Early detection of subclinical mastitis in lactating dairy cows using cow-level features.

Subclinical mastitis in cows affects their health, well-being, longevity, and performance, leading to reduced productivity and profit. Early prediction of subclinical mastitis can enable dairy farmers to perform interventions to mitigate its effect. The present study investigated how well predictive models built using machine learning techniques can detect subclinical mastitis up to 7 d before its occurrence. The data set used consisted of 1,346,207 milk-day (i.e., a day when milk was collected on both morning and evening) records spanning 9 yr from 2,389 cows producing on 7 Irish research farms. Individual cow composite milk yield and maximum milk flow were available twice daily, whereas milk composition (i.e., fat, lactose, protein) and somatic cell count (SCC) were collected once per week. Other features describing parity, calving dates, predicted transmitting ability for SCC, body weight, and history of subclinical mastitis were also available. The results of the study showed that a gradient boosting machine model trained to predict the onset of subclinical mastitis 7 d before a subclinical case occurs achieved a sensitivity and specificity of 69.45 and 95.64%, respectively. Reduced data collection frequency, where milk composition and SCC were recorded only every 15, 30, 45, and 60 d was simulated by masking data, to reflect the frequency of recording of this data on commercial dairy farms in Ireland. The sensitivity and specificity scores reduced as recording frequency reduced with respective scores of 66.93 and 80.43% when milk composition and SCC were recorded just every 60 d. Results demonstrate that models built on data that could be recorded routinely available on commercial dairy farms, can achieve useful predictive ability of subclinical mastitis even with reduced frequency of milk composition and SCC recording.

Using genomics to examine the persistence of Streptococcus pneumoniae serotype 19A in Ireland and the emergence of a sub-clade associated with vaccine failures.

BACKGROUND: Streptococcus pneumoniae serotype 19A remains a significant cause of invasive pneumococcal disease (IPD) in Ireland despite the successful introduction of a 13-valent pneumococcal conjugate vaccine (PCV13) in 2010 which reduced the overall incidence of IPD in children. METHODS: Invasive Streptococcus pneumoniae serotype 19A isolates from the Irish reference laboratory between 2007-08 and 2017-18 were analysed using whole genome sequencing (WGS) to investigate the persistence of this vaccine-preventable serotype. We compared the entire national 19A collection to other international collections using a standardised nomenclature of Global Pneumococcal Sequencing Clusters (GPSC). RESULTS: Expansion of GPSCs and clonal complexes (CCs) may have been associated with vaccine introduction and antimicrobial prescribing policies. A sub-clade of GPSC1-CC320 (n = 25) unique to Ireland, included five of the ten vaccine failures/breakthrough cases identified (p = 0.0086). This sub-clade was not observed in a global GPSC1-CC320 collection. All isolates within the sub-clade (n = 25) contained a galE gene variant rarely observed in a global pneumococcal collection (n = 37/13454, p < 0.001) nor within GPSC1-CC320 (n = 19/227) (p < 0.001). The sub-clade was estimated to have emerged at the start of the PCV-vaccine era (ancestral origin 2000, range 1995-2004) and expanded in Ireland, with most isolated after PCV13 introduction (n = 24/25). CONCLUSIONS: The identification of a sub-clade/variant of serotype 19A highlights the benefit of using WGS to analyse genotypes associated with persistence of a preventable serotype of S. pneumoniae. Particularly as this sub-clade identified was more likely to be associated with IPD in vaccinated children than other 19A genotypes. It is possible that changes to the galE gene, which is involved in capsule production but outside of the capsular polysaccharide biosynthesis locus, may affect bacterial persistence within the population. Discrete changes associated with vaccine-serotype persistence should be further investigated and may inform vaccine strategies.

Is It Time To Review The Vaccination Strategy To Protect Adults Against Invasive Pneumococcal Disease?

Pneumococcal conjugate vaccines (PCVs) have reduced the predominant serotypes causing invasive pneumococcal disease (IPD). We assessed the impact of the paediatric 7- and 13-valent pneumococcal conjugate vaccines (PCV7 and PCV13) among older adults. We compared serotype-specific incidence rates from 2007/08 to 2016/17, expressed as incidence rate ratios (IRR). Introducing PCV7 and PCV13 into the childhood immunisation programme resulted in a decline in these serotypes in adults ≥65 years of age, with PCV7 serotypes decreasing by 85% (IRR=0.11, 95%CI: 0.05-0.22, p<0.0001) and PCV13 serotypes not included in PCV7 (PCV13-7), decreasing by 9% (IRR=0.68, 95%CI: 0.40-1.16, p=0.134). However, there was a significant increase in serotypes only found in the 23-valent polysaccharide vaccine, PPV23-PCV13: IRR=2.57, 95%CI: 1.68-4.03, p<0.0001, and non-vaccine types (NVTs), IRR=3.33, 95%CI: 1.75-6.84, p=0.0001. The decline of IPD associated with PCV7/13 serotypes and the increase in PPV23-PCV13 serotypes indicates clear serotype replacement. Increasing PPV23 uptake could still reduce the burden of disease for this population.

The epidemiology of invasive pneumococcal disease in older adults in the post-PCV era. Has there been a herd effect?

The 7 and 13-valent pneumococcal conjugate vaccines (PCVs) have reduced the incidence of invasive pneumococcal disease (IPD) in children in many countries. The objective of this work was to assess the impact of PCVs and potential herd-protection in older adults in Ireland. IPD notification and typing data from adults ⩾65 years of age from July 2007 to June 2016 was assessed using national surveillance data. There was a 94% reduction in PCV7 serotypes from 2007-2008 to 2015-2016, incidence rate ratio (IRR 0·05, P < 0·0001). However, there was no decline in the additional PCV13 (PCV13-7) serotypes over the same period (IRR 0·90) nor in comparison with the pre-PCV13 period 2009-2010 (IRR 0·92). The incidence of serotypes in the 23-valent pneumococcal polysaccharide vaccine only (PPV23-PCV13) and non-vaccine types (NVTs) increased significantly (IRR 2·17, P = 0·0002 and IRR 3·43, P = 0·0001 respectively). Consequently, the overall IPD incidence rate in adults has remained relatively unchanged (from 28·66/100 000 to 28·88/100 000, IRR 1·01, P = 0·9477). Serotype 19A and NVTs were mainly responsible for penicillin resistance in recent years. The decline of PCV7 serotypes indicate that the introduction of PCV7 resulted in herd-protection for adults. However, increases in PPV23-PCV13 and NVTs suggest that changes in vaccination strategy amongst older adults are needed to build on the success of PCVs in children.

Accelerometer Assessment of Physical Activity and Its Association with Physical Function in Older Adults Residing at Assisted Care Facilities.

OBJECTIVES: To describe levels of physical activity among older adults residing at assisted care facilities and their association with physical function. DESIGN: Cross-sectional analysis. SETTING: Assisted care facilities within the greater Boston, MA area. PARTICIPANTS: Older adults aged 65 years and older (N = 65). MEASUREMENTS: Physical Activity Level (PAL) as defined by quartiles from accelerometry (counts and steps), Short Physical Performance Battery (SPPB) Score, gait speed, and handgrip strength. RESULTS: Participants in the most active accelerometry quartile engaged in 25 minutes/week of moderate to vigorous physical activity (MVPA) and walked 2,150 steps/day. These individuals had an SPPB score, 400 meter walk speed, and handgrip strength that was 3.7-3.9 points, 0.3-0.4 meters/second, and 4.5-5.1 kg greater respectively, than individuals in the lowest activity quartile, who engaged in less than 5 min/wk of MVPA or took fewer than 460 steps/day. CONCLUSION: Despite engaging in physical activity levels far below current recommendations (150 min/week of MVPA or > 7000 steps/day), the most active older adults in this study exhibited clinically significant differences in physical function relative to their less active peers. While the direction of causality cannot be determined from this cross-sectional study, these findings suggest a strong association between PAL and physical function among older adults residing in an assisted care facility.

Dissemination of clonally related multidrug-resistant Klebsiella pneumoniae in Ireland.

In October 2012, an outbreak of gentamicin-resistant, ciprofloxacin non-susceptible extended-spectrum ß-lactamase (ESBL)-producing Klebsiella pneumoniae occurred in a neonatal intensive care unit in Ireland. In order to determine whether the outbreak strain was more widely dispersed in the country, 137 isolates of K. pneumoniae with this resistance phenotype collected from 17 hospitals throughout Ireland between January 2011 and July 2013 were examined. ESBL production was confirmed phenotypically and all isolates were screened for susceptibility to 19 antimicrobial agents and for the presence of genes encoding bla TEM, bla SHV, bla OXA, and bla CTX-M; 22 isolates were also screened for bla KPC, bla NDM, bla VIM, bla IMP and bla OXA-48 genes. All isolates harboured bla SHV and bla CTX-M and were resistant to ciprofloxacin, gentamicin, nalidixic acid, amoxicillin-clavulanate, and cefpodoxime; 15 were resistant to ertapenem, seven to meropenem and five isolates were confirmed as carbapenemase producers. Pulsed-field gel electrophoresis of all isolates identified 16 major clusters, with two clusters comprising 61% of the entire collection. Multilocus sequence typing of a subset of these isolates identified a novel type, ST1236, a single locus variant of ST48. Data suggest that two major clonal groups, ST1236/ST48 (CG43) and ST15/ST14 (CG15) have been circulating in Ireland since at least January 2011.

Diagnosis of viral gastroenteritis in children: interpretation of real-time PCR results and relation to clinical symptoms.

Molecular methods such as real-time polymerase chain reaction (PCR) are rapidly replacing traditional tests to detect fecal viral pathogens in childhood diarrhea. This technique has now increased the analytical sensitivity so drastically that positive results are found in asymptomatic children, leading to complex interpretation of real-time PCR results and difficult distinction between asymptomatic shedding and etiological cause of disease. We performed a review of the literature including pediatric studies using real-time PCR and a minimal inclusion period of one year to exclude bias by seasonality. We searched for studies on rotavirus, norovirus, adenovirus, astrovirus, and sapovirus, known to be the most common viruses to cause gastroenteritis in the pediatric population. For these viruses, we summarized the detection rates in hospitalized and community-based children with clinical symptoms of gastroenteritis, as well as subjects with asymptomatic viral shedding. Moreover, insight is given into the different viral sero- and genotypes causing pediatric gastroenteritis. We also discuss the scoring systems for severity of disease and their clinical value. A few published proposals have been made to improve the clinical interpretation of real-time PCR results, which we recapitulate and discuss in this review. We propose using the semi-quantitative measure of real-time PCR, as a surrogate for viral load, in relation to the severity score to distinguish asymptomatic viral shedding from clinically relevant disease. Overall, this review provides a better understanding of the scope of childhood gastroenteritis, discusses a method to enhance the interpretation of real-time PCR results, and proposes conditions for future research to enhance clinical implementation.

Commonly used disinfectants fail to eradicate Salmonella enterica biofilms from food contact surface materials.

Salmonellosis is the second most common cause of food-borne illness worldwide. Contamination of surfaces in food processing environments may result in biofilm formation with a risk of food contamination. Effective decontamination of biofilm-contaminated surfaces is challenging. Using the CDC biofilm reactor, the activities of sodium hypochlorite, sodium hydroxide, and benzalkonium chloride were examined against an early (48-h) and relatively mature (168-h) Salmonella biofilm. All 3 agents result in reduction in viable counts of Salmonella; however, only sodium hydroxide resulted in eradication of the early biofilm. None of the agents achieved eradication of mature biofilm, even at the 90-min contact time. Studies of activity of chemical disinfection against biofilm should include assessment of activity against mature biofilm. The difficulty of eradication of established Salmonella biofilm serves to emphasize the priority of preventing access of Salmonella to postcook areas of food production facilities.

Salmonella enterica biofilm formation and density in the Centers for Disease Control and Prevention's biofilm reactor model is related to serovar and substratum.

Foodborne pathogens can attach to, and survive on, food contact surfaces for long periods by forming a biofilm. Salmonella enterica is the second most common cause of foodborne illness in Ireland. The ability of S. enterica to form a biofilm could contribute to its persistence in food production areas, leading to cross-contamination of products and surfaces. Arising from a large foodborne outbreak of S. enterica serovar Agona associated with a food manufacturing environment, a hypothesis was formulated that the associated Salmonella Agona strain had an enhanced ability to form a biofilm relative to other S. enterica. To investigate this hypothesis, 12 strains of S. enterica, encompassing three S. enterica serovars, were assessed for the ability to form a biofilm on multiple food contact surfaces. All isolates formed a biofilm on the contact surfaces, and there was no consistent trend for the Salmonella Agona outbreak strain to produce a denser biofilm compared with other strains of Salmonella Agona or Salmonella Typhimurium. However, Salmonella Enteritidis biofilm was considerably less dense than Salmonella Typhimurium and Salmonella Agona biofilms. Biofilm density was greater on tile than on concrete, polycarbonate, stainless steel, or glass.

Recurrent dedifferentiated paratesticular liposarcoma with synchronous renal cell carcinoma and prostate cancer.

Paratesticular liposarcoma is a very rare cause of scrotal mass. It is thought that they arise from spermatic cord lipomas most commonly. While well differentiated tumors tend to share many histological similarities with dedifferentiated tumors, the latter has a much more aggressive phenotype. We present an unusual case of a 69-year-old male with synchronous prostate adenocarcinoma and unilateral renal cell carcinoma who was found to have a dedifferentiated paratesticular liposarcoma. Treatment was with radical resection, preserving the testis, followed by radiotherapy. Unusually recurrence did not occur until 4 years following initial treatment. This case demonstrates the high propensity of dedifferentiated liposarcoma to recur locally and examines the most frequently employed management strategies.

Diagnosis of bladder cancer by immunocytochemical detection of minichromosome maintenance protein-2 in cells retrieved from urine.

BACKGROUND: We tested the accuracy of immunocytochemistry (ICC) for minichromosome maintenance protein-2 (MCM-2) in diagnosing bladder cancer, using cells retrieved from urine. METHODS: Adequate samples were obtained from 497 patients, the majority presenting with gross haematuria (GH) or undergoing cystoscopic surveillance (CS) following previous bladder cancer. We performed an initial study of 313 patients, followed by a validation study of 184 patients. In all cases, presence/absence of bladder cancer was established by cystoscopy/biopsy. RESULTS: In the initial study, receiver operator characteristic analysis showed an area under the curve of 0.820 (P<0.0005) for the GH group and 0.821 (P<0.01) for the CS group. Optimal sensitivity/specificity were provided by threshold values of 50+ MCM-2-positive cells in GH samples and 200+ cells in CS samples, based on a minimum total cell number of 5000. Applying these thresholds to the validation data set gave 81.3% sensitivity, 76.0% specificity and 92.7% negative predictive value (NPV) in GH and 63.2% sensitivity, 89.9% specificity and 89.9% NPV in CS. Minichromosome maintenance protein-2 ICC provided clinically relevant improvements over urine cytology, with greater sensitivity in GH and greater specificity in CS (P=0.05). CONCLUSIONS: Minichromosome maintenance protein-2 ICC is a reproducible and accurate test that is suitable for both GH and CS patient groups.

Search for the rare decays K(L)→π0π0µ+µ- and K(L)→π0π0X0→π0π0µ+µ-.

The KTeV E799 experiment has conducted a search for the rare decays, K(L)→π(0)π(0)µ(+)µ(-) and K(L)→π(0)π(0)X(0)→π(0)π(0)µ(+)µ(-), where the X(0) is a possible new neutral boson that was reported by the HyperCP experiment with a mass of (214.3 ± 0.5) MeV/c(2). We find no evidence for either decay. We obtain upper limits of Br(K(L)→π(0)π(0)X(0)→π(0)π(0)µ(+)µ(-)) < 1.0 × 10(-10) and Br(K(L)→π(0)π(0)µ(+)µ(-)) < 9.2 × 10(-11) at the 90% confidence level. This result rules out the pseudoscalar X(0) as an explanation of the HyperCP result under the scenario that the dsX(0) coupling is completely real.

Regional changes in gene expression after limbic kindling.

Repeated electrical stimulation results in development of seizures and a permanent increase in seizure susceptibility (kindling). The permanence of kindling suggests that chronic changes in gene expression are involved. Kindling at different sites produces specific effects on interictal behaviors such as spatial cognition and anxiety, suggesting that causal changes in gene expression might be restricted to the stimulated site. We employed focused microarray analysis to characterize changes in gene expression associated with amygdaloid and hippocampal kindling. Male Long-Evans rats received 1 s trains of electrical stimulation to either the amygdala or hippocampus once daily until five generalized seizures had been kindled. Yoked control rats carried electrodes but were not stimulated. Rats were euthanized 14 days after the last seizures, both amygdala and hippocampus dissected, and transcriptome profiles compared. Of the 1,200 rat brain-associated genes evaluated, 39 genes exhibited statistically significant expression differences between the kindled and non-kindled amygdala and 106 genes exhibited statistically significant differences between the kindled and non-kindled hippocampus. In the amygdala, subsequent ontological analyses using the GOMiner algorithm demonstrated significant enrichment in categories related to cytoskeletal reorganization and cation transport, as well as in gene families related to synaptic transmission and neurogenesis. In the hippocampus, significant enrichment in gene expression within categories related to cytoskeletal reorganization and cation transport was similarly observed. Furthermore, unique to the hippocampus, enrichment in transcription factor activity and GTPase-mediated signal transduction was identified. Overall, these data identify specific and unique neurochemical pathways chronically altered following kindling in the two sites, and provide a platform for defining the molecular basis for the differential behaviors observed in the interictal period.

The effects of the European Working Time Directive on surgical training: the basic surgical trainee's perspective.

BACKGROUND: On the 1 August 2009, the implementation of European Working Time Directive became European law and was implemented in Galway University Hospital (GUH). AIMS: The aim of the study is to ascertain the opinion of the 25 surgical SHOs in GUH on the effect of the implementation of an EWTD compliant roster had on the quality of their training. METHODS: A questionnaire was circulated to all 25 surgical SHOs. RESULTS: Twenty-two (88%) SHOs report a reduction in the quality of their training. 18 (72%) report a reduction in the development of their operative skills. The SHOs believed the EWTD Rotas would encourage Irish graduates to train abroad. CONCLUSIONS: Surgical training faces a challenge with the implementation of EWTD Rotas. Major changes need to be made to the surgical training structure to train surgeons to the highest standard and to retain Irish-trained surgeons in the Irish healthcare system.

Recombinant activated factor VII to control life-threatening haemorrhagic radiation cystitis.

INTRODUCTION: The use of recombinant activated factor VII has been described for many clinical scenarios, but the value of this therapeutic agent for life-threatening haemorrhagic cystitis remains novel. METHOD: We describe a case of persistent life-threatening haemorrhagic radiation cystitis, and discuss current knowledge of this therapy including potential complications. RESULT: Control of haemorrhage was successfully achieved only after use of this agent. CONCLUSION: This therapy deserves mention in any future management algorithm devised for this condition.

Cell death induced by dexamethasone in lymphoid leukemia is mediated through initiation of autophagy.

Glucocorticoids are fundamental drugs used in the treatment of lymphoid malignancies with apoptotic cell death as the hitherto proposed mechanism of action. Recent studies, however, showed that an alternative mode of cell death, autophagy, is involved in the response to anticancer drugs. The specific role of autophagy and its relationship to apoptosis remains, nevertheless, controversial: it can either lead to cell survival or can function in cell death. We show that dexamethasone induced autophagy upstream of apoptosis in acute lymphoblastic leukemia cells. Inhibition of autophagy by siRNA-mediated repression of Beclin 1 expression inhibited apoptosis showing an important role of autophagy in dexamethasone-induced cell death. Dexamethasone treatment caused an upregulation of promyelocytic leukemia protein, PML, its complex formation with protein kinase B or Akt and a PML-dependent Akt dephosphorylation. Initiation of autophagy and the onset of apoptosis were both dependent on these events. PML knockout thymocytes were resistant to dexamethasone-induced death and upregulation of PML correlated with the ability of dexamethasone to kill primary leukemic cells. Our data reveal key mechanisms of dexamethasone-induced cell death that may inform the development of improved treatment protocols for lymphoid malignancies.

Renal trauma in the west of Ireland--a regional review.

We herein present a regional review of the management of renal trauma in the west of Ireland. The majority of renal injuries occur as a result of blunt trauma and are amenable to conservative management. We sought to streamline the management of renal trauma in the west of Ireland. With the current restructuring of the Irish Health Service, it is important to acknowledge the role of the urologist in the management of trauma patients.

Search for lepton-flavor-violating decays of the neutral kaon.

The Fermilab KTeV experiment has searched for lepton-flavor-violating decays of the K(L) meson in three decay modes. We observe no events in the signal region for any of the modes studied, and we set the following upper limits for their branching ratios at the 90% C.L.: BR(K(L) --> pi(0) micro(+/-) e(-/+)) <7.6 x 10(-11); BR(K(L) --> pi(0)pi(0) micro(+/-) e(-/+)) <1.7 x 10(-10); BR(pi(0) --> micro(+/-) e(-/+)) <3.6 x 10(-10). This result represents a factor of 82 improvement in the branching ratio limit for K(L) --> pi(0) micro(+/-) e(-/+) and is the first reported limit for K(L) --> pi(0)pi(0) micro(+/-) e(-/+).

Determination of the parity of the neutral pion via its four-electron decay.

We present a new determination of the parity of the neutral pion via the double Dalitz decay pi0-->e+e-e+e-. Our sample, which consists of 30,511 candidate decays, was collected from KL-->pi0pi0pi0 decays in flight at the KTeV-E799 experiment at Fermi National Accelerator Laboratory. We confirm the negative pi0 parity and place a limit on scalar contributions to the pi0-->e+e-e+e- decay amplitude of less than 3.3% assuming CPT conservation. The pi0gamma*gamma* form factor is well described by a momentum-dependent model with a slope parameter fit to the final state phase-space distribution. Additionally, we have measured the branching ratio of this mode to be B(pi0-->e+e-e+e-)=(3.26+/-0.18)x10(-5).