in 40 Irish spring-calving commercial dairy herds from the years 2008 to 2012. Data on 24,279 lactations from 11,808 cows were available. The relationship between breed proportion, as well as heterosis and recombination coefficients with performance, was quantified within a mixed model framework that also contained the fixed effects of parity; cow and contemporary group of herd-year-season of calving were both included as random effects in the mixed model. Breed proportion was associated with all milk production parameters investigated. Milk yield was greatest for Holstein (5,217kg), intermediate for Friesian (4,591kg), and least for Jersey (4,230kg), whereas milk constituents (i.e., fat and protein concentration) were greatest for Jersey (9.38%), intermediate for Friesian (7.91%), and least for Holstein (7.75%). Yield of milk solids in crossbred cows exceeded their respective parental average performance; greatest milk solids yield (i.e., fat kg + protein kg) was observed in the Holstein × Jersey first-cross, yielding 25kg more than the mid-parent mean. There was no consistent breed effect on the reproductive traits investigated. Relative to the mid-parent mean, Holstein × Jersey cows calved younger as heifers and had a shorter calving interval. Friesian × Jersey first-cross cows also had a shorter calving interval relative to their mid-parent mean. Results were consistent with findings from smaller-scale controlled experiments. Breed complementarity and heterosis attainable from crossbreeding resulted in superior animal performance and, consequently, greater expected profitability in crossbred cows compared with their respective purebreds.

The "5Es" of emergency physician-performed focused cardiac ultrasound: a protocol for rapid identification of effusion, ejection, equality, exit, and entrance.

Emergency physician (EP)-performed focused cardiac ultrasound (EP FOCUS) has been increasingly recognized as a crucial tool to help clinicians diagnose and treat potentially life-threatening conditions. The existing literature demonstrates a variety of EP FOCUS applications and protocols; however, EP FOCUS is not taught, practiced, or interpreted consistently between institutions. Drawing on over 12 years of experience in a large-volume, high-acuity academic emergency department, we have developed a protocol for teaching and performing EP FOCUS known as "The 5Es," where each E represents a specific assessment for immediately relevant clinical information. These include pericardial effusion, qualitative left ventricular ejection, ventricular equality, exit (aortic root diameter), and entrance (inferior vena cava diameter and respirophasic variation). Each of these assessments has been well described in the emergency medicine literature and is within the scope of EP-performed echocardiography. This approach provides a reliable and easily recalled framework for assessing, teaching, and communicating EP FOCUS findings that are essential in caring for the patient in the emergency setting.

Lysosomal alkalization and dysfunction in human fibroblasts with the Alzheimer's disease-linked presenilin 1 A246E mutation can be reversed with cAMP.

Mutation in presenilin 1 (PS1) is one of the leading causes of familial Alzheimer's disease (fAD). PS1 mutation exacerbates the autophagic and lysosomal pathology in AD patients, leading to accumulation of partially degraded material in bloated lysosomes and autophagosomes - a pathology that bears some resemblance to other diseases characterized by elevated lysosomal pH, like age-related macular degeneration. In this study, we examined the effect of the PS1-fAD mutation A246E on lysosomal pH and lysosomal function, and asked whether restoration of lysosomal pH could reverse some of these changes. Lysosomal pH was elevated by 0.2-0.3 pH units in human fibroblasts with the PS1-fAD mutation. The lysosomal alkalization in PS1-fAD fibroblasts was supported by a reduction in the pH-dependent cleavage of cathepsin D and by a reduction in binding of boron-dipyrromethene (BODIPY) FL-pepstatin A to the cathepsin D active site. PS1-fAD cells had increased LC3B-II/-I ratios and p62 levels, consistent with impaired lysosomal degradation and analogous to changes induced by lysosomal alkalinization with chloroquine. PS1-fAD fibroblasts had increased expression of ATP6V1B2, ATG5, BECN1 TFEB mRNA, and of ATP6V1B2, ATG5 and beclin at the protein level, consistent with chronic impairment of autophagic and lysosomal functions in the mutant cells. Critically, cyclic adenosine monophosphate (cAMP) treatment reacidified lysosomal pH in mutant PS1-fAD; cAMP also increased the availability of active cathepsin D and lowered the LC3B-II/-I ratio. These results confirm a small elevation in the lysosomal pH of human PS1-fAD fibroblasts, demonstrate that this lysosomal alkalization is associated with chronic changes in autophagy and degradation, and suggest that treatment to reacidify the lysosomes with cAMP can reverse these changes.

An ongoing large outbreak of measles in Merseyside, England, January to June 2012.

From 1 January to 30 June 2012, 359 confirmed and 157 probable cases of measles were reported in Merseyside, England. The most affected age groups were children under five years and young adults from 15 years of age. Most cases have been sporadic. There have been few outbreaks in nurseries; however, no outbreaks have been reported in schools. Of the cases eligible for vaccination, only 3% of the confirmed cases were fully immunised.

Secular trends in the occurrence of tuberculosis in an urban community in north west England, 1918-2001: implications for a local tuberculosis control programme.

In recent years enhanced surveillance of tuberculosis has been undertaken for England and Wales to monitor national epidemiological trends. The Chief Medical Officer's strategy for communicable diseases has identified the development of a national strategy for the control of tuberculosis as a priority. Regional and sub-regional variations in the occurrence of tuberculosis require further exploration to inform local implementation of the national strategy. Secular epidemiological trends in tuberculosis for the period 1918-2001 are described for a deprived urban area in the north west of England, and implications for local enhanced surveillance and control measures are discussed. A substantial decline in mortality and morbidity from tuberculosis is shown due to interruption of transmission following improvements to the housing stock and the introduction of chemotherapy and BCG vaccination. The proportion of incident cases of tuberculosis in non-white groups has markedly increased over the period observed. The local tuberculosis control programme now specifically targets recent non-white immigrants. Other urban areas may need to adopt similar measures to improve local control of tuberculosis.

Activation of the MKK4-JNK pathway during erythroid differentiation of K562 cells is inhibited by the heat shock factor 2-beta isoform.

In this study we report the activation of c-Jun N-terminal kinase (JNK) in human K562 erythroleukemia cells undergoing hemin-mediated erythroid differentiation, which occurs concomitantly with activation of heat shock factor 2 (HSF2) and leads to a simultaneous in vivo phosphorylation of c-Jun. The activation of JNK occurs through activation of mitogen-activated protein kinase kinase (MKK) 4 and not by activation of MKK7 or inhibition of JNK-directed phosphatases. We have previously shown that overexpression of the HSF2-beta isoform inhibits the activation of HSF2 upon hemin-induced erythroid differentiation. Here we demonstrate that HSF2-beta overexpression blocks the hemin-induced activation of the MKK4-JNK pathway, suggesting an erythroid lineage-specific JNK activation likely to be regulated by HSF2.

Expression profiling using microarrays fabricated by an ink-jet oligonucleotide synthesizer.

We describe a flexible system for gene expression profiling using arrays of tens of thousands of oligonucleotides synthesized in situ by an ink-jet printing method employing standard phosphoramidite chemistry. We have characterized the dependence of hybridization specificity and sensitivity on parameters including oligonucleotide length, hybridization stringency, sequence identity, sample abundance, and sample preparation method. We find that 60-mer oligonucleotides reliably detect transcript ratios at one copy per cell in complex biological samples, and that ink-jet arrays are compatible with several different sample amplification and labeling techniques. Furthermore, results using only a single carefully selected oligonucleotide per gene correlate closely with those obtained using complementary DNA (cDNA) arrays. Most of the genes for which measurements differ are members of gene families that can only be distinguished by oligonucleotides. Because different oligonucleotide sequences can be specified for each array, we anticipate that ink-jet oligonucleotide array technology will be useful in a wide variety of DNA microarray applications.

The heart of the matter: an essay about the effects of managed care on family therapy with children.

This essay is based on a pilot study that examined the effects of managed care on the treatment of children and families, with special attention to community mental health. We embarked on the pilot study to test the accuracy and generalizability of our impression that family therapy and other systemic practices have been marginalized in ordinary clinics and agencies, and to understand the reasons why. We interviewed managed care providers, researchers, family therapy trainers, and clinicians in the Northeast. Our findings led to seven themes that support our impression that, even though there is a consensus about the need for coordinated family-based services, there is a disconnection between state policies, contractual requirements and what is actually occurring at the implementation level. This study suggests that our knowledge of human systems may be in danger of being disqualified and lost, with damaging consequences for the care of children. Yet, as systemic thinkers and practitioners, it is our belief that ethical and effective treatment need not be at odds with care that is cost-efficient. The direction of our future research will be to study whether the involvement of all stakeholders at all levels of planning and training leads to systemic family-based practices that consistently save costs and provide high-quality care.

Dual roles for c-Jun N-terminal kinase in developmental and stress responses in cerebellar granule neurons.

c-Jun N-terminal kinases (JNKs) typically respond strongly to stress, are implicated in brain development, and are believed to mediate neuronal apoptosis. Surprisingly, however, JNK does not respond characteristically to stress in cultured cerebellar granule (CBG) neurons, a widely exploited CNS model for studies of death and development, despite the regulation of its substrate c-Jun. To understand this anomaly, we characterized JNK regulation in CBG neurons. We find that the specific activity of CBG JNK is elevated considerably above that from neuron-like cell lines (SH-SY5Y, PC12); however, similar elevated activities are found in brain extracts. This activity does not result from cellular stress because the stress-activated protein kinase p38 is not activated. We identify a minor stress-sensitive pool of JNK that translocates with mitogen-activated protein kinase kinase-4 (MKK4) into the nucleus. However, the major pool of total activity is cytoplasmic, residing largely in the neurites, suggesting a non-nuclear role for JNK in neurons. A third JNK pool is colocalized with MKK7 in the nucleus, and specific activities of both increase during neuritogenesis, nuclear JNK activity increasing 10-fold, whereas c-Jun expression and activity decrease. A role for JNK during differentiation is supported by modulation of neuritic architecture after expression of dominant inhibitory regulators of the JNK pathway. Channeling of JNK signaling away from c-Jun during differentiation is consistent with the presence in the nucleus of the JNK/MKK7 scaffold protein JNK-interacting protein, which inhibits JNK-c-Jun interaction. We propose a model in which distinct pools of JNK serve different functions, providing a basis for understanding multifunctional JNK signaling in differentiating neurons.

Functional discovery via a compendium of expression profiles.

Ascertaining the impact of uncharacterized perturbations on the cell is a fundamental problem in biology. Here, we describe how a single assay can be used to monitor hundreds of different cellular functions simultaneously. We constructed a reference database or "compendium" of expression profiles corresponding to 300 diverse mutations and chemical treatments in S. cerevisiae, and we show that the cellular pathways affected can be determined by pattern matching, even among very subtle profiles. The utility of this approach is validated by examining profiles caused by deletions of uncharacterized genes: we identify and experimentally confirm that eight uncharacterized open reading frames encode proteins required for sterol metabolism, cell wall function, mitochondrial respiration, or protein synthesis. We also show that the compendium can be used to characterize pharmacological perturbations by identifying a novel target of the commonly used drug dyclonine.

Burns caused by medical therapy.

A burn injury may occur as an unexpected consequence of medical treatment. We examined the burn prevention implications of injuries received in a medical treatment facility or as a direct result of medical care. The records of 4510 consecutive admissions to 1 burn center between January 1978 and July 1997 were retrospectively reviewed. A cohort of 54 patients burned as a result of medical therapy was identified and stratified by location (home vs medical facility) and by mechanism of injury. Twenty-two patients were burned in a medical treatment facility, including 12 patients who were burned as a result of careless or unsupervised use of tobacco products. Thirty-two patients were burned as a result of home medical therapy, including 9 patients who had scald injuries from vaporizers, 8 patients who were burned by simultaneous use of cigarettes and home nasal oxygen therapy, and 11 patients who were burned by therapeutic application of heat. In contrast to previous studies, no patient was burned by the use of medical laser devices. To further decrease burn risk from medical therapy we advocate the prohibition of cigarette smoking in any medical facility. Continued tobacco use may represent a contraindication to home oxygen therapy. Given the lack of proof of efficacy combined with the potential for burn injury, the use of vaporizers to treat upper respiratory symptoms should be discouraged. Patients with diminished sensation or altered mental status are at increased risk of burn injury from bathing or topical heat application and merit closer monitoring during these activities.