Obestatin induces testosterone secretion from rat testis in vitro

In this study, the effect of obestatin (23 amino acid peptide) on testosterone secretion in vitro, in the rat testis was observed. For this purpose, two different doses of obestatin (10-9 M and 10-8 M) were used alone and in combination with human chorionic gonadotropin (hCG) in fasting and fed conditions in two age groups. Fasting induced a significant reduction in body weight (p < 0.05) and plasma testosterone concentrations (0.001). hCG stimulated testosterone secretions were significantly (p < 0.05) high as compared to the basal control testosterone concentrations after 90 min in some groups and 180 min of incubation in all groups. Obestatin at the dose of 10-9 M alone and in combination with hCG failed to change testosterone concentrations in all groups; however, 10-8 M obestatin significantly (p < 0.05) induced hCG stimulated testosterone concentrations in both normally fed pre-pubertal and adult rats. No significant difference was noticed in 48 h fasted groups. This data suggests that, obestatin is a positive modulator of testosterone secretion and its effect depends upon the nutritional status of the body.Key words: Obestatin, testosterone, rats, in vitro

Impaired bone marrow homing of cytokine-activated CD34⁺ cells in the NOD/SCID model

The reduced engraftment potential of hematopoietic stem/progenitor cells (HSPCs) after exposure to cytokines may be related to the impaired homing ability of actively cycling cells. We tested this hypothesis by quantifying the short-term horning of human adult CD34+ cells in nonobese diabetic/severe combined immunodeficient (NOD/SCID) animals. We show that the loss of engraftment ability of cytokine-activated CD34+ cells is associated with a reduction in homing of colony-forming cells (CFCs) to bone marrow (BM) at 24 hours after transplantation (from median 2.8% [range, 1.9%-6.1%] to 0.3% [0.0%-0.7%]; n = 3; P < .01), coincident with an increase in CFC accumulation in the lungs (P < .01). Impaired BM homing of cytokine-activated cells was not restored by using sorted cells in G 0G1 or by inducing cell cycle arrest at the G 1/S border. Blocking Fas ligation in vivo did not increase the BM homing of cultured cells. Finally, we tested cytokine combinations or culture conditions previously reported to restore the engraftment of cultured cells but did not find that any of these was able to reverse the changes in homing behavior of cytokine-exposed cells. We suggest that these changes in homing and, as a consequence, engraftment result from the increased migratory capacity of infused activated cells, leading to the loss of selectivity of the homing process. © 2004 by The American Society of Hematology

Assessment of the feasibility of an ultra-low power, wireless digital patch for the continuous ambulatory monitoring of vital signs.

BACKGROUND AND OBJECTIVES: Vital signs are usually recorded at 4–8 h intervals in hospital patients, and deterioration between measurements can have serious consequences. The primary study objective was to assess agreement between a new ultra-low power, wireless and wearable surveillance system for continuous ambulatory monitoring of vital signs and a widely used clinical vital signs monitor. The secondary objective was to examine the system's ability to automatically identify and reject invalid physiological data. SETTING: Single hospital centre. PARTICIPANTS: Heart and respiratory rate were recorded over 2 h in 20 patients undergoing elective surgery and a second group of 41 patients with comorbid conditions, in the general ward. OUTCOME MEASURES: Primary outcome measures were limits of agreement and bias. The secondary outcome measure was proportion of data rejected. RESULTS: The digital patch provided reliable heart rate values in the majority of patients (about 80%) with normal sinus rhythm, and in the presence of abnormal ECG recordings (excluding aperiodic arrhythmias such as atrial fibrillation). The mean difference between systems was less than ±1 bpm in all patient groups studied. Although respiratory data were more frequently rejected as invalid because of the high sensitivity of impedance pneumography to motion artefacts, valid rates were reported for 50% of recordings with a mean difference of less than ±1 brpm compared with the bedside monitor. Correlation between systems was statistically significant (p<0.0001) for heart and respiratory rate, apart from respiratory rate in patients with atrial fibrillation (p=0.02). CONCLUSIONS: Overall agreement between digital patch and clinical monitor was satisfactory, as was the efficacy of the system for automatic rejection of invalid data. Wireless monitoring technologies, such as the one tested, may offer clinical value when implemented as part of wider hospital systems that integrate and support existing clinical protocols and workflows

Sequential Extensions of Causal and Evidential Decision Theory

Moving beyond the dualistic view in AI where agent and environment are separated incurs new challenges for decision making, as calculation of expected utility is no longer straightforward. The non-dualistic decision theory literature is split between causal decision theory and evidential decision theory. We extend these decision algorithms to the sequential setting where the agent alternates between taking actions and observing their consequences. We find that evidential decision theory has two natural extensions while causal decision theory only has one.Comment: ADT 201

Author Correction: Analysis of mutations in pncA reveals non-overlapping patterns among various lineages of Mycobacterium tuberculosis.

A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has not been fixed in the paper

Everybody Needs Somebody Sometimes: Validation of Adaptive Recovery in Robotic Space Operations

This work assesses an adaptive approach to fault recovery in autonomous robotic space operations, which uses indicators of opportunity, such as physiological state measurements and observations of past human assistant performance, to inform future selections. We validated our reinforcement learning approach using data we collected from humans executing simulated mission scenarios. We present a method of structuring humanfactors experiments that permits collection of relevant indicator of opportunity and assigned assistance task performance data, as well as evaluation of our adaptive approach, without requiring large numbers of test subjects. Application of our reinforcement learning algorithm to our experimental data shows that our adaptive assistant selection approach can achieve lower cumulative regret compared to existing non-adaptive baseline approaches when using real human data. Our work has applications beyond space robotics to any application where autonomy failures may occur that require external intervention

Neoadjuvant chemotherapy and trastuzumab versus neoadjuvant chemotherapy followed by post-operative trastuzumab for patients with HER2-positive breast cancer

Neoadjuvant chemotherapy plus trastuzumab (NCT) increases the rate of pathological complete response (pCR) and event-free survival (EFS) compared to neoadjuvant chemotherapy (NC) alone in women with HER2 positive breast cancer (BC). pCR in this setting is associated with improved EFS. Whether NCT preferentially improves EFS in comparison to NC followed by adjuvant trastuzumab initiated postoperatively (NCAT) has not been addressed. Using clinical data from women with HER2 positive BC treated at 7 European institutions between 2007 and 2010 we sought to investigate the impact on breast cancer outcomes of concomitant (NCT) versus sequential (NCAT) treatment in HER2 positive early BC. The unadjusted hazard ratio (HR) for event free survival with NCT compared with NCAT was 0.63 (95% CI 0.37–1.08; p = 0.091). Multivariable analysis revealed that treatment group, tumour size and ER status were significantly associated with EFS from diagnosis. In the whole group NCT was associated with a reduced risk of an event relative to NCAT, an effect that was confined to ER negative (HR: 0.25; 95% CI, 0.10–0.62; p = 0.003) as opposed to ER positive tumours (HR: 1.07; 95% CI, 0.46–2.52; p = 0.869). HER2 positive/ER negative BC treated with NC gain greatest survival benefit when trastuzumab is administered in both the neoadjuvant and adjuvant period rather than in the adjuvant period alone. These data support the early introduction of targeted combination therapy in HER2 positive/ER negative BC

Patient-reported outcomes: pathways to better health, better services, and better societies

This is the author accepted manuscript. The final version is available from the publisher via the DOI in this recordWhile the use of PROs in research is well established, many challenges lie ahead as their use is extended to other applications. There is consensus that health outcome evaluations that include PROs along with clinician-reported outcomes and administrative data are necessary to inform clinical and policy decisions. The initiatives presented in this paper underline evolving recognition that PROs play a unique role in adding the patient perspective alongside clinical (e.g., blood pressure) and organizational (e.g., admission rates) indicators for evaluating the effects of new products, selecting treatments, evaluating quality of care, and monitoring the health of the population. In this paper, we first explore the use of PRO measures to support drug approval and labeling claims. We critically evaluate the evidence and challenges associated with using PRO measures to improve healthcare delivery at individual and population levels. We further discuss the challenges associated with selecting from the abundance of measures available, opportunities afforded by agreeing on common metrics for constructs of interest, and the importance of establishing an evidence base that supports integrating PRO measures across the healthcare system to improve outcomes. We conclude that the integration of PROs as a key end point within individual patient care, healthcare organization and program performance evaluations, and population surveillance will be essential for evaluating whether increased healthcare expenditure is translating into better health outcomes.Jose M. Valderas was supported by an NIHR Clinician Scientist Award (NIHR/CS/010/024)