Advanced cancer patients' attitudes towards, and experiences with, screening for somatic mutations in tumours: a qualitative study.

Somatic mutations in key oncogenes in non-small cell lung cancer (NSCLC) and melanoma are important determinants of tumour sensitivity to targeted therapies. Molecular screening for these predictive biomarkers is routinely used to inform treatment decisions; however, little is known about how best to communicate testing and results to patients. This qualitative study aimed to explore advanced cancer patients' attitudes and experiences regarding somatic tumour screening to identify their information and support needs. Sixteen NSCLC and eight melanoma patients who had undergone screening participated in a semi-structured face-to-face or telephone interview exploring their understanding, views, preferences and needs regarding screening. Interviews were audiotaped, transcribed and analysed for thematic patterns. Participants expressed positive views and unequivocal acceptance of screening, and understood its role in guiding treatment selection. They preferred to receive information verbally through simple, non-technical language from their oncologist with additional take-home materials. Patients were interested in learning about their test results, but wanted discussion to be focused on practical matters relevant to treatment. While receiving their screening results was not considered burdensome, information overload and cancer-related distress were identified as barriers to test comprehension. Patients may benefit from information and decision-related tools to better understand genomic information and adequately support psychosocial outcomes.

A phase III randomized trial of adding topical nitroglycerin to first-line chemotherapy for advanced nonsmall-cell lung cancer: the Australasian lung cancer trials group NITRO trial.

BACKGROUND: We sought to determine whether the substantial benefits of topical nitroglycerin with first-line, platinum-based, doublet chemotherapy in advanced nonsmall-cell lung cancer (NSCLC) seen in a phase II trial could be corroborated in a rigorous, multicenter, phase III trial. PATIENTS AND METHODS: Patients starting one of five, prespecified, platinum-based doublets as first-line chemotherapy for advanced NSCLC were randomly allocated treatment with or without nitroglycerin 25 mg patches for 2 days before, the day of, and 2 days after, each chemotherapy infusion. Progression-free survival (PFS) was the primary end point. RESULTS: Accrual was stopped after the first interim analysis of 270 events. Chemotherapy was predominantly with carboplatin and gemcitabine (79%) or carboplatin and paclitaxel (18%). The final analysis included 345 events in 372 participants with a median follow-up of 33 months. Topical nitroglycerin had no demonstrable effect on PFS [median 5.0 versus 4.8 months, hazard ratio (HR) = 1.07, 95% confidence interval (CI) 0.86-1.32, P = 0.55], overall survival (median 11.0 versus 10.3 months, HR = 0.99, 95% CI 0.79-1.24, P = 0.94), or objective tumor response (31% versus 30%, relative risk = 1.03, 95% CI 0.82-1.29, P = 0.81). Headache, hypotension, syncope, diarrhea, dizziness, and anorexia were more frequent in those allocated nitroglycerin. CONCLUSION: The addition of topical nitroglycerin to carboplatin-based, doublet chemotherapy in NSCLC had no demonstrable benefit and should not be used or pursued further. CLINICAL TRIALS NUMBER: Australian New Zealand Clinical Trials Registry Number ACTRN12608000588392.

Accelerated BEP for metastatic germ cell tumours: a multicenter phase II trial by the Australian and New Zealand Urogenital and Prostate Cancer Trials Group (ANZUP).

BACKGROUND: This Australian single-arm, multicenter, phase II trial evaluated feasibility, tolerability and activity of accelerated bleomycin, etoposide and cisplatin (BEP) as first-line chemotherapy for metastatic germ cell tumours. PATIENTS AND METHODS: Patients were planned to receive cisplatin 20 mg/m(2) and etoposide 100 mg/m(2) days 1-5, and pegfilgrastim 6 mg day 6, all repeated every 2 weeks for four cycles (three cycles for good prognosis). Bleomycin was given at 30 000 IU weekly to a total of 12 doses (9 doses for good prognosis). Primary end point was feasibility, defined as the proportion of patients able to complete the etoposide and cisplatin components of BEP and be eligible to receive a fourth cycle of BEP by day 50. RESULTS: Twelve poor, 16 intermediate and 15 good prognosis (n = 43) eligible patients were enrolled. Two patients aged >40 years were ineligible and excluded from analyses. The regimen was feasible in 86%, not feasible in 7% and not assessable in 7% of patients. Most common grade 3/4 adverse events were non-neutropenic infection (16%) and febrile neutropenia (12%). Complete response (CR) to chemotherapy and surgery was achieved in 33% poor-prognosis, 81% intermediate-prognosis and 100% good-prognosis patients. At median follow-up of 27 months (range 6-42), the 2-year progression-free survival was 50% for poor-prognosis, 94% for intermediate-prognosis and 92% for good-prognosis patients. CONCLUSION: Accelerated BEP is feasible and tolerable. Efficacy data appear to be promising. This trial and a similar UK study provide the rationale for a randomised trial comparing accelerated versus standard BEP. Australian New Zealand Clinical Trials Registry Registration number. ACTRN 12607000294459.

Ecodesign of Kesterite Nanoparticles for Thin Film Photovoltaics at Laboratory Scale.

This manuscript investigates the efficient synthesis of copper zinc tin sulfide (CZTS) nanoparticles for CZTS thin film solar cell applications with a primary focus on environmental sustainability. Underpinning the investigation is an initial life-cycle assessment (LCA) analysis. This LCA analysis is conducted to evaluate the environmental impact of different synthesis volumes, providing crucial insights into the sustainability of the synthesis process by considering the flows of material and energy associated with the process. Life-cycle assessment results demonstrate that significant reductions to the environmental impact can be made by increasing the synthesis volume of CZTS nanoparticle ink. Using a 5-fold increase in volume can reduce all 11 investigated environmental impacts by up to 35.6%, six of these impacts demonstrating reductions >10% and the amount of global warming potential is reduced by 21.4%. Motivated by the LCA results, COMSOL simulations are employed to understand the fluid flow patterns in large-scale fabrication. Various sizes and speeds of stirrer bars are investigated in these simulations, and it is determined that a 50 mm stir bar at 200 rpm represents the optimal configuration for the synthesis process in a 500 mL flask. Subsequently, large-batch CZTS nanoparticle inks are synthesized using these parameters and compared to small-batch samples. The light absorbers are characterized using Raman spectroscopy and X-ray diffraction, confirming favorable properties with close-to-ideal elemental ratios in large-batch synthesis. Finally, solar cell devices fabricated utilizing CZTSSe absorbers from the large volume synthesis process demonstrate comparable performance to those fabricated using small-batch synthesis, with uniform power conversion efficiencies of around 5% across the substrate. This study highlights the potential of large-volume CZTS nanoparticle synthesis for efficient and environmentally friendly CZTS solar cell fabrication, contributing to the advancement of sustainable renewable energy technologies.

Outcome and racing performance following standing fracture repair in 245 horses.

BACKGROUND: Repair of sagittal proximal phalanx (P1) and parasagittal metacarpal/metatarsal III (MC/MTIII) fractures has evolved over recent decades from a procedure carried out solely under general anaesthesia, to one commonly performed under standing sedation. To date, standing fracture repair has not been evaluated for large cohorts. OBJECTIVES: To determine short-term (survival to discharge) and long-term (return to racing) outcomes of horses undergoing standing repair of MC/MTIII and P1 fractures, and to compare pre-surgical and post-surgical racing performance. STUDY DESIGN: Single-centre retrospective cohort study. METHODS: Retrospective clinical record review of 245 cases undergoing standing repair of MC/MTIII or P1 fractures, 1 January 2007-30 June 2021. Data on signalment, fracture configuration and complications were collected and full race records were retrieved from the Racing Post Database (wwww.racingpost.com). Chi-squared and Mann-Whitney U tests were used to determine any difference in variables between horses that raced after surgery compared to those that did not. McNemar change and Wilcoxon signed-rank tests were used to compare pre- and post-surgical racing performance, p ≤ 0.05. RESULTS: Ninety-eight percent [95% confidence interval (CI): 96.2%-99.7%] of horses survived hospital discharge, and 75.1% (95% CI: 68.9%-81.4%) raced after surgery, a median of 241 days later. Horses that raced post-surgery were significantly less likely to have suffered from complications during hospitalisation than those that did not race again [17.3% (95% CI: 11%-24%) vs. 36.5% (95% CI: 23%-50%), p = 0.005]. Comparing pre- and post-operative racing performance, there was no significant difference in earnings per start [median £628.00, interquartile range (IQR) 115.90-1934.80 vs. £653.20, 51.00-1886.40, p = 0.7] or proportion of horses winning [51% (95% CI: 41%-61%) vs. 54% (95% CI: 44%-64%), p = 0.8] or being placed first-third [77% (95% CI: 68%-85%) vs. 71% (95% CI: 62%-80%, p = 0.5] in at least one race. MAIN LIMITATIONS: Retrospective nature of study with reliance on clinical records and public databases, limiting data available for analysis. CONCLUSIONS: Standing fracture repair is a viable treatment option for MC/MTIII or P1 fractures that returns horses to the racetrack within an acceptable time frame and is capable of restoring pre-surgical athletic ability.

Smoking is associated with impaired verbal learning and memory performance in women more than men.

Vascular contributions to cognitive impairment and dementia (VCID) include structural and functional blood vessel injuries linked to poor neurocognitive outcomes. Smoking might indirectly increase the likelihood of cognitive impairment by exacerbating vascular disease risks. Sex disparities in VCID have been reported, however, few studies have assessed the sex-specific relationships between smoking and memory performance and with contradictory results. We investigated the associations between sex, smoking, and cardiovascular disease with verbal learning and memory function. Using MindCrowd, an observational web-based cohort of ~ 70,000 people aged 18-85, we investigated whether sex modifies the relationship between smoking and cardiovascular disease with verbal memory performance. We found significant interactions in that smoking is associated with verbal learning performance more in women and cardiovascular disease more in men across a wide age range. These results suggest that smoking and cardiovascular disease may impact verbal learning and memory throughout adulthood differently for men and women.

Two separate, large cohorts reveal potential modifiers of age-associated variation in visual reaction time performance.

To identify potential factors influencing age-related cognitive decline and disease, we created MindCrowd. MindCrowd is a cross-sectional web-based assessment of simple visual (sv) reaction time (RT) and paired-associate learning (PAL). svRT and PAL results were combined with 22 survey questions. Analysis of svRT revealed education and stroke as potential modifiers of changes in processing speed and memory from younger to older ages (ntotal = 75,666, nwomen = 47,700, nmen = 27,966; ages 18-85 years old, mean (M)Age = 46.54, standard deviation (SD)Age = 18.40). To complement this work, we evaluated complex visual recognition reaction time (cvrRT) in the UK Biobank (ntotal = 158,249 nwomen = 89,333 nmen = 68,916; ages 40-70 years old, MAge = 55.81, SDAge = 7.72). Similarities between the UK Biobank and MindCrowd were assessed using a subset of MindCrowd (UKBb MindCrowd) selected to mirror the UK Biobank demographics (ntotal = 39,795, nwomen = 29,640, nmen = 10,155; ages 40-70 years old, MAge = 56.59, SDAge = 8.16). An identical linear model (LM) was used to assess both cohorts. Analyses revealed similarities between MindCrowd and the UK Biobank across most results. Divergent findings from the UK Biobank included (1) a first-degree family history of Alzheimer's disease (FHAD) was associated with longer cvrRT. (2) Men with the least education were associated with longer cvrRTs comparable to women across all educational attainment levels. Divergent findings from UKBb MindCrowd included more education being associated with shorter svRTs and a history of smoking with longer svRTs from younger to older ages.

A lateral approach for screw repair in lag fashion of spiral third metacarpal and metatarsal medial condylar fractures in horses.

OBJECTIVE: To describe a lateral approach for screw fixation in lag fashion of simple spiral medial condylar fractures of the third metacarpus/metatarsus (MC3/MT3). STUDY DESIGN: Case series. ANIMALS: Thoroughbred racehorses (n=9). METHODS: Nondisplaced medial MC3/MT3 condylar fractures (3 thoracic, 6 pelvic limbs), with mean length 126 mm (range, 91-151 mm) were repaired by internal fixation, under general anesthesia, using multiple 4.5 mm cortical screws inserted in lag fashion from the lateral aspect of the limb, using radiographic or fluoroscopic guidance. Horses were recovered from anesthesia in half-limb casts; 7 unassisted and 2 using a rope-recovery system. Horses had 2 months box rest, 1 month in-hand walking, and follow-up radiographic examination at 3 months. RESULTS: Horses recovered uneventfully from anesthesia. Five horses raced; 1 returned to training, was persistently lame, and was retired to stud; 2 were retired directly to stud; and 1 horse was lost to follow-up. CONCLUSIONS: MC3/MT3 medial condylar fractures were successfully repaired by screws inserted n lag fashion form the lateral aspect. CLINICAL RELEVANCE: Use of a lateral approach to medial condylar MC3/MT3 fractures allows screw insertion perpendicular to the fracture plane without interference with palmar/plantar soft tissue structures or from the splint bones. Although repair was performed under general anesthesia, the technique should be adaptable to application in standing horses.

Radiographic Identification of Osseous Cyst- Like Lesions in the Distal Phalanx in 22 Lame Thoroughbred Horses Managed Conservatively and Their Racing Performance.

Reasons for performing study: To investigate the racing performance of Thoroughbred horses with osseous cyst-like lesions (OCLLs) in the distal phalanx causing lameness and treated conservatively. Objectives: To assess horses' ability to race and perform after radiographic identification of OCLL in the distal phalanx of Thoroughbred horses with lameness at the time of detection and undergoing conservative treatment. Study Design: Retrospective case control study. Methods: The clinical database of one equine clinic was reviewed in a 10-year period for Thoroughbreds showing lameness localized to the foot and a radiographic diagnosis of OCLL in the distal phalanx. Sex, age at time of detection of the OCLL, degree of lameness, affected limb, and treatment were recorded. Successful performance of horses was assessed by racing at least once after detection of the OCLL and maximum racing performance rating (RPR). Radiographic features such as size, location, sclerotic rim of the OCLL and irregularity of the articular surface of the distal phalanx were compared to successful performance using univariable statistical analysis. Successful performance of horses with OCLL was compared to a control group of maternal siblings by parametric testing. Results: Twenty-two horses met the inclusion criteria. Thirteen horses raced after the detection of OCLLs. Eight did not race, one case had not yet reached racing age, resulting in 62% (13/21) of racing age racing at least once. The number of successfully performing horses with an OCCL was significantly lower compared to their maternal siblings [p = 0.03, Odds ratio (OR) = 0.30]. If horses with OCLL in the distal phalanx raced, their RPR was similar to their maternal siblings. No significant association was found between radiographic features of OCLLs and successful performance, but OCLLs in the left forelimb carried a more favorable outcome for racing (p = 0.02, OR = 2.33 95%CI 1.27, 4.27) compared to OCLLs in any other limb. Conclusions: Horses with lameness and an OCLL in the distal phalanx managed conservatively are less likely to race when compared to their maternal siblings. If horses with OCLLs in the distal phalanx are able to race, their performance, measured as RPR, was comparable to their maternal siblings. Due to the small numbers in this study the results should be interpreted carefully.

Regional radiotherapy may improve outcomes in patients with early stage breast cancer undergoing breast conservation therapy.

BACKGROUND: Breast conservation therapy (BCT) is recommended as standard management of early breast cancer. The aim of this study was to retrospectively evaluate the results of BCT to identify prognostic factors predictive of treatment outcomes. PATIENTS AND METHODS: Four hundred and ninety-eight eligible women with unilateral stage I-II breast cancer who had undergone BCT were analyzed. RESULTS: The cumulative incidence of local recurrence (LR) was 1.9% and 3.7% at 3- and 5-years respectively. The 5-year disease-free, cancer-specific, and overall survival (DFS, CSS, OS) were 80.0%, 87.3% and 85.4% respectively. Significant independent predictors for LR included young age and absence of chemotherapy. Regional nodal radiotherapy was significantly associated with improved DFS and OS. CONCLUSION: Our results confirmed the efficacy of BCT in the treatment of early breast cancer and indicated that inclusion of regional nodal areas within the radiotherapy field might be beneficial in the BCT setting, particularly for patients with adverse risk features.

Prediction of reduction in aggressive behaviour of growing pigs using skin lesion traits as selection criteria.

Aggression at regrouping is a common issue in pig farming. Skin lesions are genetically and phenotypically correlated with aggression and have been shown to have a significant heritable component. This study predicts the magnitude of reduction in complex aggressive behavioural traits when using lesion numbers on different body regions at two different time points as selection criteria, to identify the optimum skin lesion trait for selection purposes. In total, 1146 pigs were mixed into new social groups, and skin lesions were counted 24 h (SL24h) and 3 weeks (SL3wk) post-mixing, on the anterior, centre and posterior regions of the body. An animal model was used to estimate genetic parameters for skin lesion traits and 14 aggressive behavioural traits. Estimated breeding values (EBVs) and phenotypic values were scaled and standardised to allow direct comparison across multiple traits. Individuals with SL24h and SL3wk EBVs in the least aggressive 10% of the population were compared with the population mean to predict the expected genetic and phenotypic response in aggressive behaviour to selection. At mixing, selection for low anterior lesions was predicted to affect substantially more behavioural traits of aggressiveness than lesions obtained on other body parts, with EBVs between -0.21 and -1.17 SD below the population mean. Individuals with low central SL24h EBVs also had low EBVs for aggressive traits (-0.33 to -0.55). Individuals with high SL3wk EBVs had low EBVs for aggression at mixing (between -0.24 and -0.53 SD below the population mean), although this was predicted to affect fewer traits than selection against SL24h. These results suggest that selection against anterior SL24h would result in the greatest genetic and phenotypic reduction in aggressive behaviour recorded at mixing. Selection for increased SL3wk was predicted to reduce aggression at mixing; however, current understanding about aggressive behaviour under stable social conditions is insufficient to recommend using this trait for selection purposes.

Mature results of a randomized trial of two doses of cisplatin for the treatment of ovarian cancer. Scottish Gynecology Cancer Trials Group.

PURPOSE: In 1992, we reported the first results of a randomized study in ovarian cancer, comprising two doses of cisplatin and indicated a significant difference (P = .0008) in median survival. Four years later, we now describe the results of this trial. PATIENTS AND METHODS: After a median follow-up of 4 years and 9 months, 115 of 159 cases of advanced ovarian cancer, originally randomized to receive six cycles of cyclophosphamide 750 mg/m2 and either a high dose (HD) of 100 mg/m2 cisplatin or a low dose (LD) of 50 mg/m2 (LD) cisplatin, have now died. RESULTS: The overall survival for HD and LD patients is 32.4% and 26.6%, respectively, and the overall relative death rate is 0.68 (P = .043). This represents a reduction in overall benefit with longer follow-up compared with the first 2 years (relative death rate of 0.52). Toxicity, particularly neurotoxicity, is still evident in the fourth year (10/31 on HD compared with 1/24 on LD). CONCLUSION: Our recommended dose of cisplatin in combination schedule is therefore 75 mg/m2, representing the optimal balance between efficacy and toxicity.

Social genetic effects influence reproductive performance of group-housed sows.

Group housing of gestating sows has implications for reproductive performance due to detrimental interactions between sows within groups. Reproductive records ( = 10,748) were obtained for 8,444 pedigreed nucleus sows housed in a single facility, formed into 1,827 static groups during gestation. Only data from complete groups were used to estimate genetic parameters for total born (TB), number born alive (NBA), and gestation length (GL) and to compare models extended to account for group effects. Censored data for sows which did not farrow (0.8% of records) were augmented with biologically meaningful values. Group sizes ranged from 2 to 10, in pens designed to hold 4, 8, or 10 sows per pen. Sows were grouped by parity, line, and mating date after d 35 of pregnancy. Heritability estimates were generally constant across all model alternatives at 0.11 ± 0.02 for TB and NBA and 0.32 ± 0.03 for GL. However, models for all traits were significantly ( < 0.05) improved through inclusion of terms for nongenetic group and social genetic effects (SGE). Group effects were no longer significant in models containing both terms. The proportional contributions of SGE () to phenotypic variances were very low (≤0.002 across traits), but their contributions to calculated total genetic variance (T) were significant. The differences between h and T ranged between 3 and 5% under simple models, increasing to 8 to 14% in models accounting for both covariances between additive direct (A) and SGE and the effects of varying group size on the magnitude of estimates for SGE. Estimates of covariance between A and SGE were sensitive to the modeling of dilution factors for group size. The models of best fit for litter size traits used a customized dilution based on sows/pen relative to the maximum sows/pen. The best model supported a reduction in SGE with increased space per sow, independent of maximum group size, and no significant correlation between A and SGE. The latter is expected if A and SGE reflect different trait complexes. It is suggested that the SGE estimated for reproductive traits represented the expression of an unobserved phenotype, such as sow aggression, of an individual on its pen mates. Further investigation into the use of competitive effects models for genetic evaluation of reproductive traits for group-housed sows could be considered a strategy to improve welfare and performance of group-housed sows.

Respiratory muscle training may improve respiratory function and obstructive sleep apnoea in people with cervical spinal cord injury.

STUDY DESIGN: This is a double-blind crossover case study series. OBJECTIVES: The objective of this study was to assess the feasibility of respiratory muscle training (RMT) as an effective intervention to improve lung function and obstructive sleep apnoea (OSA) in cervical spinal cord injury (SCI) patients. SETTING: This study was conducted in Australia. METHODS: Three adults (C5-6, AIS A-C) participated in this study. They trained with an RMT device (active or sham) for 4 weeks followed by 2 weeks of rest, and then trained with the alternate device for 4 weeks. RMT occurred twice daily, 5 days a week, and it consisted of three sets of 12 inspirations and three sets of 12 expirations. Training intensity commenced at 30% maximal inspiratory pressure (MIP) and 30% maximal expiratory pressure (MEP), which was increased every second day by 10%. Spirometry, MIP, MEP, polysomnography and Epworth Sleepiness Scale (ESS) were measured before and after every 4 weeks of training. RESULTS: After active RMT, vital capacity and inspiratory capacity improved from baseline in all participants (by 44%, 60% and 18% and by 18%, 46% and 5%, respectively); MIP improved by 40 and 17% from baseline in two subjects; and MEP improved in all participants. Two participants had OSA, and after active training their obstructive apnoea-hypopnoea index improved from 30 to 21events per hour and from 72 to 18 events per hour, and ESS marginally improved. Sham RMT resulted in minimal changes in all measures. CONCLUSION: RMT is feasible and likely effective to increase respiratory muscle strength, to improve lung function, and to reduce the severity of OSA and sleepiness in people with cervical SCI. A randomised controlled trial is planned to validate these findings and to examine respiratory-related morbidity and quality of life.

Genetic associations of short- and long-term aggressiveness identified by skin lesion with growth, feed efficiency, and carcass characteristics in growing pigs.

The objective of this study was to investigate the genetic relationships between skin lesion traits in group housed growing pigs as a measure of short- (in a newly mixed group) and long- (in a socially stable group) term aggression and commonly used commercial performance measures: growth, feed intake, feed efficiency, and carcass traits. Data on 2,413 growing pigs (138 groups) were available. Pigs were mixed into new social groups of 18 animals, and skin lesions were counted 24 h (SL24h) and 5 wk (SL5wk) postmixing. The animal model was used to estimate genetic parameters for skin lesion traits, test daily gain, lifetime daily gain, daily feed intake, feed efficiency (calculated as test daily gain divided by daily feed intake), loin depth, back fat, and HCW. Skin lesions had a heritable component, ranging from 0.08 for anterior SL24h to 0.22 for central SL5wk and would, therefore, be suitable as a method of phenotyping aggression for selection purposes. Significant positive genetic correlations were found between SL24h and SL5wk (0.46 to 0.81). Positive genetic correlations were also found between SL24h (central and posterior body regions) or SL5wk (all body regions) and the production traits lifetime daily gain, test daily gain, and HCW (0.29 to 0.54). Central SL24h, anterior SL5wk, and posterior SL5wk were found to correlate positively with feed efficiency (0.39 to 0.50), suggesting that pigs with more lesions convert feed more efficiently. Where significant, the magnitude of phenotypic correlations was low but positive (0.07 to 0.10). These results suggest that, genetically, animals that receive many lesions show improved performance compared to those with few lesions, except for anterior SL24h, which had previously been shown to be genetically positively correlated with the initiation of nonreciprocal attacks. It may, therefore, be possible, via selection against anterior skin lesions at mixing, to reduce this form of 1-sided aggression without adversely affecting production traits.

B-cell stimulation and prolonged immune deficiency are risk factors for non-Hodgkin's lymphoma in people with AIDS.

OBJECTIVES: To identify risk factors for non-Hodgkin's lymphoma (NHL) in people with HIV infection. DESIGN AND SETTING: Case-control study in Sydney, Australia. PARTICIPANTS AND METHODS: Two hundred and nineteen patients with AIDS-related NHL were compared with 219 HIV-infected controls without NHL, matched for CD4 positive cell count and date of specimen collection. Data on demographic, infectious, treatment-related and immunological factors were abstracted by medical record review. The association between demographic factors, sexually transmissible diseases, HIV-related opportunistic infections, anti-viral therapy, duration of immune deficiency and indices of immune stimulation and risk of NHL were derived for these groups. RESULTS: In a multivariate model, there were two independent groups of predictors of NHL risk. The first was duration of immunodeficiency, as measured by longer time since seroconversion (P for trend 0.008), and lower CD4 positive cell count 1 year prior to the time of NHL diagnosis (P for trend 0.009). The second predictor was B-cell stimulation, as indicated by higher serum globulin (a surrogate marker for serum immunoglobulin, P for trend 0.044) and HIV p24 antigenaemia [odds ratio (OR) for p24 positivity, 1.82; 95% confidence interval (CI), 1.15-2.88]. Indices of B-cell stimulation preceded the diagnosis of NHL by several years. Factors not related to NHL risk included clinical indices of Epstein-Barr virus infection and receipt of individual nucleoside analogue antiretroviral agents. Combination therapy with these agents was associated with a non-significant reduction in NHL risk (OR, 0.68; 95% CI, 0.39-1.18). CONCLUSIONS: Markers of long-standing immune deficiency and B-cell stimulation were associated with an increased risk of developing NHL. Unless the strongest risk factor for NHL, immune deficiency, can be reversed, NHL is likely to become proportionately more important as a cause of morbidity and mortality in people with HIV infection.

A longitudinal study of weight and fatness in sows from selection to parity five, using random regression.

This study examined the changes in BW, fatness, and genetic parameters for these traits over a sow's productive life, using random regression. Data for BW (kg) and fat depth at the P2 site (mm) were recorded repeatedly on 3,324 sows from selection to culling. There were up to 19 recording events, defined as: 20, 21, 26, and 29 wk of age, followed by records at mating, d 110 of gestation (d110), and weaning, for parities 1 through 5. In this population, sows continued growing through parity 5 but achieved 90% of this BW by 22 mo, which is the average age at remating after parity 3. In contrast, sows increased fat levels until just before parity 1 farrowing, when a plateau in permanent reserves was essentially established. Heritability estimates were 0.31 ± 0.08 and 0.36 ± 0.08 for BW and fatness, on average, from the random regression analyses. However, the greatest heritabilities were estimated from data recorded before the first farrowing and diminished with increasing age as residual variation increased. Trajectories of heritability estimates for both BW and fat from random regression show that genetic variation is available for selection to alter sow development patterns. However, due to relatively low genetic correlations between early and later BW, repeated BW measurements would be required to effectively alter mature sow BW, in particular. The solutions for development patterns were obtained for individual sows from the random regression model and were used to extrapolate the expected individual sow BW at 30 mo. Genetic solutions, including the intercept and slope for BW and fatness, were used to rank sows into quartiles. Results suggested that genetically heavier/fatter sows are more likely to successfully enter and stay in the breeding herd, thus demonstrating increased lifetime performance. However, there is also evidence to suggest that sows with high growth potential expressed later in life were disadvantaged with respect to their longevity and productivity. Therefore, a breeding goal combining efficient lean growth in finishers with limits to mature sow size could be beneficial to sow herd performance.

Body development in sows, feed intake and maternal capacity. Part 1: performance, pre-breeding and lactation feed intake traits of primiparous sows.

This study examined the genetic and phenotypic associations between finisher performance, pre-breeding body condition of the gilt, subsequent lactation feed intake and survival of the primiparous sow to farrow in the second parity. Complete data were available on ~2200 sows, along with additional cohort and historical performance data. Genetic variation was observed for average lactation feed intake (heritability: 0.18 ± 0.04), with a significant proportion of observed variation in average intake attributable to variation in lactation length. Weight and body condition (fatness) at finishing were very highly correlated genetically (0.89 ± 0.03 and 0.90 ± 0.02) and moderately correlated phenotypically (0.58 ± 0.01 and 0.58 ± 0.01) with weight and body condition before mating. Estimates of genetic (r(g)) and phenotypic (r(p)) correlations between feed intake recorded at finishing and average lactation feed intake (LADI) were moderate (r(g) = 0.26 ± 0.16 and 0.42 ± 0.22) and low (r(p) = 0.07 ± 0.02 and 0.08 ± 0.03), with r(g) dependent on the models and data subsets used for lactation intake. Non-unity genetic correlations imply that different genetic control mechanisms regulate feed intake during growth and lactation. Moderate genetic correlations between lactation feed intake with live weight (TWT) or growth rate (TADG) recorded at selection and live weight before mating (0.42 ± 0.11, 0.42 ± 0.11 and 0.37 ± 0.15) were considerably higher than the corresponding phenotypic correlations for LADI with TADG or 29WT (0.09 ± 0.02 and 0.08 ± 0.02). Correlations between fatness at selection (TFAT) or mating (29FT) and LADI were negative but not significantly different from 0. Overall, these data suggest that there is exploitable genetic variation for feed intake during lactation, and that selection is possible if lactation feed intakes are recorded. However, genetic correlations suggest that early growth seems to be related to lactation feed intake capacity. There was generally no strong evidence that selection for lean growth potential in dam lines will substantially diminish sow lactation intake capacity as a correlated response.

Body development in sows, feed intake and maternal capacity. Part 2: gilt body condition before and after lactation, reproductive performance and correlations with lactation feed intake.

Data on sow body weight (BW) and fatness (n = ~2250 pregnant sows) and reproductive data (including historical: n = ~18 000) were used to examine the genetic and phenotypic associations between body condition before and after farrowing, gestational outcomes, lactation feed intake and the gilts' ability to survive unculled to farrow in the second parity. Within-trait genetic correlations were very high between weight (0.77 ± 0.06) and fat depth (0.91 ± 0.04) recorded before farrowing and at weaning. Litter size traits were generally uncorrelated genetically with aspects of sow BW and body condition. However, genetic correlations indicated that sows producing heavier piglets at birth had litters with increased gain (0.36 ± 0.16), and were characterised by greater weight (-0.72 ± 0.08) and fat change (-0.19 ± 0.15) during lactation, reflected to a lesser extent by lower weight (-0.12 ± 0.11) and fatness (-0.17 ± 0.10) at weaning. Genetic correlations (r(a)) between reproductive traits and lactation feed intake were generally low, but favourable. However, lactation intake was positively correlated with measures of sow size (r(a) = ~0.55), such that selection for lactation feed intake would likely be accompanied by increased mature sow size. Phenotypic correlations (r(p)) showed that sow survival to the second parity (FAR12) was positively influenced by litter size and fat depth at weaning, supporting attributes of increased fatness before farrowing, less weight loss during lactation and an increased lactation intake.