Implementing Eccentric Resistance Training—Part 1: A Brief Review of Existing Methods

The purpose of this review was to provide a physiological rationale for the use of eccentric resistance training and to provide an overview of the most commonly prescribed eccentric training methods. Based on the existing literature, there is a strong physiological rationale for the incorporation of eccentric training into a training program for an individual seeking to maximize muscle size, strength, and power. Specific adaptations may include an increase in muscle cross-sectional area, force output, and fiber shortening velocities, all of which have the potential to benefit power production characteristics. Tempo eccentric training, flywheel inertial training, accentuated eccentric loading, and plyometric training are commonly implemented in applied contexts. These methods tend to involve different force absorption characteristics and thus, overload the muscle or musculotendinous unit in different ways during lengthening actions. For this reason, they may produce different magnitudes of improvement in hypertrophy, strength, and power. The constraints to which they are implemented can have a marked effect on the characteristics of force absorption and therefore, could affect the nature of the adaptive response. However, the versatility of the constraints when prescribing these methods mean that they can be effectively implemented to induce these adaptations within a variety of populations

Working practices and incomes of health workers : evidence from an evaluation of a delivery fee exemption scheme in Ghana

Background: This article describes a survey of health workers and traditional birth attendants (TBAs) which was carried out in 2005 in two regions of Ghana. The objective of the survey was to ascertain the impact of the introduction of a delivery fee exemption scheme on both health workers and those providers who were excluded from the scheme (TBAs). This formed part of an overall evaluation of the delivery fee exemption scheme. The results shed light not only on the scheme itself but also on the general productivity of a range of health workers in Ghana. Methods: A structured questionnaire was developed, covering individual and household characteristics, working hours and practices, sources of income, and views of the exemptions scheme and general motivation. After field testing, this was administered to 374 respondents in 12 districts of Central and Volta regions. The respondents included doctors, medical assistants (MAs), public and private midwives, nurses, community health nurses (CHNs), and traditional birth attendants, both trained and untrained. Results: Health workers were well informed about the delivery fee exemptions scheme and their responses on its impact suggest a realistic view that it was a good scheme, but one that faces serious challenges regarding financial sustainability. Concerning its impact on their morale and working conditions, the responses were broadly neutral. Most public sector workers have seen an increased workload, but counterbalanced by increased pay. TBAs have suffered, in terms of client numbers and income, while the picture for private midwives is mixed. The survey also sheds light on pay and productivity. The respondents report long working hours, with a mean of 54 hours per week for community nurses and up to 129 hours per week for MAs. Weekly reported client loads in the public sector range from a mean of 86 for nurses to 269 for doctors. Over the past two years, reported working hours have been increasing, but so have pay and allowances (for doctors, allowances now make up 66% of their total pay). The lowest paid public health worker now earns almost ten times the average gross national income (GNI) per capita, while the doctors earn 38.5 times GNI per capita. This compares well with average government pay of four times GNI per capita. Comparing pay with outputs, the relatively high number of clients reported by doctors reduces their pay differential, so that the cost per client – $1.09 – is similar to a nurse's (and lower than a private midwife's). Conclusion: These findings show that a scheme which increases demand for public health services while also sustaining health worker income and morale, is workable, if well managed, even within the relatively constrained human resources environment of countries like Ghana. This may be linked to the fact that internal comparisons reveal Ghana's health workers to be well paid from public sector sources.This work was undertaken as part of an international research programme – IMMPACT (Initiative for Maternal Mortality Programme Assessment) – funded by the Bill & Melinda Gates Foundation, the Department for International Development, the European Commission and USAID

Assessing the clinical utility of cancer genomic and proteomic data across tumor types

Molecular profiling of tumors promises to advance the clinical management of cancer, but the benefits of integrating molecular data with traditional clinical variables have not been systematically studied. Here we retrospectively predict patient survival using diverse molecular data (somatic copy-number alteration, DNA methylation and mRNA, miRNA and protein expression) from 953 samples of four cancer types from The Cancer Genome Atlas project. We found that incorporating molecular data with clinical variables yielded statistically significantly improved predictions (FDR < 0.05) for three cancers but those quantitative gains were limited (2.2–23.9%). Additional analyses revealed little predictive power across tumor types except for one case. In clinically relevant genes, we identified 10,281 somatic alterations across 12 cancer types in 2,928 of 3,277 patients (89.4%), many of which would not be revealed in single-tumor analyses. Our study provides a starting point and resources, including an open-access model evaluation platform, for building reliable prognostic and therapeutic strategies that incorporate molecular data

Effects of B vitamins on protein utilization from rice-legume dietaries by the growing rat

This article does not have an abstract

Construction and Validation of Nepali Teachers’ Self-Efficacy and Classroom Management Practices Instruments Through the E-Delphi Technique

This study presents the processes applied in developing and validating Nepali Classroom Management Practices (CMPS) and Nepali Teachers’ Self-Efficacy (NTSE) instruments. The instruments were developed using the e-Delphi technique. To find the consensus benchmark of the responses, the study used a five-point Likert scale and used Microsoft Excel to analyze responses. The items that achieved a 75% consensus were accepted. Following the interviews and two rounds of questionnaire administration, 28 items from the initial 35 for NTSE and 24 items from the initial 52 for CMP were found to have a high consensus among the experts. Therefore, 28-items NTSE and 24-items CMP instruments were developed to measure Nepali public school teachers’ self-efficacy and their classroom management practices. The pilot study results demonstrated that there was strong internal consistency of items with the value of the overall Cronbach’s alpha in both scales α= .86 (NTSE α = .77 and CMP α = .83). These scales can be used for educational research projects in Nepal and then be contextualized to use in other countries

Idelalisib sensitivity and mechanisms of disease progression in relapsed TCF3-PBX1 acute lymphoblastic leukemia

Peer reviewe

Activating mTOR Mutations in a Patient with an Extraordinary Response on a Phase I Trial of Everolimus and Pazopanib

Understanding the genetic mechanisms of sensitivity to targeted anticancer therapies may improve patient selection, response to therapy, and rational treatment designs. One approach to increase this understanding involves detailed studies of exceptional responders: rare patients with unexpected exquisite sensitivity or durable responses to therapy. We identified an exceptional responder in a phase I study of pazopanib and everolimus in advanced solid tumors. Whole-exome sequencing of a patient with a 14-month complete response on this trial revealed two concurrent mutations in mTOR, the target of everolimus. In vitro experiments demonstrate that both mutations are activating, suggesting a biologic mechanism for exquisite sensitivity to everolimus in this patient. The use of precision (or “personalized”) medicine approaches to screen patients with cancer for alterations in the mTOR pathway may help to identify subsets of patients who may benefit from targeted therapies directed against mTOR.National Human Genome Research Institute (U.S.) (5U54HG003067-11

Geomorphology and surficial geology of the Western continental shelf and upper slope of India: a review

The geomorphology and geology of the western con­tinental margin of India have become better known only after the International Indian Ocean Expedition (1962-1965). The continental shelf of western India is wide off the river mouths, becoming narrower south-eastwards and narrowest on the SW margin. Shelf break occurs at depths between 60 and 150 m. The Fifty Fathom Flat is a prominent feature on the outer shelf. Submarine terraces at depths between 35 and 170 m and shelf edge reefs are also present along the margin. Coastal geology and geomorphology of the area and nearshore currents played a significant role in the distribution of placer minerals off Kerala and Maharashtra. Transport and sedimentation of fine­ grained materials at places on the shelf are influ­enced by high-energy conditions. Clay minerals de­ rived from the Indus, Deccan Trap basalt and Gneissic provinces are distinct along the inner shelf, but bypassed the outer shelf and got deposited on the continental slope. Relict biogenic carbonates com­ prising Halimeda litho-facies, rhodalgal-coral facies and molechfer facies, occur in the northern, central and southwestern shelf, respectively. Terrestrial limestones described as palaeo-shoreline indicators occur at mid-shelf. Several evidences exist in favour of Late Quaternary neotectonic activity and subsidence. Phosphorites and phosphatized limestones occur on the shelf and slope and phosphatization seems to be a short event in the Early Holocene. Verdine and Glau­cony facies occur on the shelf and slope of the central and southwestern margin of India. Systematic sampling/radiocarbon dating is lacking on many geomorphic features. Some coastal bays in Maharashtra are least explored for heavy minerals. Phosphorites at places could prove economic, if de­tailed exploration is done. Several gaps exist in the data on sea level changes during the Late Quater­nary. Shelf edge exchange processes are to be studied in understanding the organic carbon distribution. Attention should be directed in solving the problems highlighted

Colon cancer-derived oncogenic EGFR G724S mutant identified by whole genome sequence analysis is dependent on asymmetric dimerization and sensitive to cetuximab

Background: Inhibition of the activated epidermal growth factor receptor (EGFR) with either enzymatic kinase inhibitors or anti-EGFR antibodies such as cetuximab, is an effective modality of treatment for multiple human cancers. Enzymatic EGFR inhibitors are effective for lung adenocarcinomas with somatic kinase domain EGFR mutations while, paradoxically, anti-EGFR antibodies are more effective in colon and head and neck cancers where EGFR mutations occur less frequently. In colorectal cancer, anti-EGFR antibodies are routinely used as second-line therapy of KRAS wild-type tumors. However, detailed mechanisms and genomic predictors for pharmacological response to these antibodies in colon cancer remain unclear. Findings: We describe a case of colorectal adenocarcinoma, which was found to harbor a kinase domain mutation, G724S, in EGFR through whole genome sequencing. We show that G724S mutant EGFR is oncogenic and that it differs from classic lung cancer derived EGFR mutants in that it is cetuximab responsive in vitro, yet relatively insensitive to small molecule kinase inhibitors. Through biochemical and cellular pharmacologic studies, we have determined that cells harboring the colon cancer-derived G719S and G724S mutants are responsive to cetuximab therapy in vitro and found that the requirement for asymmetric dimerization of these mutant EGFR to promote cellular transformation may explain their greater inhibition by cetuximab than small-molecule kinase inhibitors. Conclusion: The colon-cancer derived G719S and G724S mutants are oncogenic and sensitive in vitro to cetuximab. These data suggest that patients with these mutations may benefit from the use of anti-EGFR antibodies as part of the first-line therapy

PIK3CA dependence and sensitivity to therapeutic targeting in urothelial carcinoma

Background Many urothelial carcinomas (UC) contain activating PIK3CA mutations. In telomerase-immortalized normal urothelial cells (TERT-NHUC), ectopic expression of mutant PIK3CA induces PI3K pathway activation, cell proliferation and cell migration. However, it is not clear whether advanced UC tumors are PIK3CA-dependent and whether PI3K pathway inhibition is a good therapeutic option in such cases. Methods We used retrovirus-mediated delivery of shRNA to knock down mutant PIK3CA in UC cell lines and assessed effects on pathway activation, cell proliferation, migration and tumorigenicity. The effect of the class I PI3K inhibitor GDC-0941 was assessed in a panel of UC cell lines with a range of known molecular alterations in the PI3K pathway. Results Specific knockdown of PIK3CA inhibited proliferation, migration, anchorage-independent growth and in vivo tumor growth of cells with PIK3CA mutations. Sensitivity to GDC-0941 was dependent on hotspot PIK3CA mutation status. Cells with rare PIK3CA mutations and co-occurring TSC1 or PTEN mutations were less sensitive. Furthermore, downstream PI3K pathway alterations in TSC1 or PTEN or co-occurring AKT1 and RAS gene mutations were associated with GDC-0941 resistance. Conclusions Mutant PIK3CA is a potent oncogenic driver in many UC cell lines and may represent a valuable therapeutic target in advanced bladder cancer