Improved maximum likelihood estimators in a heteroskedastic errors-in-variables model

This paper develops a bias correction scheme for a multivariate heteroskedastic errors-in-variables model. The applicability of this model is justified in areas such as astrophysics, epidemiology and analytical chemistry, where the variables are subject to measurement errors and the variances vary with the observations. We conduct Monte Carlo simulations to investigate the performance of the corrected estimators. The numerical results show that the bias correction scheme yields nearly unbiased estimates. We also give an application to a real data set.Comment: 12 pages. Statistical Paper

Oral tolerance to cancer can be abrogated by T regulatory cell inhibition

Oral administration of tumour cells induces an immune hypo-responsiveness known as oral tolerance. We have previously shown that oral tolerance to a cancer is tumour antigen specific, non-cross-reactive and confers a tumour growth advantage. We investigated the utilisation of regulatory T cell (Treg) depletion on oral tolerance to a cancer and its ability to control tumour growth. Balb/C mice were gavage fed homogenised tumour tissue – JBS fibrosarcoma (to induce oral tolerance to a cancer), or PBS as control. Growth of subcutaneous JBS tumours were measured; splenic tissue excised and flow cytometry used to quantify and compare systemic Tregs and T effector (Teff) cell populations. Prior to and/or following tumour feeding, mice were intraperitoneally administered anti-CD25, to inactivate systemic Tregs, or given isotype antibody as a control. Mice which were orally tolerised prior to subcutaneous tumour induction, displayed significantly higher systemic Treg levels (14% vs 6%) and faster tumour growth rates than controls (p<0.05). Complete regression of tumours were only seen after Treg inactivation and occurred in all groups - this was not inhibited by tumour feeding. The cure rates for Treg inactivation were 60% during tolerisation, 75% during tumour growth and 100% during inactivation for both tolerisation and tumour growth. Depletion of Tregs gave rise to an increased number of Teff cells. Treg depletion post-tolerisation and post-tumour induction led to the complete regression of all tumours on tumour bearing mice. Oral administration of tumour tissue, confers a tumour growth advantage and is accompanied by an increase in systemic Treg levels. The administration of anti-CD25 Ab decreased Treg numbers and caused an increase in Teffs. Most notably Treg cell inhibition overcame established oral tolerance with consequent tumor regression, especially relevant to foregut cancers where oral tolerance is likely to be induced by the shedding of tumour tissue into the gut

Summer weather becomes more persistent in a 2 °C world

Heat and rainfall extremes have intensified over the past few decades and this trend is projected to continue with future global warming1–3. A long persistence of extreme events often leads to societal impacts with warm-and-dry conditions severely affecting agriculture and consecutive days of heavy rainfall leading to flooding. Here we report systematic increases in the persistence of boreal summer weather in a multi-model analysis of a world 2 °C above pre-industrial compared to present-day climate. Averaged over the Northern Hemisphere mid-latitude land area, the probability of warm periods lasting longer than two weeks is projected to increase by 4% (2–6% full uncertainty range) after removing seasonal-mean warming. Compound dry–warm persistence increases at a similar magnitude on average but regionally up to 20% (11–42%) in eastern North America. The probability of at least seven consecutive days of strong precipitation increases by 26% (15–37%) for the mid-latitudes. We present evidence that weakening storm track activity contributes to the projected increase in warm and dry persistence. These changes in persistence are largely avoided when warming is limited to 1.5 °C. In conjunction with the projected intensification of heat and rainfall extremes, an increase in persistence can substantially worsen the effects of future weather extremes

Ghrelin Indirectly Activates Hypophysiotropic CRF Neurons in Rodents

Ghrelin is a stomach-derived hormone that regulates food intake and neuroendocrine function by acting on its receptor, GHSR (Growth Hormone Secretagogue Receptor). Recent evidence indicates that a key function of ghrelin is to signal stress to the brain. It has been suggested that one of the potential stress-related ghrelin targets is the CRF (Corticotropin-Releasing Factor)-producing neurons of the hypothalamic paraventricular nucleus, which secrete the CRF neuropeptide into the median eminence and activate the hypothalamic-pituitary-adrenal axis. However, the neural circuits that mediate the ghrelin-induced activation of this neuroendocrine axis are mostly uncharacterized. In the current study, we characterized in vivo the mechanism by which ghrelin activates the hypophysiotropic CRF neurons in mice. We found that peripheral or intra-cerebro-ventricular administration of ghrelin strongly activates c-fos – a marker of cellular activation – in CRF-producing neurons. Also, ghrelin activates CRF gene expression in the paraventricular nucleus of the hypothalamus and the hypothalamic-pituitary-adrenal axis at peripheral level. Ghrelin administration directly into the paraventricular nucleus of the hypothalamus also induces c-fos within the CRF-producing neurons and the hypothalamic-pituitary-adrenal axis, without any significant effect on the food intake. Interestingly, dual-label immunohistochemical analysis and ghrelin binding studies failed to show GHSR expression in CRF neurons. Thus, we conclude that ghrelin activates hypophysiotropic CRF neurons, albeit indirectly

Living Invisible: HTLV-1-Infected Persons and the Lack of Care in Public Health

Human T-cell lymphotropic virus type 1 (HTLV-1) infection is commonly confounded with Human Immunodeficiency Virus (HIV) infection and it is unknown to many health professionals. It is endemic in many countries and there is no effective treatment available. Although a few individuals have severe symptoms, most patients remain asymptomatic throughout their lives. Further, HTLV-1 is considered a neglected public health problem and limited studies cover specific patients' needs and emotional experiences. To better understand how women and men living with HTLV-1 experience the disease and what issues exist in their healthcare processes, we conducted a qualitative study of both symptomatic and asymptomatic patients at an outpatient clinic at the Emílio Ribas Infectious Diseases Institute in São Paulo, Brazil. We found that the main focus of health staff was on illness risk, but not identifying infected relatives and preventing new infections. This point of view, ultimately neglected patients' complex demands, and overshadows the prevention of new infections and contributes to the lack of care in public health for HTLV-1 infected subjects. Furthermore, this perpetuates the infection among these populations and the patients experience an “invisibility” of their specific needs, such as reproductive rights and feel that their rights as citizens are ignored

Temporal changes in phytoplankton biomass and cellular properties; implications for the IMO Ballast Water Convention

In the Wadden Sea, the Netherlands, and at L4 in the English Channel, UK, the size class distribution of phytoplankton was investigated with respect to the size range >10–≤50 µm identified by the IMO Ballast Water Convention. Size fractionation using 10 µm mesh filtration showed considerable size bias; 23.1% of >10 µm cells were still present in the 10–≤50 µm size, these were on average 3.6% and 2% in the Wadden Sea and at L4, respectively. In terms of chlorophyll biomass, they represented 28.7% and 12%, respectively. The filtration method resulted in much higher chlorophyll values for 10–50  µm size range: 53.7% in the Wadden Sea and 38% at L4. This overestimation appears to be caused by cells in 6–10  µm size range being retained on the mesh. These findings are relevant in the context of the size class distribution based on flowcytometry and semi-quantification using chlorophyll as proxy for cell density