Dairy cow trade-off preference for 2 different lying qualities: Lying surface and lying space.

Lying down is an important behavior for cows, contributing to their health and welfare. With dairy cows being housed for increasingly longer periods, if not year-round, it is important to ensure that dairy cow lying comfort is not compromised when they are housed. The aim of this study was to assess cow preference for 2 different qualities of lying area that appear to be important to cows-surface type and an open lying space-to better understand how to optimize lying comfort for cows when housed. Twenty-four Holstein dairy cows were used during the study, which took place in Scotland from July to November 2018. The study consisted of 6 experimental periods, each lasting a total of 21 d. Cows were tested 4 at a time and individually housed in their own test pen. Each pen had 3 lying surfaces: sand, mattress, and straw (2.4 m × 2.4 m each) with a freestall in the middle of each, which could be removed. Cows were given access to one surface at a time (training period) with a freestall for 2 d, and then given a choice of all 3 surfaces for 2 d. When given the choice with freestalls in position, cows spent, on average, the largest amount of their lying time on straw (46.6 ± 7.8%) followed by mattress (44.3 ± 12.4%). Freestalls were then removed and the training and choice phase was repeated on the following day, with cows, on average, spending the most time lying on straw (64.4 ± 7.2%). Finally, a freestall was refitted onto each cow's most preferred surface and the cows were given a choice between lying on their most preferred surface with a freestall (P1 + freestall) or on their second or third preferred surface without a freestall (P2 + open and P3 + open, respectively) for 3 d. During this final trade-off stage, of the 19 cows for which data were available, 14 cows chose to give up the opportunity to lie down on their most preferred surface to have more space on P2 + open and P3 + open, 3 cows chose to lie down on P1 + freestall, and 2 cows made no clear choice. Overall, cows spent the largest amount of their total lying time on their second most preferred surface as an open lying space (65.7 ± 6.9%) compared with their preferred surface with a freestall (20.5 ± 5.9%) and their third preferred surface as an open lying space (13.8 ± 3.7%). The results indicate that when lying down, these dairy cows value an open lying space more than the lying surface.

Overall survival analysis of EXAM, a phase III trial of cabozantinib in patients with radiographically progressive medullary thyroid carcinoma.

BACKGROUND: Primary analysis of the double-blind, phase III Efficacy of XL184 (Cabozantinib) in Advanced Medullary Thyroid Cancer (EXAM) trial demonstrated significant improvement in progression-free survival with cabozantinib versus placebo in patients with progressive medullary thyroid cancer (MTC). Final analysis of overall survival (OS), a key secondary endpoint, was carried out after long-term follow-up. PATIENTS AND METHODS: EXAM compared cabozantinib with placebo in 330 patients with documented radiographic progression of metastatic MTC. Patients were randomized (2:1) to cabozantinib (140 mg/day) or placebo. Final OS and updated safety data are reported. RESULTS: Minimum follow-up was 42 months. Kaplan-Meier analysis showed a 5.5-month increase in median OS with cabozantinib versus placebo (26.6 versus 21.1 months) although the difference did not reach statistical significance [stratified hazard ratio (HR), 0.85; 95% confidence interval (CI), 0.64-1.12; P = 0.24]. In an exploratory assessment of OS, progression-free survival, and objective response rate, cabozantinib appeared to have a larger treatment effect in patients with RET M918T mutation-positive tumors compared with patients not harboring this mutation. For patients with RET M918T-positive disease, median OS was 44.3 months for cabozantinib versus 18.9 months for placebo [HR, 0.60; 95% CI, 0.38-0.94; P = 0.03 (not adjusted for multiple subgroup analyses)], with corresponding values of 20.2 versus 21.5 months (HR, 1.12; 95% CI, 0.70-1.82; P = 0.63) in the RET M918T-negative subgroup. Median treatment duration was 10.8 months with cabozantinib and 3.4 months with placebo. The safety profile for cabozantinib remained consistent with that of the primary analysis. CONCLUSION: The secondary end point was not met in this final OS analysis from the trial of cabozantinib in patients with metastatic, radiographically progressive MTC. A statistically nonsignificant increase in OS was observed for cabozantinib compared with placebo. Exploratory analyses suggest that patients with RET M918T-positive tumors may experience a greater treatment benefit with cabozantinib. TRIAL REGISTRATION NUMBER: NCT00704730.

Barriers to lung cancer care: health professionals' perspectives.

PURPOSE: Globally, lung cancer is the most common cancer and the leading cause of cancer death. Problematically, there is a wide variation in the management and survival for people with lung cancer and there is limited understanding of the reasons for these variations. To date, the views of health professionals across relevant disciplines who deliver such care are largely absent. The present study describes Australian health professionals' views about barriers to lung cancer care to help build a research and action agenda for improving lung cancer outcomes. METHODS: Qualitative semi-structured interviews were undertaken with a multidisciplinary group of 31 Australian health professionals working in lung cancer care for an average of 16 years (range 1-35 yrs.; SD = 10.2) seeing a mean of 116 patients annually. RESULTS: Three superordinate themes were identified: illness representations, cultural influences, and health system context. Illness representations included three themes: symptoms attributed as smoking-related but not cancer, health-related stigma, and therapeutic nihilism. Cultural influence themes included Indigenous health care preferences, language and communication, and sociodemographic factors. Health system context included lack of regional services and distance to treatment, poor care coordination, lack of effective screening methods, and health professional behaviours. CONCLUSIONS: Fractured and locally isolated approaches routinely confound responses to the social, cultural and health system complexities that surround a diagnosis of lung cancer and subsequent treatment. Improving outcomes for this disadvantaged patient group will require government, health agencies, and the community to take an aggressive, integrated approach balancing health policy, treatment priorities, and societal values.

A phase I trial of vertical inhibition of IGF signalling using cixutumumab, an anti-IGF-1R antibody, and selumetinib, an MEK 1/2 inhibitor, in advanced solid tumours.

BACKGROUND: We completed a phase I clinical trial to test the safety and toxicity of combined treatment with cixutumumab (anti-IGF-1R antibody) and selumetinib (MEK 1/2 inhibitor). METHODS: Patients with advanced solid tumours, refractory to standard therapy received selumetinib hydrogen sulphate capsules orally twice daily, and cixutumumab intravenously on days 1 and 15 of each 28-day cycle. The study used a 3+3 design, with a dose-finding cohort followed by an expansion cohort at the maximally tolerated dose that included pharmacokinetic and pharmacodynamic correlative studies. RESULTS: Thirty patients were enrolled, with 16 in the dose-finding cohort and 14 in the expansion cohort. Grade 3 or greater toxicities included nausea and vomiting, anaemia, CVA, hypertension, hyperglycaemia, and ophthalmic symptoms. The maximally tolerated combination dose was 50 mg twice daily of selumetinib and 12 mg kg(-1) every 2 weeks of cixutumumab. Two patients achieved a partial response (one unconfirmed), including a patient with BRAF wild-type thyroid carcinoma, and a patient with squamous cell carcinoma of the tongue, and six patients achieved time to progression of >6 months, including patients with thyroid carcinoma, colorectal carcinoma, and basal cell carcinoma. Comparison of pre- and on-treatment biopsies showed significant suppression of pERK and pS6 activity with treatment. CONCLUSIONS: Our study of anti-IGF-1R antibody cixutumumab and MEK 1/2 inhibitor selumetinib showed that the combination is safe and well-tolerated at these doses, with preliminary evidence of clinical benefit and pharmacodynamic evidence of target inhibition.

Phase I study of capecitabine combined with radioembolization using yttrium-90 resin microspheres (SIR-Spheres) in patients with advanced cancer.

BACKGROUND: This was a prospective single-centre, phase I study to document the maximum tolerated dose (MTD), dose-limiting toxicity (DLT), and the recommended phase II dose for future study of capecitabine in combination with radioembolization. METHODS: Patients with advanced unresectable liver-dominant cancer were enrolled in a 3+3 design with escalating doses of capecitabine (375-1000 mg/m(2) b.i.d.) for 14 days every 21 days. Radioembolization with (90)Y-resin microspheres was administered using a sequential lobar approach with two cycles of capecitabine. RESULTS: Twenty-four patients (17 colorectal) were enrolled. The MTD was not reached. Haematologic events were generally mild. Common grade 1/2 non-haematologic toxicities included transient transaminitis/alkaline phosphatase elevation (9 (37.5%) patients), nausea (9 (37.5%)), abdominal pain (7 (29.0%)), fatigue (7 (29.0%)), and hand-foot syndrome or rash/desquamation (7 (29.0%)). One patient experienced a partial gastric antral perforation with a capecitabine dose of 750 mg/m(2). The best response was partial response in four (16.7%) patients, stable disease in 17 (70.8%) and progression in three (12.5%). Median time to progression and overall survival of the metastatic colorectal cancer cohort was 6.4 and 8.1 months, respectively. CONCLUSIONS: This combined modality treatment was generally well tolerated with encouraging clinical activity. Capecitabine 1000 mg/m(2) b.i.d. is recommended for phase II study with sequential lobar radioembolization.

Magnetic properties of granular CoCrPt:SiO 2 thin films deposited on GaSb nanocones.

We report on the effect of microstructure and geometrically induced modifications of the magnetic properties of granular CoCrPt:SiO2 films with weakly interacting magnetic grains deposited on pre-structured GaSb nanocone templates fabricated by an ion erosion technique. By tuning the irradiation conditions, nanocone patterns of different cone sizes were prepared (from 28 to 120 nm in diameter and 32 to 330 nm high, respectively). The influence of the intergranular exchange coupling was also investigated by varying the SiO2 content from 8 to 12 at.%. Deposition of CoCrPt:SiO2 on samples with small nanocones leads to a close magnetic grain packing, which results in the formation of extended magnetic domains larger than the average distance between the GaSb cones. In contrast, on larger nanocones, the magnetic coating grows on the side-walls, with a large separation between neighboring cones, leading to magnetic single-domain regions, which are correlated to the underlying structure. Magnetometry indicates that both remanence and coercivity decrease with increasing cone size and/or SiO2 content due to a combined effect of the angular distribution of the magnetic easy axis of the grains and the intergranular exchange coupling strength.

Thromboprophylaxis for lung cancer patients--multimodality assessment of clinician practices, perceptions and decision support tools.

PURPOSE: The purpose of this study was to report the opinions and self-reported practices of clinicians, as well as the availability of decision support tools, regarding appropriate thromboprophylaxis for patients with lung cancer to identify variation in practice and/or divergence from evidence-based clinical practice guidelines (CPG). METHODS: A computer-generated survey (SurveyMonkey software) was distributed to surgical, radiation and medical oncologists with lung cancer specialisation, via membership of the Australian Lung Cancer Trials Group (ALTG) from May to September 2013. RESULTS: Seventy-two clinicians, from public, private, specialist and general hospitals, completed the survey (46% response rate). Hospital-endorsed CPG were widely available (91%); however, these routinely lacked robust recommendations for the ambulatory care setting (98%) and risk stratification tools (65%). Clinicians consistently identified ambulatory care treatment modalities (chemotherapy, alone or in combination with radiotherapy) as having similar (high) thrombotic risk as surgery. Timing and duration of pharmacological thromboprophylaxis prescribing among surgical oncologists varied and were divergent from guideline recommendations. Fifty-eight percent of surveyed clinicians cited a lack of high-quality data to guide preventative strategies in lung cancer patients. CONCLUSION: Clinicians consistently identified patients with lung cancer as having a high thromboembolic risk in both ambulatory and surgical settings, but with differences in recommendations and variation in practice. CPG lacked robust recommendations for the ambulatory care setting, the main arena for the multimodality lung cancer treatment paradigm.

Rapid identification of bacteria from bioMérieux BacT/ALERT blood culture bottles by MALDI-TOF MS.

Several studies have reported poor results when trying to identify microorganisms directly from the bioMérieux BacT/ALERT blood culture system using matrix-assisted laser desorption/ionisation-time of flight (MALDI-TOF) mass spectrometry. The aim of this study is to evaluate two new methods, Sepsityper and an enrichment method for direct identification of microorganisms from this system. For both methods the samples were processed using the Bruker Microflex LT mass spectrometer (Biotyper) using the Microflex Control software to obtain spectra. The results from direct analysis were compared with those obtained by subculture and subsequent identification. A total of 350 positive blood cultures were processed simultaneously by the two methods. Fifty-three cultures were polymocrobial or failed to grow any organism on subculture, and these results were not included as there was either no subculture result, or for polymicrobial cultures it was known that the Biotyper would not be able to distinguish the constituent organisms correctly. Overall, the results showed that, contrary to previous reports, it is possible to identify bacteria directly from bioMérieux blood culture bottles, as 219/297 (74%) correct identifications were obtained using the Bruker Sepsityper method and 228/297 (77%) were obtained for the enrichment method when there is only one organism was present. Although the enrichment method was simpler, the reagent costs for the Sepsityper method were approximately pound 4.00 per sample compared to pound 0.50. An even simpler and cheaper method, which was less labour-intensive and did not require further reagents, was investigated. Seventy-seven specimens from positive signalled blood cultures were analysed by inoculating prewarmed blood agar plates and analysing any growth after 1-, 2- and 4-h periods of incubation at 37 degrees C, by either direct transfer or alcohol extraction. This method gave the highest number of correct identifications, 66/77 (86%), and was cheaper and less labour-intensive than either of the two above methods.

Management of medullary thyroid cancer.

Molecular genetics analyses have indicated that approximately 55% of medullary thyroid cancer (MTC) tumors bear activating mutations of the RET gene, including inherited and sporadic cases. Tumoral RET mutations, especially M918T, have a strong negative prognostic impact. RET is the most important target for recent systemic therapy trials of MTC, along with vascular endothelial growth factor receptors. This review discusses promising recent clinical trials data for multikinase inhibitors including motesanib, vandetanib, sunitinib, sorafenib, and cabozantinib/XL184. Across multiple studies reported to date, RET mutations, although prevalent in these subjects, have not proven so far to predict whether patients will respond to multikinase inhibitors. In addition to comparing available data for efficacy and toxicity of these agents, the review focuses on critical questions related to appropriate selection of MTC patients for systemic treatment, and how best to integrate these therapies with established modalities of surgery and radiation therapy.

Snakebite admissions in Zimbabwe: pattern, clinical presentation and management.

OBJECTIVE: To describe the toxicoepidemiology of snakebite admissions to eight major referral hospitals in Zimbabwe. DESIGN: Retrospective and descriptive case review. SETTING: Four central hospitals (i.e., Harare, Parirenyatwa, Mpilo and United Bulawayo Hospitals) and four provincial hospitals (i,e., Gwanda, Bindura, Gweru and Mutare hospitals). MAIN OUTCOME MEASURES: Parameters assessed for included patient demographics e.g. age and gender, length of hospital stay, circumstances leading to snakebite, season and time of day of bite, culprit species, clinical presentation, management before and after admission, and outcome. RESULTS: There were a total of 273 admissions due to snakebite. Over 60% of bites were to the feet and about 36% were to the arms and hands. The type of snake involved was recorded in 14.6% (40) the cases with puff adders (Bitis arietans) being the most commonly implicated species. First aid and other pre-hospital treatments were recorded in 38 cases with tourniquets employed in 24 cases (63.2%) and 13 patients visiting a traditional medical practitioner before going to hospital. There were similar proportions of males to females admitted with snakebite and the case fatality rate in this study was 2.9%. CONCLUSION: Most bites from snakes in Zimbabwe occur to the feet and are probably from puff adders. The torniquet appears to be the most commonly employed first aid measure for snakebite in Zimbabwe, and snakebite victims still consult traditional healers.

Evolving Practice Pattern of Palliative Radiation Therapy for Bone Metastases from Lung Cancer in Australia.

AIMS: Radiation therapy is an effective treatment for bone metastases. Single-fraction conformal radiation therapy (SF-CRT) is equally effective as multifraction radiation therapy for the management of uncomplicated bone metastases. There has been a rapid development of advanced radiation therapy techniques (ART) in radiation oncology. We evaluated the changing pattern of SF-CRT and ART use for the management of bone metastases in lung cancer. MATERIALS AND METHODS: This was a state-wide population-based cohort of lung cancer patients from Victoria, Australia, who received radiation therapy for bone metastases between 2012 and 2017. The primary outcomes were proportion of radiation therapy courses using: SF-CRT and ART. We identified a subcohort in which radiation therapy was delivered at the end of life (EOL), i.e. within 30 days of death. The Cochran-Armitage test for trend was used to evaluate the change in pattern of SF-CRT and ART use over time. Multivariable analyses were used to identify factors associated with the primary outcomes. RESULTS: Of the 4335 courses of radiation therapy for bone metastases in lung cancer, 20% were SF-CRT - increasing from 19% in 2012 to 26% in 2017 (P-trend = 0.004). In multivariate analyses, treatment to the rib, shoulder, hip or extremities, and treatment in public institutions were independently associated with SF-CRT use, but the effect of year of radiation therapy was no longer significant. Five per cent of radiation therapy was delivered using ART, increasing markedly from 2016 onwards (P-trend < 0.001). In multivariate analyses, treatment in private institutions and more recent years of treatment were independently associated with the use of ART. There were 587 courses of radiation therapy delivered at the EOL, with SF-CRT more commonly used closer to death - 53%, 29% and 25% of radiation therapy within 7 days, 8-14 days and 15-30 days of death, respectively. CONCLUSION: SF-CRT continued to be underutilised for bone metastases in lung cancer in Australia, including at the EOL. We observed an increase in ART use for bone metastases from 2016, which occurred contemporaneously with changes in government funding.

Impact of COVID-19 on cancer service delivery: a follow-up international survey of oncology clinicians.

BACKGROUND: The COVID-19 pandemic has had a vast impact on cancer service delivery around the world. Previously reported results from our international survey of oncology clinicians, conducted through March-April 2020, found that clinicians reported altering management in both the curative and palliative settings and not in proportion to the COVID-19 case burden in their region of practice. This follow-up survey, conducted from 27th September to 7th November 2020, aimed to explore how attitudes and practices evolved over the 2020 pandemic period. PARTICIPANTS AND METHODS: Participants were medical, radiation and surgical oncologist and trainees. Surveys were distributed electronically via ESMO and other collaborating professional societies. Participants were asked to compare their practice prior to the pandemic to both the period of March-April 2020, referred to as the 'early' period, and the current survey period, referred to as the 'later' period. RESULTS: One hundred and seventy-two oncology clinicians completed the survey. The majority of respondents were medical oncologists (n = 136, 79%) and many were from Europe (n = 82, 48%). In the 'early' period, 88% (n = 133) of clinicians reported altering their practice compared to 63% (n = 96) in the 'later' period. Compared to prior to the pandemic, clinicians reported fewer new patient presentations in the 'early' period and a trend towards more patients presenting with advanced disease in the 'later' period. CONCLUSIONS: Results indicate a swing back towards pre-COVID-19 practices despite an increase in the rate of cumulative COVID-19 cases across 2020. The impact of these changes on cancer associated morbidity and mortality remains to be measured over the months and years to come.

Long-term Survival with 18-Fluorodeoxyglucose Positron Emission Tomography-directed Therapy in Non-small Cell Lung Cancer with Synchronous Solitary Brain Metastasis.

AIMS: At diagnosis, <1% of patients with non-small cell lung cancer (NSCLC) have synchronous solitary brain metastasis (SSBM). In prior cohorts without 18-fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT) staging, definitive treatment to intracranial and intrathoracic disease showed a 5-year overall survival (OS) of 11-21%. We investigated the long-term survival outcomes for patients with SSBM NSCLC, diagnosed in the FDG-PET/CT era and treated definitively with local therapies to both intracranial and intrathoracic sites of disease. MATERIALS AND METHODS: This retrospective study assessed patients staged with FDG-PET/CT who received definitive lung and SSBM treatment from February 1999 to December 2017. A lung-molecular graded prognostic assessment (lung-molGPA) score was assigned for each patient using age, performance status score, and, where carried out, molecular status. Overall survival and progression-free survival (PFS) were calculated using Kaplan-Meier methods. Cox proportional hazard models determined OS and PFS prognostic factors. RESULTS: Forty-nine patients newly diagnosed with NSCLC and SSBM had a median age of 63 years (range 34-76). The median follow-up of all patients was 3.9 years. Thirty-three patients (67%) had ≥T2 disease, 23 (47%) had ≥N2. At 2 years, 45% of first failures were intracranial only (95% confidence interval 30-59). At 3 and 5 years, OS was 45% (95% confidence interval 32-63) and 30% (95% confidence interval 18-51), respectively. In ≥N1 disease, 5-year OS was 34% (95% confidence interval 18-63). The 3- and 5-year PFS was 8% (95% confidence interval 3-22) and 0%, respectively. Higher lung-molGPA was associated with longer OS (hazard ratio 0.26, 95% confidence interval 0.11-0.61, P = 0.002). Higher lung-molGPA (hazard ratio 0.33, 95% confidence interval 0.15-0.71, P = 0.005) and lower N-stage (hazard ratio 1.56, 95% confidence interval 1.13-2.15, P = 0.007) were associated with longer PFS. CONCLUSIONS: Definitive treatment of patients with NSCLC and SSBM staged with FDG-PET/CT can result in 5-year survivors, including those with ≥N1 disease.

Medicine prices, availability, and affordability in 36 developing and middle-income countries: a secondary analysis.

BACKGROUND: WHO and Health Action International (HAI) have developed a standardised method for surveying medicine prices, availability, affordability, and price components in low-income and middle-income countries. Here, we present a secondary analysis of medicine availability in 45 national and subnational surveys done using the WHO/HAI methodology. METHODS: Data from 45 WHO/HAI surveys in 36 countries were adjusted for inflation or deflation and purchasing power parity. International reference prices from open international procurements for generic products were used as comparators. Results are presented for 15 medicines included in at least 80% of surveys and four individual medicines. FINDINGS: Average public sector availability of generic medicines ranged from 29.4% to 54.4% across WHO regions. Median government procurement prices for 15 generic medicines were 1.11 times corresponding international reference prices, although purchasing efficiency ranged from 0.09 to 5.37 times international reference prices. Low procurement prices did not always translate into low patient prices. Private sector patients paid 9-25 times international reference prices for lowest-priced generic products and over 20 times international reference prices for originator products across WHO regions. Treatments for acute and chronic illness were largely unaffordable in many countries. In the private sector, wholesale mark-ups ranged from 2% to 380%, whereas retail mark-ups ranged from 10% to 552%. In countries where value added tax was applied to medicines, the amount charged varied from 4% to 15%. INTERPRETATION: Overall, public and private sector prices for originator and generic medicines were substantially higher than would be expected if purchasing and distribution were efficient and mark-ups were reasonable. Policy options such as promoting generic medicines and alternative financing mechanisms are needed to increase availability, reduce prices, and improve affordability.

Nanocap arrays of granular CoCrPt:SiO2 films on silica particles: tailoring of the magnetic properties by Co+ irradiation.

An approach for tailoring the magnetic properties by ion irradiation of granular perpendicular CoCrPt:SiO(2) films grown on silica particles with sizes down to 10 nm was investigated. The as-prepared samples reveal an intriguing scaling dependence of the coercive field and remnant magnetization: both parameters are found to decrease with decreasing particle size. However, Co(+) irradiation at a low fluence of 0.5 x 10(14) cm(-2) already results in an opposite scaling behavior. It is assumed that this modification is due to the enhancement of the intergranular magnetic exchange coupling of the granular CoCrPt:SiO(2) film initiated by Co(+) irradiation resulting in a modified reversal behavior. Further increase of the irradiation fluence beyond 1.6 x 10(14) ions cm(-2) leads to a degradation of the magnetic layer properties, lowering the remnant magnetization and the coercive field in the easy-axis direction. Moreover, the local magnetic properties of the samples were analyzed by magnetic force microscopy revealing magnetic multi-domain cap structures.