High-dose alkylating chemotherapy in BRCA-altered triple-negative breast cancer:the randomized phase III NeoTN trial

Exploratory analyses of high-dose alkylating chemotherapy trials have suggested that BRCA1 or BRCA2-pathway altered (BRCA-altered) breast cancer might be particularly sensitive to this type of treatment. In this study, patients with BRCA-altered tumors who had received three initial courses of dose-dense doxorubicin and cyclophosphamide (ddAC), were randomized between a fourth ddAC course followed by high-dose carboplatin-thiotepa-cyclophosphamide or conventional chemotherapy (initially ddAC only or ddAC-capecitabine/decetaxel [CD] depending on MRI response, after amendment ddAC-carboplatin/paclitaxel [CP] for everyone). The primary endpoint was the neoadjuvant response index (NRI). Secondary endpoints included recurrence-free survival (RFS) and overall survival (OS). In total, 122 patients were randomized. No difference in NRI-score distribution (p = 0.41) was found. A statistically non-significant RFS difference was found (HR 0.54; 95% CI 0.23–1.25; p = 0.15). Exploratory RFS analyses showed benefit in stage III (n = 35; HR 0.16; 95% CI 0.03–0.75), but not stage II (n = 86; HR 1.00; 95% CI 0.30–3.30) patients. For stage III, 4-year RFS was 46% (95% CI 24–87%), 71% (95% CI 48–100%) and 88% (95% CI 74–100%), for ddAC/ddAC-CD, ddAC-CP and high-dose chemotherapy, respectively. No significant differences were found between high-dose and conventional chemotherapy in stage II-III, triple-negative, BRCA-altered breast cancer patients. Further research is needed to establish if there are patients with stage III, triple negative BRCA-altered breast cancer for whom outcomes can be improved with high-dose alkylating chemotherapy or whether the current standard neoadjuvant therapy including carboplatin and an immune checkpoint inhibitor is sufficient. Trial Registration: NCT01057069

Constraints on Energy Intake in Fish: The Link between Diet Composition, Energy Metabolism, and Energy Intake in Rainbow Trout

The hypothesis was tested that fish fed to satiation with iso-energetic diets differing in macronutrient composition will have different digestible energy intakes (DEI) but similar total heat production. Four iso-energetic diets (2×2 factorial design) were formulated having a contrast in i) the ratio of protein to energy (P/E): high (HP/E) vs. low (LP/E) and ii) the type of non-protein energy (NPE) source: fat vs. carbohydrate which were iso-energetically exchanged. Triplicate groups (35 fish/tank) of rainbow trout were hand-fed each diet twice daily to satiation for 6 weeks under non-limiting water oxygen conditions. Feed intake (FI), DEI (kJ kg−0.8 d−1) and growth (g kg−0.8 d−1) of trout were affected by the interaction between P/E ratio and NPE source of the diet (P<0.05). Regardless of dietary P/E ratio, the inclusion of carbohydrate compared to fat as main NPE source reduced DEI and growth of trout by ∼20%. The diet-induced differences in FI and DEI show that trout did not compensate for the dietary differences in digestible energy or digestible protein contents. Further, changes in body fat store and plasma glucose did not seem to exert a homeostatic feedback control on DEI. Independent of the diet composition, heat production of trout did not differ (P>0.05). Our data suggest that the control of DEI in trout might be a function of heat production, which in turn might reflect a physiological limit related with oxidative metabolism

Dietary electrolyte balance affects the nutrient digestibility and maintenance energy expenditure of Nile tilapia

Acid-base disturbances caused by environmental factors and physiological events including feeding have been well documented in several fish species, but little is known about the impact of dietary electrolyte balance (dEB). In the present study, we investigated the effect of feeding diets differing in dEB (2100, 200, 500 or 800 mEq/kg diet) on the growth, nutrient digestibility and energy balance of Nile tilapia. After 5 weeks on the test diet, the growth of the fish was linearly affected by the dEB levels (P < 0.001), with the lowest growth being observed in the fish fed the 800 dEB diet. The apparent digestibility coefficient (ADC) of fat was unaffected by dEB, whereas the ADC of DM and protein were curvilinearly related to the dEB levels, being lowest and highest in the 200 and 800 dEB diets, respectively. Stomach chyme pH at 3 h after feeding was linearly related to the dEB levels (P < 0.05). At the same time, blood pH of the heart (P < 0.05) and caudal vein (P < 0.01) was curvilinearly related to the dEB levels, suggesting the influence of dEB on postprandial metabolic alkalosis. Consequently, maintenance energy expenditure (MEm) was curvilinearly related to the dEB levels (P < 0.001), being 54% higher in the 800 dEB group (88 kJ/kg 0.8 per d) than in the 200 dEB group (57 kJ/kg 0.8 per d). These results suggest that varying dEB levels in a diet have both positive and negative effects on fish. On the one hand, they improve nutrient digestibility; on the other hand, they challenge the acid-base homeostasis (pH) of fish, causing an increase in MEm, and thereby reduce the energy required for growth

Optimising early youngstock management

The period from birth to first calving for a dairy heifer has not always received much attention on dairy farms, but success in this non-productive period is key to ensuring a profitable system of replacements. For calving at the optimum time of 24 months, growth must be on target and disease incidence must be minimised. This article covers aspects of management that influence growth and disease in this period; starting with colostrum management and success of passive transfer, then feeding of milk and other requirements pre-weaning, optimum housing for disease prevention, through to timing of first service. It is also crucial to record, monitor and assess the success of this period, and practical and applicable methods to do this on farm are discussed

Efetividade do Forward Guidance no mercado de juros dos EUA no período 2009-2016

Esse trabalho tem como objetivo principal investigar se a ferramenta de política monetária não convencional, conhecida como forward guidance, teve o poder de afetar o mercado de juros de títulos públicos dos EUA no período entre 2009 e 2016. Para tal, será feita a comparação entre a variação de preços do mercado de títulos públicos emitidos pelo Tesouro dos EUA após o uso dessa ferramenta contra o restante dos pontos observados. Esse trabalho procura também explicar o funcionamento de ferramentas de política monetária utilizadas por bancos centrais, assim como detalhar cada categoria de forward guidance existente. Concluiu-se que a ferramenta forward guidance afetou o nível de preços do mercado de juros dos EUA, em intensidades diferentes dependendo da categoria utilizada.The main goal of this paper is to investigate if the unconventional monetary policy tool, known as forward guidance, had the power to affect the US treasury securities’ market prices in the years between 2009 and 2016. With that objective in mind, the comparison between fluctuations of the daily treasury yield curve rates after usages of such tool and the remainder of the observed data points will be made. This paper also seeks to explain how conventional monetary policy tools work, as well as to detail each category of forward guidance in existence. It concludes that the forward guidance tool did affect the rates of the treasury yield curve, with varying intensities depending on the category utilized