The genomic and transcriptomic landscape of advanced renal cell cancer for individualized treatment strategies.

Differences in the clinical course and treatment responses in individual patients with advanced renal cell carcinoma (RCC) can largely be explained by the different genomics of this disease. To improve the personalized treatment strategy and survival outcomes for patients with advanced RCC, the genomic make-up in patients with advanced RCC was investigated to identify putative actionable variants and signatures. In this prospective multicenter study (NCT01855477), whole-genome sequencing (WGS) data of locally advanced and metastatic tissue biopsies and matched whole-blood samples were collected from 91 patients with histopathologically confirmed RCC. WGS data were analyzed for small somatic variants, copy-number alterations and structural variants. For a subgroup of patients, RNA sequencing (RNA-Seq) data could be analyzed. RNA-Seq data were clustered on immunogenic and angiogenic gene expression patterns according to a previously developed angio-immunogenic gene signature. In all patients with papillary and clear cell RCC, putative actionable drug targets were detected by WGS, of which 94% were on-label available. RNA-Seq data of clear cell and papillary RCC were clustered using a previously developed angio-immunogenic gene signature. Analyses of driver mutations and RNA-Seq data revealed clear differences among different RCC subtypes, showing the added value of WGS and RNA-Seq over clinicopathological data. By improving both histological subtyping and the selection of treatment according to actionable targets and immune signatures, WGS and RNA-Seq may improve therapeutic decision making for most patients with advanced RCC, including patients with non-clear cell RCC for whom no standard treatment is available to data. Prospective clinical trials are needed to evaluate the impact of genomic and transcriptomic diagnostics on survival outcome for advanced RCC patients.

ESMO-Magnitude of Clinical Benefit Scale for haematological malignancies (ESMO-MCBS:H) version 1.0.

BACKGROUND: The European Society for Medical Oncology (ESMO)-Magnitude of Clinical Benefit Scale (MCBS) has been accepted as a robust tool to evaluate the magnitude of clinical benefit reported in trials for oncological therapies. However, the ESMO-MCBS hitherto has only been validated for solid tumours. With the rapid development of novel therapies for haematological malignancies, we aimed to develop an ESMO-MCBS version that is specifically designed and validated for haematological malignancies. METHODS: ESMO and the European Hematology Association (EHA) initiated a collaboration to develop a version for haematological malignancies (ESMO-MCBS:H). The process incorporated five landmarks: field testing of the ESMO-MCBS version 1.1 (v1.1) to identify shortcomings specific to haematological diseases, drafting of the ESMO-MCBS:H forms, peer review and revision of the draft based on re-scoring (resulting in a second draft), assessment of reasonableness of the scores generated, final review and approval by ESMO and EHA including executive boards. RESULTS: Based on the field testing results of 80 haematological trials and extensive review for feasibility and reasonableness, five amendments to ESMO-MCBS were incorporated in the ESMO-MCBS:H addressing the identified shortcomings. These concerned mainly clinical trial endpoints that differ in haematology versus solid oncology and the very indolent nature of nevertheless incurable diseases such as follicular lymphoma, which hampers presentation of mature data. In addition, general changes incorporated in the draft version of the ESMO-MCBS v2 were included, and specific forms for haematological malignancies generated. Here we present the final approved forms of the ESMO-MCBS:H, including instructions. CONCLUSION: The haematology-specific version ESMO-MCBS:H allows now full applicability of the scale for evaluating the magnitude of clinical benefit derived from clinical studies in haematological malignancies.

Methodological and reporting standards for quality-of-life data eligible for European Society for Medical Oncology-Magnitude of Clinical Benefit Scale (ESMO-MCBS) credit.

BACKGROUND: The European Society for Medical Oncology-Magnitude of Clinical Benefit Scale (ESMO-MCBS) has been developed to grade clinical benefit of cancer therapies. Improvement in quality of life (QoL) is considered relevant, especially in the non-curative setting. This is reflected by an upgrade of the preliminary ESMO-MCBS score if QoL is improved compared to the control arm or a downgrade if an improvement in progression-free survival is not paralleled by an improvement in QoL or overall survival. Given the importance of QoL for the final score, a need to ensure the robustness of QoL data was recognised. DESIGN: A checklist was created based on existing guidelines for QoL research. Field testing was carried out using clinical trials that either received an adjustment of the preliminary ESMO-MCBS score based on QoL or had QoL as the primary endpoint. Several rounds of revision and re-testing of the checklist were undertaken until a final consensus was reached. RESULTS: The final checklist consists of four items and can be applied if three prerequisites are met: (i) QoL is at least a secondary endpoint, (ii) evidence of reliability and validity of the instrument is provided, and (iii) a statistically and clinically significant improvement in QoL is observed. The four items on the checklist pertain to the (i) hypothesis, (ii) compliance and missing data, (iii) presentation of the results, and (iv) statistical and clinical relevance. Field testing revealed that a clear QoL hypothesis and correction for multiple testing were mostly lacking, while the main statistical method was always described. CONCLUSIONS: Implementation of the ESMO-MCBS QoL checklist will facilitate objective and transparent decision making on QoL data within the ESMO-MCBS scoring process. Trials published until 1 January 2025 will have to meet the prerequisites and at least two items for crediting QoL benefit in the final ESMO-MCBS score. Trials published thereafter will have to meet all four items.

Immune checkpoint inhibitor-associated myocarditis : Case reports and a review of the literature.

Immune checkpoint inhibitors (ICIs) are increasingly recognised to effectuate long-lasting therapeutic responses in solid tumours. However, ICI therapy can also result in various immune-related adverse events, such as ICI-associated myocarditis, a rare but serious complication. The clinical spectrum is wide and includes asymptomatic patients and patients with fulminant heart failure, making it challenging to diagnose this condition. Furthermore, the optimal diagnostic algorithm and treatment of ICI-associated myocarditis is unknown. In this review, we describe two cases on both ends of the spectrum and discuss the challenges in recognising, diagnosing and treating ICI-associated myocarditis.

Biases in study design, implementation, and data analysis that distort the appraisal of clinical benefit and ESMO-Magnitude of Clinical Benefit Scale (ESMO-MCBS) scoring.

BACKGROUND: The European Society for Medical Oncology-Magnitude of Clinical Benefit Scale (ESMO-MCBS) is a validated, widely used tool developed to score the clinical benefit from cancer medicines reported in clinical trials. ESMO-MCBS scores assume valid research methodologies and quality trial implementation. Studies incorporating flawed design, implementation, or data analysis may generate outcomes that exaggerate true benefit and are not generalisable. Failure to either indicate or penalise studies with bias undermines the intention and diminishes the integrity of ESMO-MCBS scores. This review aimed to evaluate the adequacy of the ESMO-MCBS to address bias generated by flawed design, implementation, or data analysis and identify shortcomings in need of amendment. METHODS: As part of a refinement of the ESMO-MCBS, we reviewed trial design, implementation, and data analysis issues that could bias the results. For each issue of concern, we reviewed the ESMO-MCBS v1.1 approach against standards derived from Helsinki guidelines for ethical human research and guidelines from the International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use, the Food and Drugs Administration, the European Medicines Agency, and European Network for Health Technology Assessment. RESULTS: Six design, two implementation, and two data analysis and interpretation issues were evaluated and in three, the ESMO-MCBS provided adequate protections. Seven shortcomings in the ability of the ESMO-MCBS to identify and address bias were identified. These related to (i) evaluation of the control arm, (ii) crossover issues, (iii) criteria for non-inferiority, (iv) substandard post-progression treatment, (v) post hoc subgroup findings based on biomarkers, (vi) informative censoring, and (vii) publication bias against quality-of-life data. CONCLUSION: Interpretation of the ESMO-MCBS scores requires critical appraisal of trials to understand caveats in trial design, implementation, and data analysis that may have biased results and conclusions. These will be addressed in future iterations of the ESMO-MCBS.

Evaluating the effects of storage conditions on dry matter loss and nutritional quality of grain legume fodders in West Africa.

Feed scarcity is a major challenge for livestock production in West Africa, especially during the dry season when grass quality and quantity on grazing lands are inadequate. In the dry season, crop residues are a key source of livestock feed. The residues of grain legumes, also known as grain legume fodders (GLFs), are stored and traded for feeding in the dry season. The objectives of our experiment were to evaluate the effects of storage conditions and duration on dry matter (DM) and nutritional quality of GLFs, and to assess the risk of aflatoxin in stored groundnut fodder. The experiment was designed as a factorial trial with 18 treatment combinations with four replicates (4 farms). The treatments included: 3 types of GLFs (cowpea, groundnut and soybean fodder), 3 types of storage locations (rooftop, room and tree-fork) and 2 types of packaging (packed in polythene sacks and unpacked but tied with rope). Over a 120 day storage period, DM quantity reduced by an average of 24 % across all storage conditions, showing a range from 14 % in the best condition (sacks and rooms) to 35 % in the worst condition (bundles tied with rope and stored on rooftops or tree-forks). Soybean fodder had no leaves, the lowest crude protein content (CP) and organic matter digestibility (OMD), and the highest content of cell wall components compared to cowpea and groundnut fodder. These nutritional quality parameters in soybean fodder hardly changed during storage. Cowpea and groundnut fodder showed a decrease in leaf-to-stem ratio (LSR), CP and OMD, and an increase in the content of cell wall components during storage, but their nutritional value remained better than that of soybean fodder. Storage in sacks resulted in less DM loss, in less reduction of LSR and in a smaller increase of the content of cell wall components than storage of bundles tied with rope. Our study shows that the DM loss, the decrease in LSR, and the increase in the content of cell wall components can be prevented partly by storing GLFs in sacks instead of tying bundles with rope, and to a minor extent by storing in rooms instead of in the open air. Aflatoxin was not detectable in the groundnut fodder samples. Our results highlight that attention to storage conditions can improve the feeding value of GLFs which are key for livestock nutrition during the dry season.

Insulin-like factor 3, luteinizing hormone and testosterone in testicular cancer patients: effects of ß-hCG and cancer treatment.

BACKGROUND: Primary hypogonadism (low testosterone and high luteinizing hormone, LH) is present in approximately 20% of testicular cancer (TC) survivors after orchidectomy with or without chemotherapy. OBJECTIVES: We investigated insulin-like factor 3 (INSL3), a novel marker of Leydig cell function, in TC patients. MATERIALS AND METHODS: We analyzed: (I) a cross-sectional cohort of TC patients after orchidectomy with or without chemotherapy (1988-1999) at long-term follow-up (median 36 and 35 years of age at follow-up, respectively) and healthy men of similar age; (II) a longitudinal cohort of chemotherapy-treated TC patients (2000-2008), analyzed before and 1 year after chemotherapy (median 29 years of age at chemotherapy). INSL3, testosterone, and LH were compared between groups and over time and related to pre-chemotherapy ß-hCG levels. RESULTS: In the cross-sectional cohort, TC patients at median 7 years after orchidectomy and chemotherapy (n = 79) had higher LH (p < 0.001), lower testosterone (p = 0.001), but similar INSL3 as controls (n = 40). After orchidectomy only (n = 25), higher LH (p = 0.02), but no differences in testosterone or INSL3 were observed compared to controls. In the longitudinal cohort, patients with normal pre-chemotherapy ß-hCG (≤5 mU/L, n = 35) had increased LH 1 year after chemotherapy compared to pre-chemotherapy (p = 0.001), and no change in testosterone or INSL3. In contrast, patients with high ß-hCG pre-chemotherapy (n = 42) had suppressed LH, markedly elevated testosterone, and low INSL3 at start of chemotherapy, with increased LH, decreased testosterone, and increased INSL3 1 year later (all p < 0.001). DISCUSSION: Changes in LH show that gonadal endocrine function is disturbed before chemotherapy, 1 year later, and at long-term follow-up in chemotherapy-treated TC patients. CONCLUSION: Pre-chemotherapy, ß-hCG-producing tumors affect the gonadal endocrine axis, demonstrated by increased testosterone and decreased LH. INSL3 did not uniformly follow the pattern of testosterone.

LiGAPS-Beef, a mechanistic model to explore potential and feed-limited beef production 2: sensitivity analysis and evaluation of sub-models.

The model LiGAPS-Beef (Livestock simulator for Generic analysis of Animal Production Systems - Beef cattle) has been developed to assess potential and feed-limited growth and production of beef cattle in different areas of the world and to identify the processes responsible for the yield gap. Sensitivity analysis and evaluation of model results with experimental data are important steps after model development. The first aim of this paper, therefore, is to identify which parameters affect the output of LiGAPS-Beef most by conducting sensitivity analyses. The second aim is to evaluate the accuracy of the thermoregulation sub-model and the feed intake and digestion sub-model with experimental data. Sensitivity analysis was conducted using a one-at-a-time approach. The upper critical temperature (UCT) simulated with the thermoregulation sub-model was most affected by the body core temperature and parameters affecting latent heat release from the skin. The lower critical temperature (LCT) and UCT were considerably affected by weather variables, especially ambient temperature and wind speed. Sensitivity analysis for the feed intake and digestion sub-model showed that the digested protein per kg feed intake was affected to a larger extent than the metabolisable energy (ME) content. Sensitivity analysis for LiGAPS-Beef was conducted for ¾ Brahman×» Shorthorn cattle in Australia and Hereford cattle in Uruguay. Body core temperature, conversion of digestible energy to ME, net energy requirements for maintenance, and several parameters associated with heat release affected feed efficiency at the herd level most. Sensitivity analyses have contributed, therefore, to insight which parameters are to be investigated in more detail when applying LiGAPS-Beef. Model evaluation was conducted by comparing model simulations with independent data from experiments. Measured heat production in experiments corresponded fairly well to the heat production simulated with the thermoregulation sub-model. Measured ME contents from two data sets corresponded well to the ME contents simulated with the feed intake and digestion sub-model. The relative mean absolute errors were 9.3% and 6.4% of the measured ME contents for the two data sets. In conclusion, model evaluation indicates the thermoregulation sub-model can deal with a wide range of weather conditions, and the feed intake and digestion sub-model with a variety of feeds, which corresponds to the aim of LiGAPS-Beef to simulate cattle in different beef production systems across the world.

LiGAPS-Beef, a mechanistic model to explore potential and feed-limited beef production 1: model description and illustration.

The expected increase in the global demand for livestock products calls for insight in the scope to increase actual production levels across the world. This insight can be obtained by using theoretical concepts of production ecology. These concepts distinguish three production levels for livestock: potential (i.e. theoretical maximum) production, which is defined by genotype and climate only; feed-limited production, which is limited by feed quantity and quality; and actual production. The difference between the potential or limited production and the actual production is the yield gap. The objective of this paper, the first in a series of three, is to present a mechanistic, dynamic model simulating potential and feed-limited production for beef cattle, which can be used to assess yield gaps. A novelty of this model, named LiGAPS-Beef (Livestock simulator for Generic analysis of Animal Production Systems - Beef cattle), is the identification of the defining factors (genotype and climate) and limiting factors (feed quality and available feed quantity) for cattle growth by integrating sub-models on thermoregulation, feed intake and digestion, and energy and protein utilisation. Growth of beef cattle is simulated at the animal and herd level. The model is designed to be applicable to different beef production systems across the world. Main model inputs are breed-specific parameters, daily weather data, information about housing, and data on feed quality and quantity. Main model outputs are live weight gain, feed intake and feed efficiency (FE) at the animal and herd level. Here, the model is presented, and its use is illustrated for Charolais and Brahman × Shorthorn cattle in France and Australia. Potential and feed-limited production were assessed successfully, and we show that FE of herds is highest for breeds most adapted to the local climate conditions. LiGAPS-Beef also identified the factors that define and limit growth and production of cattle. Hence, we argue the model has scope to be used as a tool for the assessment and analysis of yield gaps in beef production systems.

LiGAPS-Beef, a mechanistic model to explore potential and feed-limited beef production 3: model evaluation.

LiGAPS-Beef (Livestock simulator for Generic analysis of Animal Production Systems - Beef cattle) is a generic, mechanistic model designed to quantify potential and feed-limited growth, which provides insight in the biophysical scope to increase beef production (i.e. yield gap). Furthermore, it enables identification of the bio-physical factors that define and limit growth, which provides insight in management strategies to mitigate yield gaps. The aim of this paper, third in a series of three, is to evaluate the performance of LiGAPS-Beef with independent experimental data. After model calibration, independent data were used from six experiments in Australia, one in Uruguay and one in the Netherlands. Experiments represented three cattle breeds, and a wide range of climates, feeding strategies and cattle growth rates. The mean difference between simulated and measured average daily gains (ADGs) was 137 g/day across all experiments, which equals 20.1% of the measured ADGs. The root mean square error was 170 g/day, which equals 25.0% of the measured ADGs. LiGAPS-Beef successfully simulated the factors that defined and limited growth during the experiments on a daily basis (genotype, heat stress, digestion capacity, energy deficiency and protein deficiency). The simulated factors complied well to the reported occurrence of heat stress, energy deficiency and protein deficiency at specific periods during the experiments. We conclude that the level of accuracy of LiGAPS-Beef is acceptable, and provides a good basis for acquiring insight in the potential and feed-limited production of cattle in different beef production systems across the world. Furthermore, its capacity to identify factors that define or limit growth and production provides scope to use the model for yield gap analysis.

Closing the phosphorus cycle in a food system: insights from a modelling exercise.

Mineral phosphorus (P) used to fertilise crops is derived from phosphate rock, which is a finite resource. Preventing and recycling mineral P waste in the food system, therefore, are essential to sustain future food security and long-term availability of mineral P. The aim of our modelling exercise was to assess the potential of preventing and recycling P waste in a food system, in order to reduce the dependency on phosphate rock. To this end, we modelled a hypothetical food system designed to produce sufficient food for a fixed population with a minimum input requirement of mineral P. This model included representative crop and animal production systems, and was parameterised using data from the Netherlands. We assumed no import or export of feed and food. We furthermore assumed small P soil losses and no net P accumulation in soils, which is typical for northwest European conditions. We first assessed the minimum P requirement in a baseline situation, that is 42% of crop waste is recycled, and humans derived 60% of their dietary protein from animals (PA). Results showed that about 60% of the P waste in this food system resulted from wasting P in human excreta. We subsequently evaluated P input for alternative situations to assess the (combined) effect of: (1) preventing waste of crop and animal products, (2) fully recycling waste of crop products, (3) fully recycling waste of animal products and (4) fully recycling human excreta and industrial processing water. Recycling of human excreta showed most potential to reduce P waste from the food system, followed by prevention and finally recycling of agricultural waste. Fully recycling P could reduce mineral P input by 90%. Finally, for each situation, we studied the impact of consumption of PA in the human diet from 0% to 80%. The optimal amount of animal protein in the diet depended on whether P waste from animal products was prevented or fully recycled: if it was, then a small amount of animal protein in the human diet resulted in the most sustainable use of P; but if it was not, then the most sustainable use of P would result from a complete absence of animal protein in the human diet. Our results apply to our hypothetical situation. The principles included in our model however, also hold for food systems with, for example, different climatic and soil conditions, farming practices, representative types of crops and animals and population densities.

Influence of distance to urban markets on smallholder dairy farming systems in Kenya.

We studied influence of distance to urban markets on smallholder dairy farming system development. Farms were chosen from three locations that varied in distance to the urban market of Nakuru Town in the Kenyan highlands: urban location (UL, n = 10) at less than 15 km distance, mid-rural location (MRL, n = 11) in between 20 and 50 km west of Nakuru and extreme rural location (ERL, n = 9) beyond 50 km west and south-west of Nakuru. In-depth interviews with farmers and focus group discussions with eight groups of stakeholders were held to collect narratives and data about market quality, production factors, farm performance and functions of dairy cattle. We applied thematic content analysis to qualitative information by clustering narratives according to predefined themes and used ANOVA to analyse farm data. In UL, markets were functional, with predominantly informal market chains, with a high milk price (US $ 45.1/100 kg). Inputs were available in UL markets, but prices were high for inputs such as concentrates, fodder, replacement stock and hired labour. Moreover, availability of grazing land and the high opportunity costs for family labour were limiting dairy activities. In UL, milk production per cow (6.9 kg/cow/day) and per farm (20.1 kg/farm/day) were relatively low, and we concluded that farm development was constrained by scarcity of inputs and production factors. In rural locations (MRL and ERL), markets were functional with relatively low prices (average US $ 32.8/100 kg) for milk in both formal and informal market chains. Here, concentrates were relatively cheap but also of low quality. Fodder, replacement stock and labour were more available in rural locations than in UL. In rural locations, milk production per cow (average 7.2 kg/cow/day) and per farm (average 18.5 kg/farm/day) were low, and we concluded that farm development was constrained by low quality of concentrates and low price of milk. In all locations, production for subsistence was valued since income generated was used for non-dairy expenses. A tailor-made package of interventions that targets the above constraints is recommended for farm development.

Traditional ecological knowledge underlying herding decisions of pastoralists.

Pastoralists have traditional ecological knowledge (TEK), which is important for their livelihoods and for policies and interventions. Pastoralism is under pressure, however, which may result in a decline of pastoral lifestyle and its related TEK. We, therefore, addressed the following objectives (i) to inventorise and assess how pastoralists characterise and value soils and forages in their environment, (ii) to analyse how soil, forage and livestock (i.e. cattle) characteristics relate to herding decisions and (iii) to determine whether TEK underlying herding decisions differs across generations. Data were collected through focus groups and individual interviews with 72 pastoralists, belonging to three generations and to three agro-ecological zones. Using a three-point scale (high, medium, low), four grasses and three tree forages were assessed in terms of nutritional quality for milk, meat, health and strength. Using their own visual criteria, pastoralists identified five different soils, which they selected for herding at different times of the year. Pastoralists stated that Pokuri was the best soil because of its low moisture content, whereas Karaal was the worst because forage hardly grows on it. They stated that perennials, such as Andropogon gayanus and Loxoderra ledermannii, were of high nutritional quality, whereas annuals such as Andropogon pseudapricus and Hyparrhenia involucrata were of low nutritional quality. Afzelia africana was perceived of high quality for milk production, whereas Khaya senegalensis had the highest quality for meat, health and strength. Pastoralists first used soil, then forage and finally livestock characteristics in their herding decisions. Pastoralists' TEK was not associated with their generations, but with their agro-ecological zones. This study suggests that pastoralists had common and detailed TEK about soils, forages and livestock characteristics, underlying their herding decisions. To conclude, pastoralists use a holistic approach, combining soil, vegetation and livestock TEK in herding decisions. Such TEK can guide restoration or improvement of grazing lands, and land use planning.

Systemic therapies for recurrent or metastatic nasopharyngeal carcinoma: a systematic review.

BACKGROUND: The majority of published studies in recurrent or metastatic nasopharyngeal carcinoma (RM-NPC) are single-arm trials. Reliable modelling of progression-free survival (PFS) and overall survival (OS) outcomes, therefore, is difficult. This study aim to analyse existent literature to estimate the relative efficacy of available systemic regimens in RM-NPC, as well as provide estimates of aggregate OS and PFS. METHODS: We conducted a systematic search of MEDLINE, EMBASE and the Cochrane Library to March 2015. Clinical trials (in English only) investigating cytotoxic and molecularly targeted agents in adult patients with RM-NPC were included. All relevant studies were assessed for quality using Downs and Blacks (DB) checklist (maximum quality score of 27). Aggregate data analysis and Student's t-test were performed for all identified studies (model A). For studies that published analysable Kaplan-Meier curves, survival data were extracted and marginal proportional hazards models were constructed (model B). RESULTS: A total of 56 studies were identified and included in model A, 26 of which had analysable Kaplan-Meier curves and were included in model B. The 26 studies in model B had significantly higher mean DB scores than the remaining 30 (17.3 vs 13.7, P=0.002). For patients receiving first line chemotherapy, the estimated median OS was 15.7 months by model A (95% CI, 12.3-19.1), and 19.3 months by model B (95% CI, 17.6-21.1). For patients undergoing second line or higher therapies (2nd+), the estimated median OS was 11.5 months by model A (95% CI 10.1-12.9), and 12.5 months by model B (95% CI 11.9-13.4). PFS estimates for patients undergoing first-line chemotherapy by model A was 7.6 months (95% CI, 6.2-9.0), and 8.0 months by model B (95% CI, 7.6-8.8). For patients undergoing therapy in the 2nd+ setting, the estimated PFS by model A was 5.4 months (95% CI, 3.8-7.0), and 5.2 months by model B (95% CI, 4.7-5.6). CONCLUSIONS: We present the first aggregate estimates of OS and PFS for RM-NPC patients receiving first and second-line or higher treatment settings, which could inform the design of future clinical trials in this disease setting.

Characterisation of adopters and non-adopters of dairy technologies in Ethiopia and Kenya.

While there is a general consensus that using dairy technologies, such as improved breeds of dairy cows, can substantially increase farm productivity and income, adoption of such technologies has been generally low in developing countries. The underlying reasons for non-adoption of beneficial technologies in the dairy sector are not fully understood. In this study, we characterised adopters and non-adopters of dairy technologies in Ethiopia and Kenya based on farmers' resources ownership in order to identify why many farmers in Ethiopia and Kenya have not adopted improved dairy technologies. As compared to non-adopters, farmers who adopt dairy technology own relatively more farm resources. The result signals that differences in resource endowments could lead to divergent technology adoption scenarios. Results show that a higher proportion of sample smallholders in Kenya have adopted dairy technologies than those in Ethiopia. Except for the use of veterinary services, fewer than 10% of sample farmers in Ethiopia have adopted dairy technologies-less than half the number of adopters in Kenya. The higher level of dairy technology adoption in Kenya can be ascribed partly to the long history of dairy development, including improvements in the value chain for the delivery of inputs, services and fluid milk marketing. Interventions that deal with the constraints related to access to farm resources and input and output markets could facilitate uptake of dairy technology in developing countries.

Clinical outcome of salvage neck dissections in head and neck cancer in relation to initial treatment, extent of surgery and patient factors.

OBJECTIVE: Salvage surgery has a higher complication rate compared to primary surgical treatment. We evaluated clinical outcome of salvage neck dissections in relation to initial treatment modality, extent of surgery and patient-related factors. DESIGN: Single institution consecutive case series. SETTING: Tertiary Head and Neck Cancer Centre. PARTICIPANTS: In all, 87 patients with head and neck squamous cell carcinoma, who underwent salvage neck dissection after initial radiotherapy (n = 30), radiotherapy with carboplatin/5-fluorouracil (n = 43) or radiotherapy with cetuximab (n = 14). MAIN OUTCOME MEASURES: Incidence of complications, disease-specific survival. RESULTS: Complications occurred in 28% of the patients. Multivariate analysis identified extent of neck dissection as the only independent predictor of surgical complications (P = 0.010). Surgical complication rate was 16% after radiotherapy with systemic treatment, and 47% after radiotherapy alone (P = 0.171). The 5-year disease-specific survival was 55%, independent of complications, initial treatment, extent of surgery and patient-related factors. CONCLUSION: The only predictor for surgical complications was extent of surgery. Survival was not influenced by complications.

[Docetaxel for metastatic prostate cancer: early is better]. / Docetaxel voor gemetastaseerd prostaatcarcinoom.

Androgen deprivation therapy (ADT) has been used to treat patients with metastatic prostate cancer for many years. Docetaxel chemotherapy administered to patients with metastatic castrate-resistant prostate cancer has been standard since 2004 with a modest survival benefit. Recent data from two randomised studies (CHAARTED and STAMPEDE) demonstrate that combining ADT with docetaxel in men with hormone-naïve metastatic prostate cancer resulted in an impressive overall survival benefit of more than a year as compared with ADT alone. In a meta-analysis, the consistency of these data was confirmed. On the basis of these data, addition of six 3-weekly courses of docetaxel to ADT should be considered as standard treatment in chemo-fit patients with hormone-naïve metastatic prostate cancer.