Producer perceptions of dairy calf management, behavior, and welfare.

Approaches for raising calves vary across commercial dairy farms and relate to behavioral opportunities and animal welfare. The objectives of this study were to evaluate how US dairy producers and calf managers perceive 1) welfare implications of varying management practices (including social housing and milk allowance) and behaviors in dairy calves, and 2) aspects of the human-animal relationship in calf rearing and relationships with on-farm management and personal calf handling habits. Survey questions were primarily quantitative (e.g., Likert scales) and addressed how common calf management practices and observed calf behaviors were related to aspects of welfare, including calf health and comfort. We additionally posed questions addressing respondent habits, management protocols, and perceptions related to human-animal interaction. Responses from 93 dairy producers and calf managers were collected via digital surveys. Social housing was viewed as being generally positive for both calf comfort and health, although this view was stronger with respect to calf comfort. Respondents from farms using social housing (56%) had more positive perceptions of social housing, viewed social play as being associated with better calf comfort and health, and considered access to other calves and "freedom to express natural behavior" as being more important for calves, compared with respondents from farms not providing social housing. Providing greater milk allowances (>7.6 L/d) was viewed as being good for both calf comfort and health, although respondents from farms providing these milk allowances (59%) had more positive perceptions than those who provided lesser allowances. Abnormal oral behaviors were viewed as being associated with both poor calf comfort and health. The welfare importance of various resources which may reduce abnormal oral behaviors (including hay and brushes) was perceived more ambiguously, although respondents from farms providing these resources, compared with those who do not, generally viewed them as more preferred by calves. We observed a positive relationship between how respondents perceived the human-animal bond (i.e., that calves enjoy contact with humans) and stated personal behavior related to calf contact (frequency of contacting calves to scratch or pet them). Respondent demographics were not related to perceptions of the human-animal relationship, but respondents identifying as female described more frequent positive calf interactions. Described aspects of human-animal interactions were not related to implementation of social housing on-farm. Job satisfaction was positively related to perception of the human-animal relationship. Overall, these results suggest that most calf management personnel place a high value on calf welfare, although farms implementing social housing appear to place a greater value on subjective calf well-being and individual perceptions of animal welfare may depend on practical experience.

Molecular autopsy for fetal structural anomaly: diagnostic and clinical utility of multidisciplinary team approach.

OBJECTIVES: In the West Midlands Regional Genetic Service, cases of perinatal death with a possible genetic diagnosis are evaluated by the Perinatal Pathology Genetic Multidisciplinary Team (MDT). The MDT assessed autopsy findings and considered genomic assessments. The objective of this retrospective service evaluation was to determine the clinical utility of the MDT. This is the first evaluation since the introduction of whole genome and whole exome sequencing in routine clinical care. METHOD: The outcomes for all the perinatal MDT cases from January 2021 to December 2021 were examined. All cases received a full or partial post-mortem examination (PM) and a chromosomal microarray. Demographics, phenotype, MDT recommendations, genetic testing, diagnoses, outcomes, impact of PM and impact of genetic testing were collected from patient case notes. RESULTS: One hundred and twenty-three cases were discussed at the MDT meeting in 2021. Genetic evaluation was recommended in 84 cases and accepted in 64 cases. A range of genetic tests were requested according to indication and availability. Thirty diagnoses were identified in 29 cases from 26 unrelated families. The diagnostic yield was 24% (29/123) of all cases or 45% (29/64) of the cases with a suspected genetic diagnosis who underwent genetic testing. PM examination added clinically actionable phenotype data in 79% of cases. A genetic diagnosis enabled accurate counselling of recurrence risk and provision of appropriate follow-up, including prenatal testing and preimplantation diagnosis for patients with inherited conditions. CONCLUSIONS: Genomic testing was a clinically useful addition to (but not a substitute for) PM examination in perinatal cases associated with structural anomalies. The MDT model helped assess cases and plan appropriate follow-up. Expedited whole genome sequencing or panel-agnostic analysis were most appropriate for heterogeneous presentations. This broad approach can also expand prenatal phenotypes and detect novel disease genes and should be a priority for future research. This article is protected by copyright. All rights reserved.

Nutrient Intakes and Gastrointestinal Symptoms Among Esophagogastric Cancer Survivors up to 5 Years Post-Surgery.

A cross-sectional analysis explored nutritional intakes and gastrointestinal (GI) symptoms among esophagogastric cancer survivors up to 12, 13-36, and 37+ months post-surgery. Participants were identified from the Upper GI Cancer Registry at St James' Hospital, Ireland. The Short Nutritional Assessment Questionnaire, European Prospective Investigation of Cancer Food Frequency Questionnaire, World Cancer Research Fund/American Institute for Cancer Research (WCRF/AICR) Score, and Gastrointestinal Symptoms Rating Scale assessed malnutrition risk, nutritional intake, adherence to (secondary) cancer prevention recommendations, and GI symptoms, respectively. Most (82.5%, n33) participants (n40) were male. Mean age was 65.5 ± 9.3 years. Time post-surgery ranged from 6-62 months. Half (50.0%, n20) had a BMI in the healthy range. A quarter (27.5%, n11) were at risk of malnutrition. Intakes of meat and meat products exceeded recommendations and intakes of fruits, vegetables, and fiber were below recommendations, with no significant between-group differences. The mean WCRF/AICR score was 3.6 ± 1.1, indicating adherence to 3.6 of 7 cancer prevention recommendations. It was not significantly different between subgroups. Minor to mild GI discomfort was reported, with no significant between-group differences in symptoms. As rates of long-term survivorship continue to increase, survivors must be supported to sustain behaviors that enhance quality of life and reduce secondary cancer risk.

Subtelomeric plasticity contributes to gene family expansion in the human parasitic flatworm Schistosoma mansoni.

BACKGROUND: The genomic region that lies between the telomere and chromosome body, termed the subtelomere, is heterochromatic, repeat-rich, and frequently undergoes rearrangement. Within this region, large-scale structural changes enable gene diversification, and, as such, large multicopy gene families are often found at the subtelomere. In some parasites, genes associated with proliferation, invasion, and survival are often found in these regions, where they benefit from the subtelomere's highly plastic, rapidly changing nature. The increasing availability of complete (or near complete) parasite genomes provides an opportunity to investigate these typically poorly defined and overlooked genomic regions and potentially reveal relevant gene families necessary for the parasite's lifestyle. RESULTS: Using the latest chromosome-scale genome assembly and hallmark repeat richness observed at chromosome termini, we have identified and characterised the subtelomeres of Schistosoma mansoni, a metazoan parasitic flatworm that infects over 250 million people worldwide. Approximately 12% of the S. mansoni genome is classified as subtelomeric, and, in line with other organisms, we find these regions to be gene-poor but rich in transposable elements. We find that S. mansoni subtelomeres have undergone extensive interchromosomal recombination and that these sites disproportionately contribute to the 2.3% of the genome derived from segmental duplications. This recombination has led to the expansion of subtelomeric gene clusters containing 103 genes, including the immunomodulatory annexins and other gene families with unknown roles. The largest of these is a 49-copy plexin domain-containing protein cluster, exclusively expressed in the tegument-the tissue located at the host-parasite physical interface-of intramolluscan life stages. CONCLUSIONS: We propose that subtelomeric regions act as a genomic playground for trial-and-error of gene duplication and subsequent divergence. Owing to the importance of subtelomeric genes in other parasites, gene families implicated in this subtelomeric expansion within S. mansoni warrant further characterisation for a potential role in parasitism.

Influences of human contact following milk-feeding on nonnutritive oral behavior and rest of individual and pair-housed dairy calves during weaning.

Dairy calves are active around the time of milk-feeding and often perform nonnutritive oral behaviors, particularly during weaning. This study evaluated the interactive effects of social housing and human contact following feeding, including scratching to mimic brushing, on postfeeding nonnutritive oral behaviors and rest, during the beginning of the weaning period. We enrolled individually housed dairy heifer calves (n = 14) and pair-housed heifer calves (n = 14; 1 focal calf/pair). Human contact was provided in the form of scratching calves beneath the neck to mimic allogrooming. The human was present for 5 min, within the 15-min window following morning milk-feeding. Human contact and control days, where there was no change in the postfeeding routine, were randomized for each calf over the course of 4 consecutive days during weaning. Behavior was recorded continuously from video for 1 h following milk-feeding. Individually housed calves performed more pen-directed nonnutritive oral behavior than pair-housed calves, but provision of human contact reduced the duration of this behavior to a level that did not differ from pair-housed calves. Although human contact did not affect the duration of pen-directed nonnutritive oral behavior in pair-housed calves, cross-sucking was reduced in pair-housed calves when they received human contact. Human contact following milk-feeding reduced the total duration of all nonnutritive oral behavior (pen-directed, bedding-directed, cross-sucking, and human-directed) and increased rest with no effect of housing treatment or interaction between housing treatment and human contact. These results suggest that human contact influenced performance of nonnutritive oral behavior following milk-feeding, particularly reducing pen-directed sucking in individually housed calves, highlighting the role of restrictive environments in the expression of these behaviors in conventionally housed dairy calves.

Development of human-directed behavior in dairy calves reared individually or in pairs.

Although social contact between dairy calves has broad effects on their behavioral development, influences of calf social housing on human-animal relationships are less well understood, despite implications for longer-term calf management and welfare. We characterized human-animal interactions in 3 distinct testing contexts to examine effects of social housing on development of human-directed behavior. At birth, Holstein heifer calves were randomly assigned to individual housing (n = 17 calves) or pair housing (n = 17 calves; 1 focal calf/pair). A human approach test was performed twice in the home pen (wk 3 and 5 of life), within an open testing arena (13 × 7 m; wk 4 of life), and within group-housing pens 6 d after all calves were weaned, mingled between treatments, and moved to groups (4 calves/pen; wk 8 of life). For these tests, a human approached, and then extended their hand, over a 2 min period for home and group pen tests and a 5 min period for the arena test, and behavior was recorded from video. During preweaning human approach tests in the home pen, individually housed calves had shorter latencies to contact the human (22.4 vs. 45.1 s; individual vs. pair housing) and spent more time in contact with the human [80.5 vs. 41.1 s; standard error (SE) = 9.9; individual vs. pair housing], with similar responses between repeated tests. In the arena approach test, individually housed calves spent more time oriented toward the human (134.6 vs. 81.3 s; SE = 16.5; individual vs. pair housing), whereas pair-housed calves were more likely to perform pen-directed non-nutritive oral behavior (60 vs. 40% of calves; pair vs. individual housing), suggesting differences in interest directed toward the human compared with the novel environment. We also found that total duration of human contact was correlated between the first home pen approach test and the novel arena test, but that specific response to human approach varied between testing contexts. Effects of treatment persisted during the postweaning group pen approach test, with previously individually housed calves tending to spend more time looking toward the human (53.0 vs. 30.0 s; SE = 9.4; individual vs. pair housing) and more likely to contact the human (47 vs. 12% of calves; individual vs. pair housing). Overall, these results show persistent effects of early life social housing on human-directed behavior which may have implications for longer-term management.

Evolving fetal phenotypes and clinical impact of progressive prenatal exome sequencing pathways: cohort study.

OBJECTIVES: To determine (1) the diagnostic yield and turnaround time (TAT) of two consecutive prenatal exome sequencing (ES) pathways, (2) the evolution of the fetal phenotype and (3) the clinical impact of detecting causative pathogenic variants and incidental findings. METHODS: This was a retrospective cohort analysis of prospectively collected fetal cases that underwent trio ES in the presence of a structural anomaly and normal chromosomal microarray testing in the West Midlands Regional Genetics Laboratory, Birmingham, UK. The study included two phases: (1) between July 2018 and October 2020, the clinical pathway from the Prenatal Assessment of Genomes and Exomes (PAGE) study was adopted and involved prenatal trio ES based on a panel of 1542 development disorder genes and case selection by a multidisciplinary team; (2) between October 2020 and July 2021, prenatal trio ES investigation was based on the National Health Service (NHS) England R21 pathway, with definitive inclusion criteria and a panel of 1205 prenatally relevant genes. Deep phenotyping was performed throughout pregnancy and postnatally. RESULTS: A total of 54 cases were included. The diagnostic yield before vs after R21 pathway implementation was 28.0% (7/25) and 55.2% (16/29), respectively (P = 0.04). The respective values for mean TAT were 54.0 days (range, 14-213 days) and 14.2 days (range, 3-29 days). In cases in which a causative pathogenic variant was identified and in which the pregnancy reached the third trimester, additional anomalies were detected between the second and third trimesters in 73.3% (11/15) of cases, predominantly secondary to progressive hydropic features (3/11 (27.3%)), arthrogryposis (3/11 (27.3%)) or brain anomaly (2/11 (18.2%)). In three cases, a variant of uncertain significance was reclassified to likely pathogenic based on postnatal information. Detection of a causative pathogenic variant had a significant clinical impact in 78.3% (18/23) of cases, most frequently affecting decision-making regarding the course of the pregnancy and neonatal management (7/18 (38.9%)). CONCLUSIONS: Prenatal ES using the NHS England R21 pathway showed great promise when applied to this cohort, allowing a genetic diagnosis to be made in over half of preselected cases with a fetal structural anomaly on ultrasound. Monitoring and real-time updating of fetal phenotype and reclassification of variants based on postnatal findings is vital to increase the clinical impact that is already evident from this emerging genomic technology. © 2021 International Society of Ultrasound in Obstetrics and Gynecology.

Phenotypic and genotypic analysis of benzimidazole resistance in reciprocal genetic crosses of Haemonchus contortus.

Haemonchus contortus is arguably one of the most economically important and ubiquitous parasites of livestock globally and commonly involved in cases of anthelmintic resistance. Here, we performed reciprocal genetic crosses using susceptible (MHco3(ISE)) and multiple anthelmintic resistant (MHco18(UGA2004)) H. contortus isolates. Resultant admixed populations were designated MHco3/18 or MHco18/3, where the lead isolate reflects the origin of the females. Three independent filial generations were generated for each cross, which were subjected to bioassays, molecular approaches and population genetic analyses to investigate the phenotypic and genotypic inheritance of benzimidazole (BZ) resistance at each stage. A panel of microsatellite markers confirmed the success of the genetic cross as markers from both parents were seen in the F1 crosses. Egg hatch tests revealed a stark difference between the two F1 crosses with ED50 estimates for MHco18/3 being 9 times greater than those for MHco3/18. Resistance factors based on ED50 estimates ranged from 6 to 57 fold in the filial progeny compared to MHco3(ISE) parents. Molecular analysis of the F167Y and F200Y SNP markers associated with BZ resistance were analysed by pyrosequencing and MiSeq deep amplicon sequencing, which showed that MHco3/18.F1 and MHco18/3.F1 both had similar frequencies of the F200Y resistant allele (45.3% and 44.3%, respectively), whereas for F167Y, MHco18/3.F1 had a two-fold greater frequency of the resistant-allele compared to MHco3/18.F1 (18.2% and 8.8%, respectively). Comparison between pyrosequencing and MiSeq amplicon sequencing revealed that the allele frequencies derived from both methods were concordant at codon 200 (rc = 0.97), but were less comparable for codon 167 (rc = 0.55). The use of controlled reciprocal genetic crosses have revealed a potential difference in BZ resistance phenotype dependent on whether the resistant allele is paternally or maternally inherited. These findings provide new insight and prompt further investigation into the inheritance of BZ resistance in H. contortus.

Routine testing of close contacts of confirmed COVID-19 cases - National COVID-19 Contact Management Programme, Ireland, May to August 2020.

OBJECTIVES: The objective of this study was to inform public health practitioners who are designing, adapting and implementing testing and tracing strategies for Coronavirus disease (COVID-19) control. STUDY DESIGN: The study design is monitoring and evaluation of a national public health protection programme. METHODS: All close contacts of laboratory-confirmed cases of COVID-19 identified between the 19th May and 2nd August were included; secondary attack rates and numbers needed to test were estimated. RESULTS: Four thousand five hundred eighty six of 7272 (63%) close contacts of cases were tested with at least one test. The secondary attack rate in close contacts who were tested was 7% (95% Confidence Interval [CI]: 6.3 - 7.8%). At the 'day 0' test, 14.6% (95% CI: 11.6-17.6%) of symptomatic close contacts tested positive compared with 5.2% (95% CI: 4.4-5.9%) of asymptomatic close contacts. CONCLUSIONS: The application of additional symptom-based criteria for testing in this high-incidence population (close contacts) is of limited utility because of the low negative predictive value of absence of symptoms.

Artificial intelligence to predict clinical disability in patients with multiple sclerosis using FLAIR MRI.

PURPOSE: The purpose of this study was to create an algorithm that combines multiple machine-learning techniques to predict the expanded disability status scale (EDSS) score of patients with multiple sclerosis at two years solely based on age, sex and fluid attenuated inversion recovery (FLAIR) MRI data. MATERIALS AND METHODS: Our algorithm combined several complementary predictors: a pure deep learning predictor based on a convolutional neural network (CNN) that learns from the images, as well as classical machine-learning predictors based on random forest regressors and manifold learning trained using the location of lesion load with respect to white matter tracts. The aggregation of the predictors was done through a weighted average taking into account prediction errors for different EDSS ranges. The training dataset consisted of 971 multiple sclerosis patients from the "Observatoire français de la sclérose en plaques" (OFSEP) cohort with initial FLAIR MRI and corresponding EDSS score at two years. A test dataset (475 subjects) was provided without an EDSS score. Ten percent of the training dataset was used for validation. RESULTS: Our algorithm predicted EDSS score in patients with multiple sclerosis and achieved a MSE=2.2 with the validation dataset and a MSE=3 (mean EDSS error=1.7) with the test dataset. CONCLUSION: Our method predicts two-year clinical disability in patients with multiple sclerosis with a mean EDSS score error of 1.7, using FLAIR sequence and basic patient demographics. This supports the use of our model to predict EDSS score progression. These promising results should be further validated on an external validation cohort.

The global diversity of Haemonchus contortus is shaped by human intervention and climate.

Haemonchus contortus is a haematophagous parasitic nematode of veterinary interest. We have performed a survey of its genome-wide diversity using single-worm whole genome sequencing of 223 individuals sampled from 19 isolates spanning five continents. We find an African origin for the species, together with evidence for parasites spreading during the transatlantic slave trade and colonisation of Australia. Strong selective sweeps surrounding the ß-tubulin locus, a target of benzimidazole anthelmintic drug, are identified in independent populations. These sweeps are further supported by signals of diversifying selection enriched in genes involved in response to drugs and other anthelmintic-associated biological functions. We also identify some candidate genes that may play a role in ivermectin resistance. Finally, genetic signatures of climate-driven adaptation are described, revealing a gene acting as an epigenetic regulator and components of the dauer pathway. These results begin to define genetic adaptation to climate in a parasitic nematode.

Parental experiences of their child's vulvovaginitis: a qualitative interview study.

INTRODUCTION: Vulvovaginitis is described as a common self-limiting paediatric gynaecological condition. Parents' experiences of their child being diagnosed with this condition and subsequent treatment have not previously been described. AIM: The aim of this study was to explore parents' experiences of their child's diagnosis and management of vulvovaginitis. STUDY DESIGN: The study was conducted in the north west of England over a two-year period. Qualitative data were generated by semistructured in-depth interviews. Mothers of nine children with vulvovaginitis consented to participate. Data were analysed using thematic analysis. RESULTS: The analysis of the data resulted in four themes: trauma and uncertainty of initial symptoms, seeking a diagnosis; an uncertain journey, managing the symptoms; a process of trial and error and managing the impact; keeping it private. Parents experienced a difficult and protracted journey to their child's diagnosis and were involved in a process of trial and error to try and monitor and manage what can be a difficult ongoing condition. DISCUSSION: Clinical reports suggest that vulvovaginitis is a minor childhood condition; this is not necessarily the perceptions and experiences of parents, who can experience uncertainty and ongoing difficulty after their child's diagnosis. CONCLUSION: The diagnosis of vulvovaginitis can have a major and ongoing impact on children's and their family's lives.

Measuring the impact of oesophagectomy on physical functioning and physical activity participation: a prospective study.

BACKGROUND: Oesophagectomy remains the only curative intervention for oesophageal cancer, with defined nutritional and health-related quality of life (HR-QOL) consequences. It follows therefore that there is a significant risk of decline in physical wellbeing with oesophagectomy however this has been inadequately quantified. This study prospectively examines change in physical functioning and habitual physical activity participation, from pre-surgery through 6-months post-oesophagectomy. METHODS: Patients scheduled for oesophagectomy with curative intent were recruited. Key domains of physical functioning including exercise tolerance (six-minute walk test (6MWT)) and muscle strength (hand-grip strength), and habitual physical activity participation, including sedentary behaviour (accelerometry) were measured pre-surgery (T0) and repeated at 1-month (T1) and 6-months (T2) post-surgery. HR-QOL was measured using the EORTC-QOL C30. RESULTS: Thirty-six participants were studied (mean age 62.4 (8.8) years, n = 26 male, n = 26 transthoracic oesophagectomy). Mean 6MWT distance decreased significantly from T0 to T1 (p = 0.006) and returned to T0 levels between T1 and T2 (p < 0.001). Percentage time spent sedentary increased throughout recovery (p < 0.001) and remained significantly higher at T2 in comparison to T0 (p = 0.003). In contrast, percentage time spent engaged in either light or moderate-to-vigorous intensity activity, all reduced significantly (p < 0.001 for both) and remained significantly lower at T2 in comparison to T0 (p = 0.009 and p = 0.01 respectively). Patients reported deficits in multiple domains of HR-QOL during recovery including global health status (p = 0.04), physical functioning (p < 0.001) and role functioning (p < 0.001). Role functioning remained a clinically important 33-points lower than pre-operative values at T2. CONCLUSION: Habitual physical activity participation remains significantly impaired at 6-months post-oesophagectomy. Physical activity is a measurable and modifiable target for physical rehabilitation, which is closely aligned with patient-reported deficits in role functioning. Rehabilitation aimed at optimising physical health in oesophageal cancer survivorship is warranted.

Effect of neoadjuvant chemoradiation on preoperative pulmonary physiology, postoperative respiratory complications and quality of life in patients with oesophageal cancer.

BACKGROUND: It remains controversial whether neoadjuvant chemoradiation (nCRT) for oesophageal cancer influences operative morbidity, in particular pulmonary, and quality of life. This study combined clinical outcome data with systematic evaluation of pulmonary physiology to determine the impact of nCRT on pulmonary physiology and clinical outcomes in locally advanced oesophageal cancer. METHODS: Consecutive patients treated between 2010 and 2016 were included. Three-dimensional conformal radiation was standard, with a lung dose-volume histogram of V20 less than 25 per cent, and total radiation between 40 and 41·4 Gy. Forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC) and diffusion capacity for carbon monoxide (DLCO) were assessed at baseline and 1 month after nCRT. Radiation-induced lung injury (grade 2 or greater), comprehensive complications index (CCI) and pulmonary complications were monitored prospectively. Health-related quality of life was assessed among disease-free patients in survivorship. RESULTS: Some 228 patients were studied. Comparing pulmonary physiology values before with those after nCRT, FEV1 decreased from mean(s.d.) 96·8(17·7) to 91·5(20·4) per cent (-3·6(10·6) per cent; P < 0·001), FVC from 104·9(15·6) to 98·1(19·8) per cent (-3·2(11·9) per cent; P = 0·005) and DLCO from 97·6(20·7) to 82·2(20·4) per cent (-14·8(14·0) per cent; P < 0·001). Five patients (2·2 per cent) developed radiation-induced lung injury precluding surgical resection. Smoking (P = 0·005) and increased age (P < 0·001) independently predicted percentage change in DLCO. Carboplatin and paclitaxel with 41·4 Gy resulted in a greater DLCO decline than cisplatin and 5-fluorouracil with 40 Gy (P = 0·001). On multivariable analysis, post-treatment DLCO predicted CCI (P = 0·006), respiratory failure (P = 0·020) and reduced physical function in survivorship (P = 0·047). CONCLUSION: These data indicate that modern nCRT alters pulmonary physiology, in particular diffusion capacity, which is linked to short- and longer-term clinical consequences, highlighting a potentially modifiable index of risk.

ANTECEDENTES: El tema de si en el cáncer de esófago la quimiorradioterapia neoadyuvante (neoadjuvant chemoradiation, nCRT) repercute sobre la morbilidad postoperatoria, especialmente sobre la morbilidad pulmonar y la calidad de vida de los pacientes que sobreviven sigue siendo controvertido. Este estudio combina datos sobre resultados clínicos con una evaluación sistemática de la fisiología pulmonar para determinar el impacto de la nCRT sobre la fisiología pulmonar y los resultados clínicos en el cáncer de esófago localmente avanzado. MÉTODOS: Se incluyeron pacientes consecutivos tratados entre 2010-2016. La radioterapia conformal 3D fue la estándar, con un histograma dosis-volumen del pulmón V20 < 25% y radiación entre 40-41,4 Gy. Se evaluaron el volumen espiratorio forzado (forced expiratory volume, FEV1), la capacidad vital forzada (forced vital capacity, FVC) y la capacidad de difusión del monóxido de carbono (diffusion capacity for carbon monoxide, DLCO) al inicio y un mes tras la nCRT. La lesión pulmonar inducida por la radioterapia (EORTC grado ≥ 2), el índice de complicaciones integral (comprehensive complications index, CCI), grado de Clavien-Dindo, y complicaciones pulmonares fueron analizadas de manera prospectiva. Se evaluó la calidad de vida relacionada con la salud entre los pacientes supervivientes libres de enfermedad (EORTC QLQ-C30, OG25, OES18). RESULTADOS: Se estudiaron un total de 228 pacientes. Al comparar los valores de la fisiología pulmonar antes y después de la nCRT respectivamente, la FEV1 disminuyó de 96,8 ± 17,7% a 91,5 ± 20,4% (-3,6 ± 10,6%, P = 0,0002), la FVC de 104,9 ± 15,6 a 98,1 ± 19,8% (-3,2 ± 11,9%, P = 0,005) y la DLCO de 97,6 ± 20,7 a 82,2 ± 20,4% (-14,8 ± 14,0%, P < 0,0001). Cinco pacientes (2,2%) desarrollaron lesión pulmonar relacionada con la radioterapia impidiendo la resección quirúrgica. Los factores predictores independientes de %ΔDLCO fueron el hábito tabáquico (P = 0,005) y la edad avanzada (P < 0,001). El tratamiento con carboplatino/paclitaxel/41,4Gy determinó un mayor descenso de la DLCO en comparación con cisplatino/5-fluorouracilo/40Gy (P = 0,001). En el análisis multivariable, la DLCO tras el tratamiento fue una variable predictora de CCI (P = 0,006), fracaso respiratorio/intubación prolongada (P = 0,020) y reducción de la función física en los supervivientes (P = 0,047). CONCLUSIÓN: Estos datos indican que la moderna nCRT altera la fisiología pulmonar, especialmente la difusión pulmonar, con consecuencias clínicas a corto y largo plazo. La DLCO podría constituir un factor de riesgo potencialmente modificable.

Physical Conditions of Fast Glacier Flow: 3. Seasonally-Evolving Ice Deformation on Store Glacier, West Greenland.

Temporal variations in ice sheet flow directly impact the internal structure within ice sheets through englacial deformation. Large-scale changes in the vertical stratigraphy within ice sheets have been previously conducted on centennial to millennial timescales; however, intra-annual changes in the morphology of internal layers have yet to be explored. Over a period of 2 years, we use autonomous phase-sensitive radio-echo sounding to track the daily displacement of internal layers on Store Glacier, West Greenland, to millimeter accuracy. At a site located ∼30 km from the calving terminus, where the ice is ∼600 m thick and flows at ∼700 m/a, we measure distinct seasonal variations in vertical velocities and vertical strain rates over a 2-year period. Prior to the melt season (March-June), we observe increasingly nonlinear englacial deformation with negative vertical strain rates (i.e., strain thinning) in the upper half of the ice column of approximately -0.03 a-1, whereas the ice below thickens under vertical strain reaching up to +0.16 a-1. Early in the melt season (June-July), vertical thinning gradually ceases as the glacier increasingly thickens. During late summer to midwinter (August-February), vertical thickening occurs linearly throughout the entire ice column, with strain rates averaging 0.016 a-1. We show that these complex variations are unrelated to topographic setting and localized basal slip and hypothesize that this seasonality is driven by far-field perturbations in the glacier's force balance, in this case generated by variations in basal hydrology near the glacier's terminus and propagated tens of kilometers upstream through transient basal lubrication longitudinal coupling.

Integration of a recent infection testing algorithm into HIV surveillance in Ireland: improving HIV knowledge to target prevention.

Recent infection testing algorithms (RITA) for HIV combine serological assays with epidemiological data to determine likely recent infections, indicators of ongoing transmission. In 2016, we integrated RITA into national HIV surveillance in Ireland to better inform HIV prevention interventions. We determined the avidity index (AI) of new HIV diagnoses and linked the results with data captured in the national infectious disease reporting system. RITA classified a diagnosis as recent based on an AI < 1.5, unless epidemiological criteria (CD4 count <200 cells/mm3; viral load <400 copies/ml; the presence of AIDS-defining illness; prior antiretroviral therapy use) indicated a potential false-recent result. Of 508 diagnoses in 2016, we linked 448 (88.1%) to an avidity test result. RITA classified 12.5% of diagnoses as recent, with the highest proportion (26.3%) amongst people who inject drugs. On multivariable logistic regression recent infection was more likely with a concurrent sexually transmitted infection (aOR 2.59; 95% CI 1.04-6.45). Data were incomplete for at least one RITA criterion in 48% of cases. The study demonstrated the feasibility of integrating RITA into routine surveillance and showed some ongoing HIV transmission. To improve the interpretation of RITA, further efforts are required to improve completeness of the required epidemiological data.

Changes in gut hormones, glycaemic response and symptoms after oesophagectomy.

BACKGROUND: Oesophagectomy is associated with reduced appetite, weight loss and postprandial hypoglycaemia, the pathophysiological basis of which remains largely unexplored. This study aimed to investigate changes in enteroendocrine function after oesophagectomy. METHODS: In this prospective study, 12 consecutive patients undergoing oesophagectomy were studied before and 10 days, 6, 12 and 52 weeks after surgery. Serial plasma total fasting ghrelin, and glucagon-like peptide 1 (GLP-1), insulin and glucose release following a standard 400-kcal mixed-meal stimulus were determined. CT body composition and anthropometry were assessed, and symptom scores calculated using European Organisation for Research and Treatment of Cancer (EORTC) questionnaires. RESULTS: At 1 year, two of the 12 patients exhibited postprandial hypoglycaemia, with reductions in bodyweight (mean(s.e.m.) 17·1(3·2) per cent, P < 0·001), fat mass (21.5(2.5) kg versus 25.5(2.4) kg before surgery; P = 0·014), lean body mass (51.5(2.2) versus 54.0(1.8) kg respectively; P = 0·003) and insulin resistance (HOMA-IR: 0.84(0.17) versus 1.16(0.20); P = 0·022). Mean(s.e.m.) fasting ghrelin levels decreased from postoperative day 10, but had recovered by 1 year (preoperative: 621·5(71·7) pg/ml; 10 days: 415·1(59·80) pg/ml; 6 weeks: 309·0(42·0) pg/ml; 12 weeks: 415·8(52·1) pg/ml; 52 weeks: 547·4(83·2) pg/ml; P < 0·001) and did not predict weight loss (P = 0·198). Postprandial insulin increased progressively at 10 days, 6, 12 and 52 weeks (mean(s.e.m.) insulin AUC0-30 min : fold change 1·7(0·4), 2·0(0·4), 3·5(0·7) and 4·0(0·8) respectively; P = 0·001). Postprandial GLP-1 concentration increased from day 10 after surgery (P < 0·001), with a 3·3(1·8)-fold increase at 1 year (P < 0·001). Peak GLP-1 level was inversely associated with the postprandial glucose nadir (P = 0·041) and symptomatic neuroglycopenia (Sigstad score, P = 0·017, R2 = 0·45). GLP-1 AUC predicted loss of weight (P = 0·008, R2 = 0·52) and fat mass (P = 0·010, R2 = 0·64) at 1 year. CONCLUSION: Altered enteroendocrine physiology is associated with early satiety, weight loss and postprandial hypoglycaemia after oesophagectomy.

Effect of preoperative inspiratory muscle training on physical functioning following esophagectomy.

This study aims to examine the effect of preoperative inspiratory muscle training (IMT) on pre- and postoperative functional exercise performance in patients undergoing esophagectomy. A subcohort of patients recruited to the PREPARE randomized control trial were studied. Following evaluation of respiratory muscle function (spirometry, maximum inspiratory pressure (MIP), and inspiratory muscle endurance), postoperative mobilization (accelerometry) and postoperative physical functioning (6-minute walk test (6MWT)), participants scheduled for esophagectomy were randomly assigned to either 2 weeks of preoperative IMT or a control group. Measures were repeated on the day before surgery and postoperatively. Sixty participants (mean (standard deviation) age 64.13 (7.8) years; n = 42 male; n = 43 transthoracic esophagectomy; n = 17 transhiatial esophagectomy) were included in the final analysis (n = 28 IMT; n = 32 control). There was a significant improvement in preoperative MIP (P = 0.03) and inspiratory muscle endurance (P = 0.04); however preoperative 6MWT distance did not change. Postoperatively, control participants were more active on postoperative day (POD)1, and from POD1-POD5 (P = 0.04). Predischarge, 6MWT distance was significantly lower in the IMT group (305.61 (116.3) m) compared to controls (380.2 (47.1) m, P = 0.03). Despite an increase in preoperative respiratory muscle function, preoperative IMT does not improve pre- or postoperative physical functioning or postoperative mobilization following esophagectomy.