Social determinants of health inequalities in early phase clinical trials in Northern England.

BACKGROUND: Early phase clinical trials in Oncology represent a subspecialised area where UK patient selection is influenced by access to Experimental Cancer Medicine Centres (ECMCs). Equity of access with respect to social determinants of health (SDoH) were explored for two major ECMCs. METHODS: A retrospective cohort study including all referrals to Newcastle and Manchester ECMCs in 2021 was completed. Consent to screening or pre-screening was stratified against SDoH characteristics, including: Index of Multiple Deprivation (IMD) decile, ethnicity and distance to centre. RESULTS: 1243 patients were referred for trials. IMD quintile 1 (most deprived) patients had reduced likelihood of referral compared to expected population models (OR, 0.67; 95% CI: 0.55 to 0.80, p = <0.0001). IMD quintile 5 (least deprived) had increased likelihood of referral (OR, 1.46; 95% CI: 1.17 to 1.82, p = 0.0007). Living beyond median distance from Manchester reduced the likelihood of consenting to trials (OR, 0.72; 95% CI: 0.55 to 0.94, p = 0.015). Ethnicity data represented a White British propensity. CONCLUSIONS: Inequalities in socioeconomic and geographic factors influence referral and enrolment to early phase clinical trials in Northern England. This has implications for equity of access and generalisability of trial results internationally and warrants further study.

Effect of using 200 µg of gonadorelin at the first gonadotropin-releasing hormone of the breeding-Ovsynch on ovulatory response and pregnancies per artificial insemination in first-service lactating Holstein cows.

This study aimed to determine whether 200 µg of GnRH (gonadorelin hydrochloride) would increase ovulatory response and pregnancies per artificial insemination (P/AI) compared with 100 µg at the first GnRH of the breeding-Ovsynch of a Double-Ovsynch program (DO) in lactating Holstein cows. Weekly cohorts of primiparous (n = 719) and multiparous (n = 1,191) cows submitted to DO (GnRH, 7 d later PGF2α, 3 d later GnRH, 7 d later GnRH [G1], 7 d later PGF2α [PG1], 1 d later PGF2α, ∼32 h later GnRH [G2], and ∼16 h later timed artificial insemination [TAI]) for first service, randomly received either 100 µg or 200 µg of GnRH (gonadorelin hydrochloride) at G1 (primiparous, 64-75 DIM; multiparous, 59-70 DIM). Ovulation was determined by ultrasound 2 d after G1 (n = 1,294) and 2 d after G2 (n = 1,020). Blood samples were collected at G1 and at PG1 d to evaluate serum progesterone (P4) concentrations. Conventional (n = 314, Angus; n = 1,084, Holstein) and Holstein sexed semen (n = 276) were used. Pregnancy was diagnosed on d 32, 46, 88, and 200 post-TAI. The high dose of GnRH (200 µg) increased overall ovulatory response to G1 compared with 100 µg (81.3% vs. 65.1%), being similar between parities (primiparous, 72.2%; multiparous, 73.9%). Mean serum P4 concentrations at PG1 did not differ between treatments (100 µg: 9.59 ± 0.15 ng/mL vs. 200 µg: 9.43 ± 0.15 ng/mL). Cows with no ovulation to G1 had higher serum P4 concentrations at G1 than cows with ovulation to G1 (6.27 ± 0.19 ng/mL vs. 4.66 ± 0.07 ng/mL). At PG1, the proportion of cows with functional corpus luteum (98.7% vs. 89.7%) and serum P4 concentrations (9.68 ± 0.12 ng/mL vs. 9.14 ± 0.22 ng/mL) were greater in cows that ovulated to G1 compared with cows that did not ovulate. Also, cows that ovulated to G1 had a greater increase in serum P4 concentrations from G1 to PG1 than cows with no ovulation (5.26 ± 0.12 ng/mL vs. 3.32 ± 0.25 ng/mL). The high dose of GnRH improved overall P/AI at 32 d post-TAI in cows inseminated with conventional semen (54.6% vs. 48.2%) and tended to improve P/AI on 46 (48.8% vs. 44.9%), 88 (47.6% vs. 43.4%), and 200 (45.3% vs. 41.2%) d post-TAI. Primiparous cows inseminated with conventional semen had better P/AI than multiparous cows at d 32 (58.2% vs. 49.4%), 46 (55.1% vs. 44.4%), 88 (53.2% vs. 43.2%) and 200 (51.6% vs. 40.7%) post-TAI. Primiparous cows treated with 200 µg GnRH had lower P/AI on d 32, 46, 88, and 200 post-TAI when inseminated with sexed semen than with conventional semen. In summary, the higher dose of GnRH at G1 improved ovulatory response and P/AI at d 32 post-TAI and tended to improve P/AI at d 46, 88, and 200 post-TAI in cows inseminated with conventional semen. Moreover, the effect of treatment on P/AI in primiparous cows depended on semen type (conventional vs. sexed semen).

Symposium review: The impact of management and facilities on cow culling rates.

This symposium review examines the association between comfort and cow longevity, with a particular emphasis on optimizing resting behavior in confinement-housed systems. Housed dairy cattle demonstrate a variety of negative behavioral and physiological effects when lying time is restricted, with cows prioritizing the recovery of rest over feeding when both are deprived. There is, however, wide individual-cow variation in daily lying times, influenced by an array of cow-, housing-, and management-related factors. Cow-related factors include individual preference, parity, stage of lactation cycle, milk yield, ill health, and lameness. Lying time tends to increase with age and days in milk and during periods of ill health, whereas milk yield is negatively correlated with lying time. The effect of lameness is complicated by severity and by interactions with bedding type, which modifies the cows' ability to rise and lie down. Generally, lame cows suffer prolonged lying bouts of greater variability in length and take fewer bouts per day. Often this results in an overall increase in lying time. Thus, higher standards of cow comfort and improved cow health are not always reflected by longer lying times. Housing and management factors that influence resting behavior include the design of the resting area, access to the resting space, and the thermal microenvironment of the lying area. Provision of dry, deep loose bedding, stocking cows to allow each animal access to a resting space, allowing sufficient time to access the resting area, and providing heat abatement to reduce heat load optimize resting behavior. Because lameness and poor body condition are commonly found in culled dairy cattle, the link between cow comfort and culling is likely mediated through lameness onset and management. Optimal comfort helps prevent the onset of lameness and facilitates recovery once cows become lame, which limits the effect of lameness on feeding behavior and reduces the risk for other health-related disorders, poor reproductive performance, and early herd removal. Cow comfort cannot be assessed by measuring the duration of lying time alone. Rather, comfort is reflected by the optimization of resting behavior, providing facilities and management to allow cows to lie down when they choose to do so for as long as they need to.

Clinical evaluation of a universal adhesive in non-carious cervical lesions.

OBJECTIVES: To compare the clinical performance of a universal adhesive in class V non-carious cervical lesions (NCCLs) using two surface treatment protocols (self-etch [SfE] vs selective-enamel-etch [SelE]). MATERIAL AND METHODS: Thirty-three adults, each with ≥2 NCCLs, received one resin composite restoration utilizing a SfE universal adhesive and another utilizing the adhesive and SelE with 37% phosphoric acid. Restorations were evaluated for sensitivity, retention, marginal discoloration, marginal adaptation, and clinical acceptability through 24 months using Cochran-Mantel-Haenszel tests for stratified, ordered categorical outcomes. RESULTS: Sixty-six restorations (35 SfE, 31 SelE; 27 volunteers) were evaluated at 24 months. There were no significant differences between SfE and SelE for sensitivity, retention, marginal adaptation, or clinical acceptability. One SfE restoration was lost. Marginal adaptation was significantly worse at 24 months than baseline for SelE (P = 0.01), but not for SfE. Marginal discoloration was significantly worse for SfE (P = 0.02), but not for SelE. Sensitivity improved from baseline to 24 months for both groups (SelE P = 0.004, SfE P = 0.002). CONCLUSIONS: Twenty-four-month data indicated significantly reduced sensitivity for both groups, worse marginal discoloration for SfE, and worse marginal adaptation for SelE. No changes in retention or clinical acceptability were observed in either group. All retained restorations were clinically acceptable at 24 months. CLINICAL SIGNIFICANCE: Both self-etch and selective enamel etch techniques with a universal adhesive produced clinically acceptable results in resin composite restorations for NCCLs over 2 years.

Increased expression and phosphorylation of 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase isoforms in urinary exosomes in pre-eclampsia.

BACKGROUND: Glycolysis is altered in various kidney diseases, but little is known about glycolysis in pre-eclampsia, a multi-system disorder with major pathological effects on the kidney. Urinary exosomes provide a non-invasive alternative for studying changes in kidney metabolism. This study aims to characterise the expression and phosphorylation of isozymes of the key glycolytic regulatory protein, 6-phosphofructokinase-2-kinase/fructose-2,6-bisphosphatase (PFK-2/FBPase-2), in urinary exosomes of subjects with pre-eclampsia (PE), compared to normotensive non-pregnant (NC) and normotensive pregnant (NP) controls. METHODS: A cross-sectional study of NC (n = 19), NP (n = 23) and PE (n = 29) subjects was performed. Exosomes were isolated from urine samples by differential ultracentrifugation, and then analyzed by Western blot and densitometry for expression of PFK-2/FBPase-2 isozymes (PFKFB2, PFKFB3 and PFKFB4) and phosphorylation of PFKFB2 at residues Ser483 and Ser466 and PFKFB3 at Ser461. RESULTS: PFKFB2 expression was increased 4.7-fold in PE compared to NP (p < 0.001). PFKFB2 phosphorylation at Ser483 was increased 2.6-fold in PE compared to NP (p = 0.002). Expression of phosphorylated PFKFB2/PFKFB3 at Ser466/Ser461 was increased in PE, being present in 77.4% (95% CI 59.9-88.9%) of PE and 8.3% (95% CI 1.2-27.0%) of NP samples (p < 0.001). PFKFB3 was more commonly expressed in PE, detected in 90.3% (95% CI 74.3-97.4%) of PE and 8.3% (95% CI 1.2-27.0%) of NP samples (p < 0.001). PFKFB4 had a 7.2-fold increase in expression in PE compared to NP (p < 0.001). No significant differences between NP and NC groups were observed. CONCLUSION: Regulatory proteins that increase glycolysis are increased in the urinary exosomes of subjects with pre-eclampsia, suggesting that renal glycolysis may be increased in this condition.

Advanced schemes for underdense plasma photocathode wakefield accelerators: pathways towards ultrahigh brightness electron beams.

The 'Trojan Horse' underdense plasma photocathode scheme applied to electron beam-driven plasma wakefield acceleration has opened up a path which promises high controllability and tunability and to reach extremely good quality as regards emittance and five-dimensional beam brightness. This combination has the potential to improve the state-of-the-art in accelerator technology significantly. In this paper, we review the basic concepts of the Trojan Horse scheme and present advanced methods for tailoring both the injector laser pulses and the witness electron bunches and combine them with the Trojan Horse scheme. These new approaches will further enhance the beam qualities, such as transverse emittance and longitudinal energy spread, and may allow, for the first time, to produce ultrahigh six-dimensional brightness electron bunches, which is a necessary requirement for driving advanced radiation sources. This article is part of the Theo Murphy meeting issue 'Directions in particle beam-driven plasma wakefield acceleration'.

Quantitative and qualitative assessment of a coding system for reporting CT colonography.

AIM: To validate a coding system implemented to summarise computed tomography colonography (CTC) findings for the detection of suspected colorectal cancer (CRC) by assessing interobserver variability and also to evaluate any weaknesses through qualitative analysis. MATERIALS AND METHODS: All CTC investigations over a 6-month period (01/07/2016 to 31/12/2016) were analysed retrospectively. Each study was read initially by an advanced practitioner radiographer with a final report issued by a consultant gastrointestinal radiologist. Rates of interobserver agreement, using the kappa statistic, provided a quantitative assessment of levels of agreement. Areas of poor interobserver agreement were identified for further qualitative assessment. RESULTS: The present study included 1,321 CTC procedures and the mean age of patients was 68.4 years (range 28-96 years). Percentage agreement for colonic coding was 90% and for extra-colonic coding 47%. This corresponds to kappa scores of 0.69 (substantial agreement) and 0.22 (fair agreement), respectively. Reasons and examples of disagreement in the colonic coding are highlighted. CONCLUSIONS: High interobserver agreement was observed for C coding, suggesting it is a reproducible method of classifying intra-colonic CTC findings. Some of the difference in classifying extra-colonic findings is the perceived importance of incidental findings between readers, as well as differences in skill set; however, some themes recurred in areas of disagreement and recommendations for refining and improving the coding system are provided.

Modeled construction and operating costs of different ventilation systems for lactating dairy cows.

The objectives were to compare capital costs of building and installation of 7 ventilation systems for adult lactating dairy cow housing and evaluate the energy use and operating cost between systems. A cost model comprising stochastic and parametric modules was created to estimate the number of fans operating each day based on temperature set points; annual profiles of daily maximum, minimum, and average temperatures; ramping functions to transition between seasons; and weather data from 7 locations in the United States. Costs were described as US$ per stall per year and operating costs as US$ (kW·h) per stall per year. Building costs amoritized over 10 yr ranged from $246 to $318, where a 16-row cross-ventilated design had the minimum cost and a hybrid design incorporating elements of tunnel and natural ventilation had the maximum cost. Lowering the summer temperature set point from 22.2 to 18.0°C to potentially improve heat abatement for high-producing cows increased cost by $10.10 (101.0 kW·h). On average, an exponential ramping function for transitioning between seasons cost $55.40 (554 kW·h) compared with $61.40 (614 kW·h) for a linear function. A tunnel barn ranged from $79.40 (794 kW·h) to $212.30 (2123 kW·h), and a natural design ranged from $32.60 (326 kW·h) to $81.80 (818 kW·h) in operating costs due to fan selection alone. Cross-ventilated barns benefitted from economies of scale and had similar operating costs as naturally ventilated barns in larger facilities. On average, mechanical systems cost twice as much to operate as natural systems, and operating costs in hotter US climates were approximately double those in milder climates. Selecting a fan with low energy efficiency can increase the operating cost of any ventilation system approximately 2-fold, making fan choice a critical design element.

Thermodynamics of standing and lying behavior in lactating dairy cows in freestall and parlor holding pens during conditions of heat stress.

Heat load is a challenge for high-producing dairy cows, with adverse consequences on production, reproduction, and welfare. The objectives of this observational study in 2 commercial dairy herds were to determine the effects of environmental heat stress on standing and lying behavior, to monitor the changes in core body temperature (CBT) of cows during lying and standing bouts, and to compare changes in CBT during standing bouts in freestall pens versus standing in holding pens. High-producing cows were selected for data collection over a period of 6 d of increasing heat stress during a heat wave to which they were not acclimated. A total of 20 cows were fitted with leg accelerometers that recorded lying behavior and with vaginal temperature loggers that recorded CBT. These data were recorded at 30-s intervals. Time in the parlor holding pen was calculated from automated parlor software that recorded milking unit attachment and removal times. Mean daily temperature-humidity index in the pens increased from 68.5 to 79.0 during the 6-d trial, whereas mean daily lying time decreased from 9.5 to 6.2 h/d. The mean number of lying bouts per day remained similar at 11.1 to 12.2, but duration of lying bouts decreased from a high of 49.7 min on the coolest day to 32.8 min on the hottest day. During lying bouts, CBT increased at a mean rate of 0.50°C/h. In contrast, CBT changed at a mean rate of -0.25°C/h when standing in the freestall pens and only -0.09°C/h when standing in the milking-center holding pens. Explanatory models for the CBT at which cows ended either standing or lying bouts were derived from 6 selected lying bouts and 3 selected standing bouts for each cow on each day. The CBT at which a cow ended a lying bout was positively related to CBT and temperature-humidity index at the start of the bout, bout duration, and rate of CBT change during the bout. The CBT at which a cow ended a standing bout was negatively related to bout duration and positively related to start CBT, start temperature-humidity index, and rate of CBT change. Insights into the thermodynamics of standing and lying behavior in dairy cows during periods of heat stress provided by this study may contribute to the development of more effective strategies to mitigate heat load in dairy cattle.

Infrared thermography and behavioral biometrics associated with estrus indicators and ovulation in estrus-synchronized dairy cows housed in tiestalls.

Most Canadian dairy herds operate in tiestall housing (61%), where average estrus detection rates may be lower than 54%. The objective of this study was to evaluate infrared thermography and behavioral biometrics as indicators of estrus in dairy cows. Eighteen cyclic multiparous cows (Synch) were subjected to an estrus synchronization protocol, and 18 pregnant cows (control) received a sham protocol on the same schedule and frequency as the cyclic cow treatment. A decline in plasma concentrations of progesterone and the appearance of a dominant follicle using transrectal ultrasonography were used as indirect indicators of estrus, and the disappearance of a dominant follicle was used to confirm ovulation. All cows were monitored via visual cameras to determine the frequency of treading, drinking, neighbor interaction, tail movement, lying, and shifting behaviors. Infrared thermograms were recorded at the eye, muzzle, cheek, neck, front right foot, front left foot, rump, flank, vulva area, tail head, and withers. To evaluate the accuracy of behavioral and thermal parameters, a predefined minimum acceptable value (i.e., threshold) for estrus alerts (>0.30 Youden J index and >0.60 area under the curve) was used. Ovulation was confirmed in 14 (77.7%) out of 18 Synch cows. Eye, cheek, neck, rump, flank, vulva area, and wither thermograms exhibited higher temperatures at 48 h [cycle threshold (Δt) = +0.30 to 1.20°C] and 24 h before ovulation compared with 4 d prior to ovulation (Δt = 0.06 to 0.11°C) and during ovulation day (Δt = 0.03 to 0.32°C) in the Synch group. In addition, control cows exhibited greater treading activity per day compared with Synch cows (20.84 ± 0.39 vs. 16.35 events/5 min ± 0.34), and tail movement frequency was greater in Synch cows compared with control cows (14.84 ± 2.7 vs. 10.11 ± 4.7 events/5 min). However, within Synch cows, tail movement was the only behavior that significantly increased in frequency 2 d before ovulation (11.81 ± 1.71 events/5 min) followed by a decrease in frequency 1 d before ovulation (4.67 ± 1.05 events/5 min) compared with ovulation day (0 d; 6.10 ± 1.25 events/5 min) and during luteolysis (3 d before ovulation; 6.01 ± 1.25 events/5 min). Upon evaluation of all variables (thermograms and behavior frequencies) as estrus indicators at 48 and 24 h before ovulation, treading and tail movements before milking and 9 thermal locations satisfied the predefined minimum acceptable value for estrus alerts. This study demonstrates that fluctuations in radiated temperature measured at specific anatomical locations and the frequency of tail movements and treading behaviors can be used as a noninvasive estrus alerts in multiparous cows housed in a tiestall system.

VITamin D and OmegA-3 TriaL (VITAL) bone health ancillary study: clinical factors associated with trabecular bone score in women and men.

We investigated the association of clinical variables with TBS at baseline in the bone health sub-cohort of the VITamin D and OmegA-3 TriaL (VITAL). Lower TBS was associated with female sex, aging, BMI ≥ 25 kg/m2, SSRI use, high alcohol intake, and presence of diabetes; there was a trend towards significance between lower TBS and history of fragility fractures. INTRODUCTION: We investigated whether TBS differs by sex, race, body mass index (BMI), and other clinical variables. METHODS: The VITamin D and OmegA-3 TriaL (VITAL) is determining effects of vitamin D3 and/or omega-3 fatty acid (FA) supplements in reducing risks of cancer and cardiovascular disease. In the VITAL: Effects on Bone Structure/Architecture ancillary study, effects of these interventions on bone will be investigated. Here, we examine the associations of clinical risk factors with TBS assessments at baseline in the bone health sub-cohort, comprised of 672 participants (369 men and 303 women), mean (± SD) age 63.5 ± 6.0 years; BMI ≤ 37 kg/m2, no bisphosphonates within 2 years or other bone active medications within 1 year. RESULTS: TBS was greater in men than women (1.311 vs. 1.278, P < 0.001) and lower with elevated BMIs (P < 0.001), higher age (P = 0.004), diabetes (P = 0.008), SSRI use (P = 0.044), and high alcohol intake (P = 0.009). There was a trend for history of fragility fractures (P = 0.072), and lower TBS. TBS did not vary when analyzed by race, smoking, history of falls, and multivitamin or caffeine use. CONCLUSIONS: Lower TBS was associated with female sex, aging, BMI ≥ 25 kg/m2, SSRI use, alcohol use, and presence of diabetes; there was a trend between lower TBS and history of fragility fractures. TBS may be useful clinically to assess structural changes that may be associated with fractures among patients who are overweight or obese, those on SSRIs, or with diabetes. Ongoing follow-up studies will clarify the effects of supplemental vitamin D3 and/or FA's on TBS and other bone health measures. TRIAL REGISTRATION: NCT01747447.

An immunomagnetic separation/loop-mediated isothermal amplification method for rapid direct detection of thermotolerant Campylobacter spp. during poultry production.

AIMS: To develop a rapid test for thermotolerant Campylobacter in poultry faeces. METHODS AND RESULTS: The reported method is based on immunomagnetic separation and loop-mediated isothermal DNA amplification (IMS/LAMP). This LAMP assay is specific (demonstrated using 10 Campylobacter strains and 13 non-Campylobacter bacterial species) and sensitive (95% probability of detecting 22 genome copies). A competitive internal amplification control (IAC) has been incorporated to give unambiguous determination of negative results. Immunoseparation of Campylobacter allows direct LAMP detection from poultry boot swab samples in 90 min without enrichment or DNA purification (74% probability of detecting 10(4) CFU ml(-1) of a boot swab suspension). The analysis of 17 samples from commercial turkey farms showed 100% correlation with parallel results obtained by standard microbiological methods. CONCLUSIONS: A rapid test has been developed for direct detection of thermotolerant Campylobacter spp. in boot swab samples, thus bypassing culture enrichment or DNA extraction. The test has potential to be carried out by farm personnel on site. SIGNIFICANCE AND IMPACT OF THE STUDY: The method offers an inexpensive approach to monitor poultry infection in near real time, assisting flock management and controls to prevent introduction of Campylobacter into the food chain.

Exploring relationships between Dairy Herd Improvement monitors of performance and the Transition Cow Index in Wisconsin dairy herds.

Transition cow management has been tracked via the Transition Cow Index (TCI; AgSource Cooperative Services, Verona, WI) since 2006. Transition Cow Index was developed to measure the difference between actual and predicted milk yield at first test day to evaluate the relative success of the transition period program. This project aimed to assess TCI in relation to all commonly used Dairy Herd Improvement (DHI) metrics available through AgSource Cooperative Services. Regression analysis was used to isolate variables that were relevant to TCI, and then principal components analysis and network analysis were used to determine the relative strength and relatedness among variables. Finally, cluster analysis was used to segregate herds based on similarity of relevant variables. The DHI data were obtained from 2,131 Wisconsin dairy herds with test-day mean ≥30 cows, which were tested ≥10 times throughout the 2014 calendar year. The original list of 940 DHI variables was reduced through expert-driven selection and regression analysis to 23 variables. The K-means cluster analysis produced 5 distinct clusters. Descriptive statistics were calculated for the 23 variables per cluster grouping. Using principal components analysis, cluster analysis, and network analysis, 4 parameters were isolated as most relevant to TCI; these were energy-corrected milk, 3 measures of intramammary infection (dry cow cure rate, linear somatic cell count score in primiparous cows, and new infection rate), peak ratio, and days in milk at peak milk production. These variables together with cow and newborn calf survival measures form a group of metrics that can be used to assist in the evaluation of overall transition period performance.

Management characteristics, lameness, and body injuries of dairy cattle housed in high-performance dairy herds in Wisconsin.

The objective of this study was to benchmark the prevalence of lameness, hock and knee injuries, and neck and back injuries among high-performance, freestall-housed dairy herds in Wisconsin. A random selection of 66 herds with 200 or more cows was derived from herds that clustered with high performance in year 2011 Dairy Herd Improvement records for milk production, udder health, reproduction, and other health parameters. Herds were surveyed to collect information about management, facilities, and well-being. Well-being measures were obtained through direct observation of the high-producing mature cow group, surveying 9,690 cows in total. Total herd size averaged (mean ± standard deviation) 851±717 cows, ranging 203 to 2,966 cows, with an energy-corrected milk production of 40.1±4.4kg/cow per day. Prevalence of clinical lameness (5-point scale, locomotion score ≥3) and severe lameness (locomotion score ≥4) averaged 13.2±7.3 and 2.5±2.7%, respectively. The prevalence of all hock and knee injuries, including hair loss, swelling, and ulceration, was similar at 50.3±28.3 and 53.0±24.0%, respectively. Severe (swelling and ulceration) hock and knee injury prevalence were 12.2±15.3 and 6.2±5.5%, respectively. The prevalence of all neck injuries (including hair loss, swelling and ulceration) was 8.6±16.3%; whereas the prevalence of swollen or abraded necks was low, averaging 2.0±4.1%. Back injuries (proportion of cows with missing or abraded spinous processes, hooks, or pins) followed a similar trend with a low mean prevalence of 3.6±3.4%. Overall, physical well-being characteristics of this selection of high-producing, freestall-housed dairy herds provide evidence that lameness and injury are not inevitable consequences of the confinement housing of large numbers of dairy cattle. In particular, lameness prevalence rivals that of lower-production grazing systems. However, hock and other injury risk remains a concern that can be addressed through a choice in stall surface type. Use of deep, loose bedding yielded significant advantages over a mat or mattress type surface in terms of lameness, hock and knee injury, and proportion of cows with dirty udders (distinct demarcated to confluent plaques of manure). The performance benchmarks achieved by these herds may be used to set standards by which similarly managed herds may be judged using welfare audit tools.

Fabrication of a Feeding Obturator for Infants.

Large clefts in the lip and palate are common congenital anomalies. If the cleft palate is large enough, conventional feeding techniques may not provide proper nutrition for the infant. Feeding obturators will aid in the ability of the infant to attain suction and help the infant to feed adequately. It is necessary for the infant to have sustained weight gain prior to surgery to correct the cleft lip and/or palate. Fabrication of an infant feeding obturator is a simple technique using materials found in every dental office. An impression is made using modeling plastic impression compound. This impression is relined using irreversible hydrocolloid, and the resulting cast is used to enable a vacuum-formed obturator to be fabricated. The vacuum-formed obturator is smoothed and adjusted in the infant's mouth to ensure closure of the palate but allows pace posteriorly to allow normal breathing. The resulting obturator is well retained in the infant's mouth, allowing feeding.

Estimates of benefits and harms of prophylactic use of aspirin in the general population.

BACKGROUND: Accumulating evidence supports an effect of aspirin in reducing overall cancer incidence and mortality in the general population. We reviewed current data and assessed the benefits and harms of prophylactic use of aspirin in the general population. METHODS: The effect of aspirin for site-specific cancer incidence and mortality, cardiovascular events was collated from the most recent systematic reviews. Studies identified through systematic Medline search provided data regarding harmful effects of aspirin and baseline rates of harms like gastrointestinal bleeding and peptic ulcer. RESULTS: The effects of aspirin on cancer are not apparent until at least 3 years after the start of use, and some benefits are sustained for several years after cessation in long-term users. No differences between low and standard doses of aspirin are observed, but there were no direct comparisons. Higher doses do not appear to confer additional benefit but increase toxicities. Excess bleeding is the most important harm associated with aspirin use, and its risk and fatality rate increases with age. For average-risk individuals aged 50-65 years taking aspirin for 10 years, there would be a relative reduction of between 7% (women) and 9% (men) in the number of cancer, myocardial infarction or stroke events over a 15-year period and an overall 4% relative reduction in all deaths over a 20-year period. CONCLUSIONS: Prophylactic aspirin use for a minimum of 5 years at doses between 75 and 325 mg/day appears to have favourable benefit-harm profile; longer use is likely to have greater benefits. Further research is needed to determine the optimum dose and duration of use, to identify individuals at increased risk of bleeding, and to test effectiveness of Helicobacter pylori screening-eradication before starting aspirin prophylaxis.

Spectral Modification of Shock Accelerated Ions Using a Hydrodynamically Shaped Gas Target.

We report on reproducible shock acceleration from irradiation of a λ=10 µm CO_{2} laser on optically shaped H_{2} and He gas targets. A low energy laser prepulse (I≲10^{14} W cm^{-2}) is used to drive a blast wave inside the gas target, creating a steepened, variable density gradient. This is followed, after 25 ns, by a high intensity laser pulse (I>10^{16} W cm^{-2}) that produces an electrostatic collisionless shock. Upstream ions are accelerated for a narrow range of prepulse energies. For long density gradients (≳40 µm), broadband beams of He^{+} and H^{+} are routinely produced, while for shorter gradients (≲20 µm), quasimonoenergetic acceleration of protons is observed. These measurements indicate that the properties of the accelerating shock and the resultant ion energy distribution, in particular the production of narrow energy spread beams, is highly dependent on the plasma density profile. These findings are corroborated by 2D particle-in-cell simulations.

Trimodality therapy and definitive chemoradiotherapy for esophageal cancer: a single-center experience and review of the literature.

In the UK, the standard of care for esophageal cancer has generally combined surgery with neoadjuvant chemotherapy, with definitive chemoradiotherapy (dCRT) being reserved for certain subgroups. Chemoradiotherapy followed by surgery (trimodality therapy) has not been widely adopted. The outcomes of patients undergoing dCRT or trimodality therapy at our cancer center between 2004 and 2012 were restrospectively analyzed. Trimodality therapy was offered to selected patients of good performance status (World Health Organisation performance status 0/1), with squamous cell carcinoma or bulky adenocarcinoma. dCRT was offered to patients of good PS but with comorbidities, upper third tumors or at patient's request. Patients received four cycles of chemotherapy with a platinum agent (mostly cisplatin) and a fluoropyrimidine (mostly 5-fluorouracil) over a total of 11 weeks. Cycles 3 and 4 were given concurrently with radiotherapy: 50 Gy in 25 fractions for dCRT and 45 Gy in 25 fractions in the trimodality group. Surgery occurred 8-10 weeks following the completion of chemoradiotherapy. The cut-off length for maximum gross tumor volume length was 10 cm. One hundred two patients were included (47 received dCRT, and 55 received trimodality treatment). The majority of tumors were stage III (80.4%), and two-thirds were located in the distal esophagus (64.7%). Median follow-up was 44 months. The 2-year overall survival (OS) was 57.3% (median OS 39.7 months) for the dCRT group and 77.8% (median not reached) for the trimodality group. The 5-year OS rates were 38% and 58%, respectively. Postoperative mortality rate was low at 1.8%, and the pathological complete response rate was 23.6%. In conclusion, trimodality treatment for patients with esophageal and junctional gastroesophageal tumors offers high rates of 2-year survival, and the potential for long-term cure. dCRT is an established alternative for patients that are not fit or suitable for surgery.

First-lactation performance in cows affected by digital dermatitis during the rearing period.

The long-term effects of prepartum digital dermatitis (DD) on first-lactation performance were evaluated in a cohort of 719 pregnant heifers. All heifers were followed for a period of 6 mo until calving and classified on the basis of the number of DD events diagnosed during this period as type I, type II, or type III (no DD, one DD event, and multiple DD events, respectively). Health during the initial 60d in milk (DIM), reproductive and hoof health outcomes, and milk production were compared between the 3 heifer type groups. All logistic and linear models were adjusted for age, height, and girth circumference at enrollment, and the type of trace mineral supplementation during the prepartum period. Overall, cows experiencing DD during the rearing period showed worse production and health outcomes compared with healthy heifers during the first lactation. The percentages of assisted calvings, stillbirths, culled before 60 DIM, and diseased cows during the fresh period were numerically higher in type III cows compared with type I cows. However, none of these differences were statistically significant at the 95% confidence level. Significantly lower conception at first service [odds ratio (OR)=0.55, 95% confidence interval (95% CI): 0.33, 0.89] and increased number of days open (mean=24d, 95% CI: 5.2, 43) were observed in type III cows compared with type I cows. In relation to hoof health, a significantly increased risk of DD during the first lactation was found in type II and III cows (OR=5.16, 95% CI: 3.23, 8.29; and OR=12.5, 95% CI: 7.52, 21.1, respectively), as well as earlier occurrence of DD following calving (OR=59d, 95% CI=20, 96, and OR=74d, 95% CI: 37, 109). Compared with type I cows, statistically significant milk production losses during the initial 305 DIM of 199 and 335kg were estimated in type II and III cows, respectively. This difference was due to a greater rate of production decline (less persistence) after peak yield. No differences in monthly fat and protein percentages or somatic cell counts were observed between the heifer types. Given the long-term effects of DD on health, reproduction, and production, one of the priorities during the rearing period of dairy heifers should be efficient DD prevention and control programs. Such intensive intervention programs based on active long-term DD surveillance, mitigation of risk factors, and prompt treatment are expected to increase overall animal well-being and farm profitability by minimizing the effect of DD during the first lactation.

The effect of digital dermatitis on hoof conformation.

Digital dermatitis (DD) is the most prevalent cause of lameness of infectious origin in cattle. However, little is known about the effects of DD on hoof conformation (HC) during the clinical disease. The objectives of the present study were to (1) evaluate the changes in HC observed in feet affected with clinical DD lesions and (2) investigate the temporal relationship between DD and heel horn erosion (HHE). A longitudinal study was carried out including a cohort of 644 Holstein heifers. Digital dermatitis, HC, and presence of HHE in the rear feet of each heifer were assessed during a period of 6 mo. A total of 1,979 feet evaluations were included in the data set, of which 157 corresponded to feet presenting DD lesions >20mm [mean (SD) size of 27.2 (8.2) mm]. Age, days of pregnancy, hip height, and girth circumference were also recorded at cow level. Significant HC changes were observed in DD-affected feet. Results standardized to a period of 90d of follow-up showed an increase in heel height [mean (95% CI) 3.4 (2.5, 4.4) and 2.8 (2.0, 3.7) mm] and claw angle [0.8 (0.2, 1.4) and 1.4 (0.7, 2.0) degrees] of the medial and lateral claws, respectively. In addition, an increase in depth of the interdigital cleft [3.2 (2.7, 3.7) mm] and on debris accumulation [14% (7, 21) of feet] was also observed. Feet affected with clinical DD lesions also experienced a 46% point increase in the presence of severe HHE. In the short term, HC changes returned to normal levels when clinical cure of DD was achieved after topical treatment. In conclusion, significant HC changes occur in heifers affected by clinical DD before lameness symptoms are detected. The transformation of the heel area in feet affected by DD likely promotes the creation of a local environment that favors the persistence of the disease and the occurrence of severe HHE. To avoid further hoof damage, active surveillance and early intervention to reduce HC changes are recommended to improve DD control programs. Successful restoration of HC can be achieved upon clinical cure of DD. The long-term effects in lifetime performance of the HC changes due to DD remain to be further investigated.