Predicting postoperative complications and their impact on quality of life and functional status in older patients with breast cancer.

BACKGROUND: The percentage of older patients undergoing surgery for early-stage breast cancer has decreased over the past decade. This study aimed to develop a prediction model for postoperative complications to better inform patients about the benefits and risks of surgery, and to investigate the association between complications and functional status and quality of life (QoL). METHODS: Women aged at least 70 years who underwent surgery for Tis-3 N0 breast cancer were included between 2013 and 2018. The primary outcome was any postoperative complication within 30 days after surgery. Secondary outcomes included functional status and QoL during the first year after surgery, as assessed by the Groningen Activity Restriction Scale and the European Organisation for Research and Treatment of Cancer QLQ-C30 and QLQ-BR23 questionnaires. A prediction model was developed using multivariable logistic regression and validated externally using data from the British Bridging the Age Gap Study. Linear mixed models were used to assess QoL and functional status over time. RESULTS: The development and validation cohorts included 547 and 2727 women respectively. The prediction model consisted of five predictors (age, polypharmacy, BMI, and type of breast and axillary surgery) and performed well in internal (area under curve (AUC) 0.76, 95 per cent c.i. 0.72 to 0.80) and external (AUC 0.70, 0.68 to 0.72) validations. Functional status and QoL were not affected by postoperative complication after adjustment for confounders. CONCLUSION: This validated prediction model can be used to counsel older patients with breast cancer about the postoperative phase. Postoperative complications did not affect functional status nor QoL within the first year after surgery even after adjustment for predefined confounders.

Surgery remains the standard of care for the majority of older patients with breast cancer. The percentage of older patients with breast cancer receiving surgery is decreasing. The reason for this decline is unknown, but it might be due to fear of complications. To better inform patients about the benefits and risks of surgery, the aim of this study was to develop a prediction model for complications after surgery. Another important aspect, especially for older adults with breast cancer, is quality of life, functional capacity, and ability to carry out daily tasks (functional status) after therapy. This study showed that quality of life and functional status did not decline after breast surgery, irrespective of the occurrence of postoperative complications.

Bridging the age gap in breast cancer: impact of omission of breast cancer surgery in older women with oestrogen receptor-positive early breast cancer on quality-of-life outcomes.

BACKGROUND: Primary endocrine therapy may be an alternative treatment for less fit women with oestrogen receptor (ER)-positive breast cancer. This study compared quality-of-life (QoL) outcomes in older women treated with surgery or primary endocrine therapy. METHODS: This was a multicentre, prospective, observational cohort study of surgery or primary endocrine therapy in women aged over 70 years with operable breast cancer. QoL was assessed using European Organisation for Research and Treatment of cancer QoL questionnaires QLQ-C30, -BR23, and -ELD14, and the EuroQol Five Dimensions 5L score at baseline, 6 weeks, and 6, 12, 18, and 24 months. Propensity score matching was used to adjust for baseline variation in health, fitness, and tumour stage. RESULTS: The study recruited 3416 women (median age 77 (range 69-102) years) from 56 breast units. Of these, 2979 (87.2 per cent) had ER-positive breast cancer; 2354 women had surgery and 500 received primary endocrine therapy (125 were excluded from analysis due to inadequate data or non-standard therapy). Median follow-up was 52 months. The primary endocrine therapy group was older and less fit. Baseline QoL differed between the groups; the mean(s.d.) QLQ-C30 global health status score was 66.2(21.1) in patients who received primary endocrine therapy versus 77.1(17.8) among those who had surgery plus endocrine therapy. In the unmatched analysis, changes in QoL between 6 weeks and baseline were noted in several domains, but by 24 months most scores had returned to baseline levels. In the matched analysis, major surgery (mastectomy or axillary clearance) had a more pronounced adverse impact than primary endocrine therapy in several domains. CONCLUSION: Adverse effects on QoL are seen in the first few months after surgery, but by 24 months these have largely resolved. Women considering surgery should be informed of these effects.

Breast cancer surgery in older women: outcomes of the Bridging Age Gap in Breast Cancer study.

BACKGROUND: Breast cancer surgery in older women is variable and sometimes non-standard owing to concerns about morbidity. Bridging the Age Gap in Breast Cancer is a prospective multicentre cohort study aiming to determine factors influencing treatment selection and outcomes from surgery for older patients with breast cancer. METHODS: Women aged at least 70 years with operable breast cancer were recruited from 57 UK breast units between 2013 and 2018. Associations between patient and tumour characteristics and type of surgery in the breast and axilla were evaluated using univariable and multivariable analyses. Oncological outcomes, adverse events and quality-of-life (QoL) outcomes were monitored for 2 years. RESULTS: Among 3375 women recruited, surgery was performed in 2816 patients, of whom 24 with inadequate data were excluded. Sixty-two women had bilateral tumours, giving a total of 2854 surgical events. Median age was 76 (range 70-95) years. Breast surgery comprised mastectomy in 1138 and breast-conserving surgery in 1716 procedures. Axillary surgery comprised axillary lymph node dissection in 575 and sentinel node biopsy in 2203; 76 had no axillary surgery. Age, frailty, dementia and co-morbidities were predictors of mastectomy (multivariable odds ratio (OR) for age 1·06, 95 per cent c.i. 1·05 to 1·08). Age, frailty and co-morbidity were significant predictors of no axillary surgery (OR for age 0·91, 0·87 to 0·96). The rate of adverse events was moderate (551 of 2854, 19·3 per cent), with no 30-day mortality. Long-term QoL and functional independence were adversely affected by surgery. CONCLUSION: Breast cancer surgery is safe in women aged 70 years or more, with serious adverse events being rare and no mortality. Age, ill health and frailty all influence surgical decision-making. Surgery has a negative impact on QoL and independence, which must be considered when counselling patients about choices.

ANTECEDENTES: La cirugía del cáncer de mama en mujeres mayores es variable y, a veces, no estandarizada debido a las reservas que origina la morbilidad quirúrgica. Bridging the Age Gap in Breast Cancer es un estudio de cohortes, prospectivo, multicéntrico cuyo objetivo fue determinar los factores que influyen en la selección del tratamiento y en los resultados de la cirugía en pacientes mayores con cáncer de mama. MÉTODOS: Se reclutaron mujeres de > 70 años de edad con cáncer de mama operable atendidas en 56 unidades de mama del Reino Unido entre 2013-2018. Los datos sobre las características de la paciente y del tumor se correlacionaron con el tipo de cirugía en la mama y en la axila mediante análisis univariable y multivariable. Se controlaron los resultados oncológicos, los eventos adversos y los resultados en cuanto a la calidad de vida durante 2 años. RESULTADOS: De 3.375 mujeres reclutadas, se realizó una intervención quirúrgica en 2.816 pacientes. Hubo 62 tumores bilaterales, por lo que se analizan 2.854 procedimientos. La mediana de edad fue de 76 años (rango 70-95). En 1.138 pacientes se realizó una mastectomía y en 1.798 cirugía conservadora de la mama. En cuanto a la cirugía de la axila, en 575 pacientes se realizó una linfadenectomía, en 2.203 una biopsia de ganglio centinela y en 76 no se realizó ningún procedimiento. Los factores predictores de mastectomía fueron la edad, la fragilidad, la demencia y las comorbilidades (riesgo relativo, RR 1,06; i.c. del 95% 1,05-1,08), mientras que para la cirugía axilar los factores predictores fueron la fragilidad y las comorbilidades (RR 0,91; i.c. del 95% 0,87-0,96). La tasa de efectos adversos fue moderada (551/2854; 19,3%), sin mortalidad a los 30 días. La calidad de vida a largo plazo y la independencia funcional se vieron negativamente afectadas por la cirugía. CONCLUSIÓN: La cirugía de cáncer de mama es segura, con escasos efectos adversos graves y sin mortalidad. La edad, las comorbilidades y la fragilidad tienen impacto en la toma de decisiones quirúrgicas. La cirugía tiene una repercusión negativa en la calidad de vida e independencia funcional, hechos que deben ser tenidos en cuenta al aconsejar a las pacientes sobre las opciones terapéuticas.

Bridging the Age Gap: a prognostic model that predicts survival and aids in primary treatment decisions for older women with oestrogen receptor-positive early breast cancer.

BACKGROUND: A prognostic model was developed and validated using cancer registry data. This underpins an online decision support tool, informing primary treatment choice for women aged 70 years or older with hormone receptor-positive early breast cancer. METHODS: Data from women diagnosed between 2002 and 2010 in the English Northern and Yorkshire and West Midlands regions were used to develop the model. Primary treatment options of surgery with adjuvant endocrine therapy or primary endocrine therapy were compared. Models predicting the hazard of breast cancer-specific mortality and hazard of other-cause mortality were combined to derive survival probabilities. The model was validated externally using data from the Eastern Cancer Registration and Information Centre. RESULTS: The model was developed using data from 23 842 women, and validated externally on a data set from 14 526 patients. The overall model calibration was good. At 2 and 5 years, predicted mortality from breast cancer and other causes differed from the observed rate by less than 1 per cent. At 5 years, there were slight overpredictions in breast cancer mortality (2629 predicted versus 2556 observed deaths; P = 0·142) and mortality from all causes (6399 versus 6320 respectively; P = 0·583). The discrepancy varied between subgroups. Model discrimination was 0·75 or above for all mortality measures. CONCLUSION: A prognostic model for older women with oestrogen receptor-positive early breast cancer was developed and validated in the present study. This forms a basis for an online decision support tool (https://agegap.shef.ac.uk/).

ANTECEDENTES: Se ha desarrollado y validado un modelo pronóstico utilizando datos del registro de cáncer. Ello ha permitido ofrecer una herramienta online para facilitar la toma de decisiones respecto a la elección del tratamiento inicial en mujeres mayores de 70 años con cáncer de mama precoz y receptores de hormonas positivos. MÉTODOS: Se incluyeron un total de 23.842 mujeres, diagnosticadas entre 2002 y 2010 en las regiones del Norte, Yorkshire y West Midlands inglesas que cumplieron con los criterios de inclusión. Se compararon dos opciones de tratamiento: cirugía primaria asociada a tratamiento endocrino adyuvante o tratamiento primario endocrino. Para estimar la probabilidad de supervivencia se combinaron modelos predictivos para el riesgo de mortalidad específica por cáncer de mama y para el riesgo de mortalidad por otras causas. Se realizó una validación externa con datos del Eastern Cancer Registration and Information Center (n = 14.526). RESULTADOS: La calibración global del modelo fue buena. A los 2 y 5 años, la mortalidad anticipada por cáncer de mama y por otras causas difería de la observada en menos del 1%. A los 5 años, hubo una ligera sobrevaloración de la predicción de mortalidad por cáncer de mama (prevista versus real: 2.629 versus 2.556, P = 0,78) y de la mortalidad por todas las causas (6.399 versus 6.320, P = 0,14). Esta discrepancia varió entre subgrupos. La capacidad discriminativa del modelo fue del 0,75 o superior para todas las medidas de mortalidad. CONCLUSIÓN: En este estudio, se desarrolló y validó un modelo pronóstico para mujeres mayores con cáncer de mama precoz positivo para receptores de estrógenos. Esta herramienta que facilita la toma de decisiones está disponible online (https://agegap.shef.ac.uk/).

Genome-wide association study to identify genetic loci associated with gastrointestinal nematode resistance in Katahdin sheep.

Resistance to gastrointestinal nematodes has previously been shown to be a moderately heritable trait in some breeds of sheep, but the mechanisms of resistance are not well understood. Selection for resistance currently relies upon faecal egg counts (FEC), blood packed cell volumes and FAMACHA visual indicator scores of anaemia. Identifying genomic markers associated with disease resistance would potentially improve the selection process and provide a more reliable means of classifying and understanding the biology behind resistant and susceptible sheep. A GWAS was conducted to identify possible genetic loci associated with resistance to Haemonchus contortus in Katahdin sheep. Forty animals were selected from the top and bottom 10% of estimated breeding values for FEC from a total pool of 641 sires and ram lambs. Samples were genotyped using Applied Biosystems™ Axiom™ Ovine Genotyping Array (50K) consisting of 51 572 SNPs. Following quality control, 46 268 SNPs were included in subsequent analyses. Analyses were conducted using a linear regression model in plink v1.90 and a single-locus mixed model in snp and variation suite. Genome-wide significance was determined by a Bonferroni correction for multiple testing. Using linear regression, loci on chromosomes 2, 3, 16, 23 and 24 were significantly associated at the genome level with FEC estimated breeding values, and we identified a region on chromosome 2 that was significant using both statistical analyses. We suggest a potential role for the gene DIS3L2 for gastrointestinal nematode resistance in Katahdin sheep, although further research is needed to validate these findings.

Omission of surgery in older women with early breast cancer has an adverse impact on breast cancer-specific survival.

BACKGROUND: Primary endocrine therapy is used as an alternative to surgery in up to 40 per cent of women with early breast cancer aged over 70 years in the UK. This study investigated the impact of surgery versus primary endocrine therapy on breast cancer-specific survival (BCSS) in older women. METHODS: Cancer registration data for 2002-2010 were obtained from two English regions. A retrospective analysis was performed for women with oestrogen receptor (ER)-positive disease, using statistical modelling to show the effect of treatment (surgery or primary endocrine therapy) and age and health status on BCSS. Missing data were handled using multiple imputation. RESULTS: Cancer registration data on 23 961 women were retrieved. After data preprocessing, 18 730 of 23 849 women (78·5 per cent) were identified as having ER-positive disease; of these, 10 087 (53·9 per cent) had surgery and 8643 (46·1 per cent) had primary endocrine therapy. BCSS was worse in the primary endocrine therapy group than in the surgical group (5-year BCSS rate 69·4 and 89·9 per cent respectively). This was true for all strata considered, although the difference was less in the cohort with the greatest degree of co-morbidity. For older, frailer patients the hazard of breast cancer death had less relative impact on overall survival. CONCLUSION: BCSS in older women with ER-positive disease is worse if surgery is omitted. This treatment choice may contribute to inferior cancer outcomes. Selection for surgery on the basis of predicted life expectancy may permit choice of women for whom surgery confers little benefit.

Examining the variation in consent in general surgery.

INTRODUCTION: Consent is a fundamental aspect of surgery and expectations around the consent process have changed following the Montgomery vs Lanarkshire Health Board (2015) court ruling. This study aimed to identify trends in litigation pertaining to consent, explore variation in how consent is practised among general surgeons and identify potential causes of this variation. METHODS: This mixed-methods study examined temporal variation in litigation rates relating to consent (between 2011 and 2020), using data obtained from National Health Service (NHS) Resolutions. Semi-structured clinician interviews were then conducted to gain qualitative data regarding how general surgeons take consent, their ideologies and their outlook on the recent legal changes. The quantitative component included a questionnaire survey aiming to explore these issues with a larger population to improve the generalisability of the findings. RESULTS: NHS Resolutions litigation data showed a significant increase in litigation pertaining to consent following the 2015 health board ruling. The interviews demonstrated considerable variation in how surgeons approach consent. This was corroborated by the survey, which illustrated considerable variation in how consent is documented when different surgeons are presented with the same case vignette. CONCLUSION: A clear increase in litigation relating to consent was seen in the post-Montgomery era, which may be due to legal precedent being established and increased awareness of these issues. Findings from this study demonstrate variability in the information patients receive. In some cases, consent practices did not adequately meet current regulations and therefore are susceptible to potential litigation. This study identifies areas for improvement in the practice of consent.

Examining the barriers faced by female surgical trainees: a qualitative study.

INTRODUCTION: Today, women make up 56% of medical students, yet just 13% of surgical consultants - a number that has remained static since 2013. This qualitative study explored some of the barriers to female success in modern surgery. METHODS: Semistructured qualitative interviews were undertaken primarily with female surgical trainees to determine the barriers they face. Male trainees and training programme directors (TPDs) were also interviewed for triangulation. RESULTS: 20 interviews were performed (16 female trainees, 3 male trainees, and 1 TPD) between October 2019 and March 2020. Family pressures and becoming a mother were significant barriers for women training in surgery - a barrier that did not apply to male trainees who were fathers, often resulting in women choosing to train less than full time (LTFT). Unfortunately LTFT training presents further obstacles for female trainees. The set-up of the national training programme in surgery provides many non-gender-specific barriers, chiefly moving hospital every 6 months causing disrupted training and long commutes, disproportionately affecting females with child care responsibilities. Sexism and discrimination are still common, both from colleagues and patients. Many participants perceived inherent differences between genders in communication and methods for coping with stress. CONCLUSION: Greater gender equality in surgery may be achieved by changes in the structure and organisation of training to reduce the tension between the professional role and the predominantly female-led role of raising children. Better equality and diversity training and awareness at all levels in surgery may help to mitigate some of the conscious and unconscious bias that still exists.

Abdominal trauma in primary blast injury.

BACKGROUND: Blast injury is uncommon, and remains poorly understood by most clinicians outside regions of active warfare. Primary blast injury (PBI) results from the interaction of the blast wave with the body, and typically affects gas-containing organs such as the ear, lungs and gastrointestinal tract. This review investigates the mechanisms and injuries sustained to the abdomen following blast exposure. METHODS: MEDLINE was searched using the keywords 'primary blast injury', 'abdominal blast' and 'abdominal blast injury' to identify English language reports of abdominal PBI. Clinical reports providing sufficient data were used to calculate the incidence of abdominal PBI in hospitalized survivors of air blast, and in open- and enclosed-space detonations. RESULTS: Sixty-one articles were identified that primarily reported clinical or experimental abdominal PBI. Nine clinical reports provided sufficient data to calculate an incidence of abdominal PBI; 31 (3·0 per cent) of 1040 hospitalized survivors of air blast suffered abdominal PBI, the incidence ranging from 1·3 to 33 per cent. The incidence for open- and enclosed-space detonations was 5·6 and 6·7 per cent respectively. The terminal ileum and caecum were the most commonly affected organs. Surgical management of abdominal PBI is similar to that of abdominal trauma of other causes. CONCLUSION: Abdominal PBI is uncommon but has the potential for significant mortality and morbidity, which may present many days after blast exposure. It is commoner after blast in enclosed spaces and under water.

Hepatitis B virus transgenic mouse model of chronic liver disease.

A model for hepatitis B virus-associated chronic liver disease has been made using cloned hepatitis B virus DNA as a transgene in a severe combined immunodeficient host. These mice consistently support virus gene expression and replication. After adoptive transfer of unprimed, syngeneic splenocytes, these mice cleared virus from liver and serum, and developed chronic liver disease. This model will permit identification of the host and virus contributions to chronic liver disease in the absence of tolerance.

Tubulin constancy during morphological differentiation of mouse neuroblastoma cells.

Clonal cell lines N18 and N103 of the mouse neuroblastoma C1300 possess an undifferentiated neuroblast morphology under optimal growth conditions; however, when deprived of serum, N18 can be induced to extend long neurites. Although initial neurite outgrowth is rapid, very long fibers are found only after several days. Both initial outgrowths and established neurites contain microtubules; however, the number and density of these polymerized tubules increase markedly during this time. Optimum conditions have been established for assessing the colchicine-binding activity of neuroblastoma sonicates. A time-decay colchicine-binding assay was used to make a comparative study of the tubulin content of both undifferentiated and differentiated N18 as well as the nondifferentiating N103 and the rat glioma C6. Both morphologies of clone N18 possessed similar concentrations of tubulin (130-140 pmol/10(6) cells). Although cells of clone N103 contain 20% less tubulin than N18 cells, this is considerably more tubulin than is present in the glioma C6 (30 pmol/10(6) cells) which has a similar generation time. Quantitative densitometry of neuroblastoma extracts electrophoresed on SDS-polyacrylamide gels confirmed the constancy of tubulin. Radiolabeled proteins from neuroblastoma cells subjected to both growth conditions show that neurite outgrowth does not create a disproportionate demand for tubulin synthesis. Thus, the morphological differentiation of neuroblastoma cells probably reflects the regulation of tubulin storage and microtubule polymerization.

Quantitation of cytoplasmic tubulin by radioimmunoassay.

A radioimmunoassay has been developed for the quantitation of crytoplasmic tubulin. It measures tubulin between 20 and 1500 nanograms and does so independently of decay in colchicine-binding activity. In addition, the state of tubulin as subunit or polymer does not alter the measurement.

Oesophageal stenting in a district general hospital.

BACKGROUND: Oesophageal carcinoma is the ninth most common malignancy in the UK with five year survival rate of only 8%. Most patients with dysphagia present at an advanced stage. Endoscopic stent insertion is a valid method of palliation. We present the outcomes of patients stented at a district general hospital. METHOD: This is a retrospective study of patients presenting to a district general hospital with inoperable oesophageal obstruction resulting in stent insertion from December 2000 to September 2006. Case notes were reviewed for demographics, diagnosis, treatment, complication and outcome. RESULTS: Fifty-seven patients were stented endoscopically by a single surgeon during the study period for incurable oesophageal obstruction. Forty were male and 17 female (mean age 71.9 range 39-92). Most common causes were advanced adenocarcinoma (34; 60%) and squamous cell carcinoma (16; 28%). Other rarer causes were benign stricture of the oesophagus, lung carcinoma, non-Hodgkin's lymphoma and salivary gland tumour. Of the 50 patients with oesophageal carcinoma, strictures were in the lower third (in 68%), middle third (in 30%) and proximal third (in 2%). Twenty-four (42%) patients developed a complication, including overgrowth (14; 25%), migration (8; 14%), tracheo-oesophageal fistula (2; 4%) and perforation (1; 2%). There was an overall improvement in dysphagia in 41 (72%). CONCLUSION: Endoscopic stenting for advanced oesophageal obstruction is a well-tolerated procedure, which is acceptable to patients. Despite a significant complication rate, it allows the relief of dysphagia in most patients and therefore should be considered for all patients in this category.

Adjuvant Chemotherapy for Breast Cancer in Older Women: An Analysis of Retrospective English Cancer Registration Data.

AIMS: Adjuvant chemotherapy is recommended as a treatment for women with high recurrence risk early breast cancer. Older women are less likely to receive chemotherapy than younger women. This study investigated the impact of chemotherapy on breast cancer-specific survival in women aged 70 + years using English registry data. MATERIALS AND METHODS: Cancer registration data were obtained from two English regions from 2002 to 2012 (n = 29 728). The impact of patient-level characteristics on the probability of receiving adjuvant chemotherapy was explored using logistic regression. Survival modelling was undertaken to show the effect of chemotherapy and age/health status on breast cancer-specific survival. Missing data were handled using multiple imputation. RESULTS: In total, 11 735 surgically treated early breast cancer patients were identified. Use of adjuvant chemotherapy has increased over time. Younger age at diagnosis, increased nodal involvement, tumour size and grade, oestrogen receptor-negative or human epidermal growth factor receptor 2-positive disease were all associated with increased probability of receiving chemotherapy. Chemotherapy was associated with a significant reduction in the hazard of breast cancer-specific mortality in women with high risk cancer, after adjusting for patient-level characteristics (hazard ratio 0.74, 95% confidence interval 0.67-0.81). DISCUSSION: Chemotherapy is associated with an improved breast cancer-specific survival in older women with early breast cancer at high risk of recurrence . Lower rates of chemotherapy use in older women may, therefore, contribute to inferior cancer outcomes. Decisions on potential benefits for individual patients should be made on the basis of life expectancy, treatment tolerance and patient preference.

Genetic parameters for fecal egg counts and their relationship with body weights in Katahdin lambs.

Reliance on anthelmintic drugs to control internal parasites in sheep is no longer sustainable because of the development of resistance to these drugs in parasite populations. Genetic selection may offer an alternative long-term solution, as differences in parasite resistance exist both within and among sheep breeds. However, selection for parasite resistance may have correlated effects on other production traits. The objectives of this study were to estimate genetic parameters for weaning (WFEC) and postweaning (PWFEC) fecal egg counts (FEC) and assess their relationship with birth (BWT), weaning (WWT), and postweaning (PWWT) BW in Katahdin lambs. The study used WFEC (n = 2,537), PWFEC (n = 3.421), BWT (n = 12,869), WWT (n = 10,961), and PWWT (n = 7,812) from 12,869 lambs measured between 2003 and 2015 in 13 flocks enrolled in the U.S. National Sheep Improvement Program. Animal and sire models were fitted to the data using the ASReml statistical package. Records were corrected for fixed effects of dam age, joint effect of type of birth and rearing, and management group (defined by joint effects of flock, sex, and birth year and season); lamb age in days at each measurement time was fitted as a covariate. Maternal additive and maternal permanent environmental effects were not significant (P > 0.05), but litter effects influenced (P < 0.01) both WFEC and PWFEC. Heritability estimates ranged from 0.18 to 0.26 for WFEC and 0.23 to 0.46 for PWFEC, depending on the model used. Heritability estimates from sire models were higher than estimates from animal models. Direct additive, litter, residual, and phenotypic correlations between WFEC and PWFEC were 0.82, 0.25, 0.15, and 0.29, respectively. Bivariate analyses revealed low to moderate correlations between BW and FEC. Moderate heritabilities for FEC in this study indicated that genetic progress for this trait can be achieved in Katahdin lambs and that selection for low FEC should have little or no effect on BW.

Variance components for direct and maternal effects on body weights of Katahdin lambs.

The aim of this study was to estimate genetic parameters for BW in Katahdin lambs. Six animal models were used to study direct and maternal effects on birth weight (BWT), weaning weight (WWT), and postweaning weight (PWWT) using 41,066 BWT, 33,980 WWT, and 22,793 PWWT records collected over 17 yr in 100 flocks. Models included fixed effects of management group, dam age, type of birth (for BWT) or birth and rearing (for WWT and PWWT), and lamb age at weighing (fitted as a covariate for WWT and PWWT; all < 0.05). Variance components for random effects were estimated in sequentially more complex models and tested for significance with likelihood-ratio tests. A model that fitted only an additive animal effect overestimated additive variance for all BW, resulting in larger estimates of direct heritability than models that included maternal effects. Maternal effects explained variation ( < 0.05) in all BW. Heritability estimates for optimal models were 0.15 ± 0.01 for BWT, 0.18 ± 0.02 for WWT, and 0.20 ± 0.02 for PWWT. Estimates of maternal heritabilities were 0.14 for BWT, 0.10 for WWT, and 0.06 for PWWT, with SE = 0.01. Permanent environmental maternal effects explained 4 to 6% (±1%) of total phenotypic variances for these BW. Litter effects included temporary environmental effects common to littermates and a proportion of the dominance genetic variance and accounted for 16 to 19% (±1%) of phenotypic variance. Correlations between additive direct and maternal genetic effects were -0.14 for BWT, -0.23 for WWT, and -0.04 for PWWT but differed from 0 ( < 0.05) only for WWT. The total heritability predicted the total response in direct and maternal genetic effects from mass selection and was 0.23 for BWT, 0.20 for WWT, and 0.23 for PWWT. Direct and maternal additive, maternal permanent environmental, residual, and phenotypic correlations between BWT and WWT were 0.53 ± 0.05, 0.58 ± 0.06, 0.51 ± 0.06, 0.39 ± 0.01, and 0.44 ± 0.01, respectively; those between BWT and PWWT were 0.45 ± 0.06, 0.58 ± 0.08, 0.36 ± 0.08, 0.33 ± 0.01, and 0.37 ± 0.01 respectively; and those between WWT and PWWT were 0.85, 0.99, 0.92, 0.77, and 0.81, respectively, with SE ≤ 0.02. Therefore, both direct and maternal effects had an important impact on BW in Katahdin lambs. Models that included both additive and permanent environmental maternal effects as well as a temporary environmental litter effect should result in more accurate estimates of breeding values and better selection decisions.

Association between FAMACHA scores and fecal egg counts in Katahdin lambs.

The FAMACHA system was introduced to the U.S. just over 10 yr ago to allow selective deworming of lambs with anemia associated with and retard the development of anthelmintic resistance. The FAMACHA system was initially developed as a predictor of packed cell volume (PCV), but correlations between FAMACHA and fecal egg counts (FEC) have also been reported. It is important to understand factors that influence FAMACHA scores among farms to improve management of gastrointestinal nematodes. The objectives of this study were therefore to quantify associations between FAMACHA scores, FEC, BW, and age in Katahdin lambs at 2 different measurement times in 8 flocks in the eastern U.S., and to assess consistency of relationships between FAMACHA and FEC among flocks. Data came from 1,644 Katahdin lambs from 7 flocks sampled at approximately 90 d of age, and 1,295 lambs from 6 flocks sampled at approximately 120 d of age over a 5 yr period. Residual correlations among log-transformed FEC (LFEC), FAMACHA scores, BW, and lamb ages at each measurement time were determined. Repeatability of each variable was also determined as residual correlations among repeated measures. At both 90 and 120 d of age, correlations of FAMACHA scores with LFEC and BW were significant ( < 0.001), but numerically modest (0.25 and -0.16, respectively at 90 d; 0.31 and -0.16, respectively at 120 d), demonstrating that higher FAMACHA scores were associated with higher FEC and more likely to be observed in lighter lambs. A small negative correlation was observed between FAMACHA score and lamb age ( = -0.05, = 0.05, 90 d; = -0.11, < 0.001, 120 d) indicating that younger lambs were more likely to have elevated FAMACHA scores. Thus, younger and lighter lambs will likely be more susceptible to parasitism and may need to be managed more diligently than older or heavier lambs. In addition, FAMACHA scores have potential to improve breeding value estimates in programs designed to genetically improve parasite resistance.

Factors affecting fecal egg counts in periparturient Katahdin ewes and their lambs.

Selection for low fecal egg counts (FEC) can be used to genetically enhance resistance to gastrointestinal nematode parasites in growing lambs, thereby reducing the frequency of use of anthelmintics, facilitating marketing of organic lamb, and reducing the risk of development of anthelmintic resistance by the parasite. Recording of FEC in lambs has, therefore, been incorporated into several national sheep genetic evaluation programs. Ewes in late gestation and early lactation are also vulnerable to parasite infection and commonly experience a periparturient rise in FEC. This study was designed to assess factors associated with the periparturient rise in FEC in Katahdin ewes and associated changes in FEC in their lambs. Data came from 1,487 lambings by 931 Katahdin ewes from 11 farms in the Eastern United States. Fecal egg counts were measured in ewes at approximately 0, 30, and 60 d postpartum and in their lambs at approximately 60, 90, and 120 d of age. Approximately 1,400 lambs were evaluated at each measurement age. Data were analyzed separately for ewes and lambs and also initially analyzed separately for each measurement time. Repeated-measures analyses were then used to evaluate responses across measurement times. In ewes, FEC peaked at approximately 28 d postpartum, and we concluded that informative periparturient FEC could be obtained from 1 wk before until approximately 5 wk after lambing. Yearling ewes had higher FEC than adult ewes ( < 0.01), and ewes that nursed twin or triplet lambs had higher FEC than ewes that nursed single lambs ( < 0.01). In lambs, FEC increased through approximately 120 d of age. Lambs from yearling ewes and lambs nursed in larger litters were, like their dams, at greater risk of parasitism ( < 0.05). Ewes and lambs in these groups would benefit from enhanced monitoring of parasite loads at lambing and in early lactation. Correlations () between FEC in lambs at 90 d of age and FEC in ewes at 0, 30, and 60 d postpartum of 0.05 to 0.09 ( ≤ 0.05) support the presence of a genetic relationship between these 2 indicators of parasite resistance.

What influences healthcare professionals' treatment preferences for older women with operable breast cancer? An application of the discrete choice experiment.

INTRODUCTION: Primary endocrine therapy (PET) is used variably in the UK as an alternative to surgery for older women with operable breast cancer. Guidelines state that only patients with "significant comorbidity" or "reduced life expectancy" should be treated this way and age should not be a factor. METHODS: A Discrete Choice Experiment (DCE) was used to determine the impact of key variables (patient age, comorbidity, cognition, functional status, cancer stage, cancer biology) on healthcare professionals' (HCP) treatment preferences for operable breast cancer among older women. Multinomial logistic regression was used to identify associations. RESULTS: 40% (258/641) of questionnaires were returned. Five variables (age, co-morbidity, cognition, functional status and cancer size) independently demonstrated a significant association with treatment preference (p < 0.05). Functional status was omitted from the multivariable model due to collinearity, with all other variables correlating with a preference for operative treatment over no preference (p < 0.05). Only co-morbidity, cognition and cancer size correlated with a preference for PET over no preference (p < 0.05). CONCLUSION: The majority of respondents selected treatment in accordance with current guidelines, however in some scenarios, opinion was divided, and age did appear to be an independent factor that HCPs considered when making a treatment decision in this population.

Effects of 60 Hz magnetic field exposure on polymorphonuclear leukocyte activation.

We have investigated the effects of a sinusoidal 60 Hz magnetic field on free radical (superoxide anion) production, degranulation (beta-glucuronidase and lysozyme release) and viability in human neutrophils (PMNs). Experiments were performed blindly in very controlled conditions to examine the effects of a magnetic field in resting PMNs and in PMNs stimulated with a tumor promoter: phorbol 12-myristate 13-acetate (PMA). Exposure of unstimulated human PMNs to a 60 Hz magnetic field did not affect the functions examined. In contrast, exposure of PMNs to a 22 milliTesla (mT), 60 Hz magnetic field induced significant increases in superoxide anion (O2-) production (26.5%) and in beta-glucuronidase release (53%) when the cells were incubated with a suboptimal stimulating dose of PMA. Release of lysozyme and lactate dehydrogenase was unchanged by the magnetic field, whether the cells were stimulated or not. A 60 Hz magnetic field did not have any effect on O2- generation by a cell-free system xanthine/xanthine oxidase, suggesting that a magnetic field could upregulate common cellular events (signal transduction) leading to O2- generation and beta-glucuronidase release. In conclusion, exposure of PMNs to a 22 mT, 60 Hz magnetic field potentiates the effect of PMA on O2- generation and beta-glucuronidase release. This effect could be the result of an alteration in the intracellular signaling.