Comparing treatment fidelity between study arms of a randomized controlled clinical trial for stroke family caregivers

OBJECTIVE: To compare treatment fidelity among treatment arms in the Telephone Assessment and Skill-Building Kit study for stroke caregivers (TASK II) with respect to: 1) protocol adherence; 2) intervention dosage and 3) nurse intervener perspectives. DESIGN: A randomized controlled clinical trial design. SETTING: Urban, community, midwestern United States. SUBJECTS: A total of 254 stroke caregivers (mean ±SD age, 54.4 ±11.8 years), 55 (22.0%) males and 199 (78.4%) females) randomized to the TASK II intervention (n=123) or an Information, Support, and Referral comparison group (n=131). INTERVENTIONS: TASK II participants received the TASK II Resource Guide; Information, Support, and Referral participants received a standard caregiver brochure. At approximately 8 weeks after discharge, both groups received 8 weekly calls from a nurse, with a booster call 4 weeks later. MEASURES: Protocol adherence was evaluated with the TASK II Checklist for Monitoring Adherence. Intervention dosage was measured by the number of minutes caregivers spent reading materials and talking with the nurse. Nurse intervener perspectives were obtained through focus groups. RESULTS: Protocol adherence was 80% for the TASK II and 92% for the Information, Support, and Referral. As expected, intervention dosage differed between TASK II and Information, Support, and Referral with respect to caregiver time spent reading materials (t=-6.49; P<.001) and talking with the nurse (t=-7.38; P<.001). Focus groups with nurses yielded further evidence for treatment fidelity and recommendations for future trials. CONCLUSIONS: These findings substantiate treatment fidelity in both study arms of the TASK II stroke caregiver intervention trial (NIH R01NR010388; ClinicalTrials.govNCT01275495)

Is there a special mechanism behind the changes in somatic cell and polymorphonuclear leukocyte counts, and composition of milk after a single prolonged milking interval in cows?

<p>Abstract</p> <p>Background</p> <p>A single prolonged milking interval (PMI) e.g. after a technical stop in an automated milking system is of concern for the producer since it is associated with a short-lasting increase in milk somatic cell count (SCC), which is a major quality criterion used at the dairy plants. The content of polymorphonuclear leukocytes (PMN) and how the milk quality is influenced has not been much investigated. The SCC peak occurs without any obvious antigen challenge, possibly indicating a different leukocyte attraction mechanism after a PMI than we see during mastitis.</p> <p>Methods</p> <p>Composite cow milk samples were taken at the milkings twice daily during 7 days before and 5 days after a PMI of 24 h. Milk was analyzed for SCC, PMN, fat, protein and lactose, and at some occasions also casein and free fatty acids (FFA).</p> <p>Results</p> <p>During the PMI the proportion of milk PMN increased sharply in spite of marginally increased SCC. The peak SCC was not observed until the second milking after the PMI, in the afternoon day 1. However, the peak SCC value in <it>morning </it>milk did not occur until one day later, concomitantly with a <it>decrease </it>in the proportion of PMN. After declining, SCC still remained elevated while PMN proportion was decreased throughout the study as was also the milk yield, after the first accumulation of milk during the PMI. Milk composition was changed the day after the PMI, (increased fat and protein content; decreased lactose, whey protein and FFA content) but the changes in the following days were not consistent except for lactose that remained decreased the rest of the study.</p> <p>Conclusion</p> <p>The PMI resulted in increased SCC and proportion of PMN. Additionally, it gave rise to minor alterations in the milk composition in the following milkings but no adverse effect on milk quality was observed. The recruitment of PMN, which was further enhanced the first day <it>after </it>the PMI, appeared to be independent of milk volume or accumulation of milk per se. Hence, we suggest that there is a special immunophysiological/chemoattractant background to the increased migration of leukocytes into the milk compartment observed during and after the PMI.</p

Patterns of Ancestry, Signatures of Natural Selection, and Genetic Association with Stature in Western African Pygmies

African Pygmy groups show a distinctive pattern of phenotypic variation, including short stature, which is thought to reflect past adaptation to a tropical environment. Here, we analyze Illumina 1M SNP array data in three Western Pygmy populations from Cameroon and three neighboring Bantu-speaking agricultural populations with whom they have admixed. We infer genome-wide ancestry, scan for signals of positive selection, and perform targeted genetic association with measured height variation. We identify multiple regions throughout the genome that may have played a role in adaptive evolution, many of which contain loci with roles in growth hormone, insulin, and insulin-like growth factor signaling pathways, as well as immunity and neuroendocrine signaling involved in reproduction and metabolism. The most striking results are found on chromosome 3, which harbors a cluster of selection and association signals between approximately 45 and 60 Mb. This region also includes the positional candidate genes DOCK3, which is known to be associated with height variation in Europeans, and CISH, a negative regulator of cytokine signaling known to inhibit growth hormone-stimulated STAT5 signaling. Finally, pathway analysis for genes near the strongest signals of association with height indicates enrichment for loci involved in insulin and insulin-like growth factor signaling

A multidisciplinary consensus on the morphological and functional responses to immunotherapy treatment

The implementation of immunotherapy has radically changed the treatment of oncological patients. Currently, immunotherapy is indicated in the treatment of patients with head and neck tumors, melanoma, lung cancer, bladder tumors, colon cancer, cervical cancer, breast cancer, Merkel cell carcinoma, liver cancer, leukemia and lymphomas. However, its efficacy is restricted to a limited number of cases. The challenge is, therefore, to identify which subset of patients would benefit from immunotherapy. To this end, the establishment of immunotherapy response criteria and predictive and prognostic biomarkers is of paramount interest. In this report, a group of experts of the Spanish Society of Medical Oncology (SEOM), the Spanish Society of Medical Radiology (SERAM), and Spanish Society of Nuclear Medicine and Molecular Imaging (SEMNIM) provide an up-to-date review and a consensus guide on these issues

An early history of T cell-mediated cytotoxicity.

After 60 years of intense fundamental research into T cell-mediated cytotoxicity, we have gained a detailed knowledge of the cells involved, specific recognition mechanisms and post-recognition perforin-granzyme-based and FAS-based molecular mechanisms. What could not be anticipated at the outset was how discovery of the mechanisms regulating the activation and function of cytotoxic T cells would lead to new developments in cancer immunotherapy. Given the profound recent interest in therapeutic manipulation of cytotoxic T cell responses, it is an opportune time to look back on the early history of the field. This Timeline describes how the early findings occurred and eventually led to current therapeutic applications