Where teachers are few: documenting available faculty in five Tanzanian medical schools.

BACKGROUND:Faced with one of the lowest physician-to-population ratios in the world, the Government of Tanzania is urging its medical schools to train more physicians. The annual number of medical students admitted across the country rose from 55 in the 1990s to 1,680 approved places for the 2015/16 academic year. These escalating numbers strain existing faculty. OBJECTIVE:To describe the availability of faculty in medical schools in Tanzania. DESIGN:We identified faculty lists published on the Internet by five Tanzanian medical schools for the 2011/12 academic year and analyzed the appointment status, rank, discipline, and qualifications of faculty members. RESULTS:The five schools reported 366 appointed faculty members (excluding visiting, part-time, or honorary appointments) for an estimated total enrolled student capacity of 3,275. Thirty-eight percent of these faculty were senior lecturers or higher. Twenty-seven percent of the appointments were in basic science, 51% in clinical science, and 21% in public health departments. The most populated disciplines (more than 20 faculty members across the five institutions) were biochemistry and molecular biology, medicine, obstetrics and gynecology, pediatrics, and surgery; the least populated disciplines (less than 10 faculty members) were anesthesiology, behavioral sciences, dermatology, dental surgery, emergency medicine, hematology, ophthalmology, orthopedics, otorhinolaryngology, oncology and radiology, psychiatry. These figures are only indicative of faculty numbers because of differences in the way the schools published their faculty lists. CONCLUSIONS:Universities are not recruiting faculty at the same rate that they are admitting students, and there is an imbalance in the distribution of faculty across disciplines. Although there are differences among the universities, all are struggling to recruit and retain staff. If Tanzanian universities, the government, donors, and international partners commit resources to develop, recruit, and retain new faculty, Tanzania could build faculty numbers to permit a quality educational experience for its doctors of tomorrow

Chk1 Haploinsufficiency Results in Anemia and Defective Erythropoiesis

Erythropoiesis is a highly regulated and well-characterized developmental process responsible for providing the oxygen transport system of the body. However, few of the mechanisms involved in this process have been elucidated. Checkpoint Kinase 1 (Chk1) is best known for its role in the cell cycle and DNA damage pathways, and it has been shown to play a part in several pathways which when disrupted can lead to anemia.Here, we show that haploinsufficiency of Chk1 results in 30% of mice developing anemia within the first year of life. The anemic Chk1+/- mice exhibit distorted spleen and bone marrow architecture, and abnormal erythroid progenitors. Furthermore, Chk1+/- erythroid progenitors exhibit an increase in spontaneous DNA damage foci and improper contractile actin ring formation resulting in aberrant enucleation during erythropoiesis. A decrease in Chk1 RNA has also been observed in patients with refractory anemia with excess blasts, further supporting a role for Chk1 in clinical anemia.Clinical trials of Chk1 inhibitors are currently underway to treat cancer, and thus it will be important to track the effects of these drugs on red blood cell development over an extended period. Our results support a role for Chk1 in maintaining the balance between erythroid progenitors and enucleated erythroid cells during differentiation. We show disruptions in Chk1 levels can lead to anemia

Reversible binding of platelet-derived growth factor-AA, -AB, and -BB isoforms to a similar site on the "slow" and "fast" conformations of alpha 2-macroglobulin.

The mechanism by which the platelet-derived growth factor (PDGF)-binding protein, alpha 2-macroglobulin (alpha 2M), modulates PDGF bioactivity is unknown, but could involve reversible PDGF-alpha 2M binding. Herein we report that greater than 70% of 125I-PDGF-BB or -AB complexed to alpha 2M was dissociated by SDS-denaturation followed by SDS-polyacrylamide gel electrophoresis, i.e. most of the binding was noncovalent. Reduction of the PDGF.alpha 2M complex following denaturation dissociated the cytokine from alpha 2M by greater than 90%, suggesting covalent disulfide bond formation. Approximately 50% of the growth factor was dissociated by lowering the pH from 7.5 to 4.0. 125I-PDGF-BB bound alpha 2M in a time-dependent manner (t1/2 = approximately 1 h), reaching equilibrium after 4 h. The 125I-PDGF.BB/alpha 2M complex dissociated more slowly (t1/2 = approximately 2.5 h). "Slow" and "fast" alpha 2M bound nearly equal amounts of PDGF-AB or -BB. Trypsin treatment converted PDGF-BB/alpha 2M complex to the fast conformation but did not release bound 125I-PDGF-BB. All PDGF-isoforms (AA, -AB, and -BB) competed for binding with 125I-PDGF-BB binding to slow alpha 2M and fast alpha 2M-methylamine by 65-80%. Other cytokines that bind alpha 2M (transforming growth factor-beta 1 and -beta 2, tumor necrosis factor-alpha, basic fibroblast growth factor, interleukin -1 beta, and -6) did not compete for 125I-PDGF-BB binding slow alpha 2M, but transforming growth factor-beta 1 and basic fibroblast growth factor inhibited 125I-PDGF-BB binding alpha 2M-methylamine by 30-50%. The reversible nature of the PDGF.alpha 2M complex could allow for targeted PDGF release near mesenchymal cells which possess PDGF receptors

Enhancement of perfluoropolyether boundary lubrication performance: I. Preliminary results

A ball bearing simulator operating under starved conditions was used to evaluate the boundary lubrication performance of a perfluoropolyether (PFPE) Krytox 143 AB. Several approaches to enhance boundary lubrication were studied. These included: (1) soluble boundary additives, (2) bearing surface modifications, (3) 'run-in' surface films, and (4) ceramic bearing components. In addition, results were compared with two non-perfluorinated liquid lubricant formulations. Based on these preliminary tests, the following tentative conclusions can be made: (1) substantial improvements in boundary lubrication performance were observed with a beta-diketone boundary additive and a tricresyl phosphate (TCP) liquid surface pretreatment; (2) the use of rough Si3N4 balls (Ra = 40 micro-in) also provided substantial improvement but with concomitant abrasive wear; (3) marginal improvements were seen with two boundary additives (a phosphine and a phosphatriazine) and a neat (100%) fluid (a carboxylic acid terminated PFPE); and surface pretreatments with a synthetic hydrocarbon, a PTFE coating, and TiC coated 440C and smooth Si3N4 balls (R(sub a) less than 1 micro-in); and (4) two non-PFPE lubricant formulations (a PAO and a synthetic hydrocarbon) yielded substantial improvements

A bibliometric review of financial market integration literature

We undertake a meta-literature review on the topic of financial market integration (FMI), covering 260 articles from 1981 to 2021. Our review consists of quantitative analysis of bibliometric citations concomitant with qualitative analysis of content, towards a goal of identifying primary research streams and proposing directions for future research. We identify five research groups: (1) portfolio diversification with financial market integration; (2) general equity market integration; (3) financial market linkage with respect to crises and events; (4) time-varying financial market integration; and (5) co-movements and spillovers between commodities and financial markets; as well as present a wide array of future research directions. We conduct an extensive review of FMI literature, answering several questions: (1) What is the domain of FMI research?; (2) What are the influential aspects of top journals and authors, and the characteristics of the most studied topics?; (3) What are the past and current key research streams in FMI literature?; and (4) What are the substantial future relevant research questions to explore regarding FMI? Given the ongoing attention on financial market integration by both academicians and policy makers, our results should be of great interest

Clinical actionability of comprehensive genomic profiling for management of rare or refractory cancers

Background. The frequency with which targeted tumor sequencing results will lead to implemented change in care is unclear. Prospective assessment of the feasibility and limitations of using genomic sequencing is critically important. Methods. A prospective clinical study was conducted on 100 patients with diverse-histology, rare, or poor-prognosis cancers to evaluate the clinical actionability of a Clinical Laboratory Improvement Amendments (CLIA)-certified, comprehensive genomic profiling assay (FoundationOne), using formalin-fixed, paraffin-embedded tumors. The primary objectives were to assess utility, feasibility, and limitations of genomic sequencing for genomically guided therapy or other clinical purpose in the setting of a multidisciplinary molecular tumor board. Results. Of the tumors from the 92 patients with sufficient tissue, 88 (96%) had at least one genomic alteration (average 3.6, range 0–10). Commonly altered pathways included p53 (46%), RAS/RAF/MAPK (rat sarcoma; rapidly accelerated fibrosarcoma; mitogen-activated protein kinase) (45%), receptor tyrosine kinases/ligand (44%), PI3K/AKT/mTOR (phosphatidylinositol-4,5-bisphosphate 3-kinase; protein kinase B; mammalian target of rapamycin) (35%), transcription factors/regulators (31%), and cell cycle regulators (30%). Many low frequency but potentially actionable alterations were identified in diverse histologies. Use of comprehensive profiling led to implementable clinical action in 35% of tumors with genomic alterations, including genomically guided therapy, diagnostic modification, and trigger for germline genetic testing. Conclusion. Use of targeted next-generation sequencing in the setting of an institutional molecular tumor board led to implementable clinical action in more than one third of patients with rare and poor-prognosis cancers. Major barriers to implementation of genomically guided therapy were clinical status of the patient and drug access. Early and serial sequencing in the clinical course and expanded access to genomically guided early-phase clinical trials and targeted agents may increase actionability. Implications for Practice: Identification of key factors that facilitate use of genomic tumor testing results and implementation of genomically guided therapy may lead to enhanced benefit for patients with rare or difficult to treat cancers. Clinical use of a targeted next-generation sequencing assay in the setting of an institutional molecular tumor board led to implementable clinical action in over one third of patients with rare and poor prognosis cancers. The major barriers to implementation of genomically guided therapy were clinical status of the patient and drug access both on trial and off label. Approaches to increase actionability include early and serial sequencing in the clinical course and expanded access to genomically guided early phase clinical trials and targeted agents

A link between the ice nucleation activity and the biogeochemistry of seawater

Emissions of ice-nucleating particles (INPs) from sea spray can impact climate and precipitation by changing cloud formation, precipitation, and albedo. However, the relationship between seawater biogeochemistry and the ice nucleation activity of sea spray aerosols remains unclarified. Here, we demonstrate a link between the biological productivity in seawater and the ice nucleation activity of sea spray aerosol under conditions relevant to cirrus and mixed-phase cloud formation. We show for the first time that aerosol particles generated from both subsurface and microlayer seawater from the highly productive eastern tropical North Pacific Ocean are effective INPs in the deposition and immersion freezing modes. Seawater particles of composition similar to subsurface waters of highly productive regions may therefore be an unrealized source of effective INPs. In contrast, the subsurface water from the less productive Florida Straits produced less effective immersion mode INPs and ineffective depositional mode INPs. These results indicate that the regional biogeochemistry of seawater can strongly affect the ice nucleation activity of sea spray aerosol

Roadmap to a Comprehensive Clinical Data Warehouse for Precision Medicine Applications in Oncology

Leading institutions throughout the country have established Precision Medicine programs to support personalized treatment of patients. A cornerstone for these programs is the establishment of enterprise-wide Clinical Data Warehouses. Working shoulder-to-shoulder, a team of physicians, systems biologists, engineers, and scientists at Rutgers Cancer Institute of New Jersey have designed, developed, and implemented the Warehouse with information originating from data sources, including Electronic Medical Records, Clinical Trial Management Systems, Tumor Registries, Biospecimen Repositories, Radiology and Pathology archives, and Next Generation Sequencing services. Innovative solutions were implemented to detect and extract unstructured clinical information that was embedded in paper/text documents, including synoptic pathology reports. Supporting important precision medicine use cases, the growing Warehouse enables physicians to systematically mine and review the molecular, genomic, image-based, and correlated clinical information of patient tumors individually or as part of large cohorts to identify changes and patterns that may influence treatment decisions and potential outcomes