Probing Dark Matter

Recent novel observations have probed the baryonic fraction of the galactic dark matter that has eluded astronomers for decades. Late in 1993, the MACHO and EROS collaborations announced in this journal the detection of transient and achromatic brightenings of a handful of stars in the Large Magellanic Cloud that are best interpreted as gravitational microlensing by low-mass foreground objects (MACHOS). This tantalized astronomers, for it implied that the population of cool, compact objects these lenses represent could be the elusive dark matter of our galactic halo. A year later in 1994, Sackett et al. reported the discovery of a red halo in the galaxy NGC 5907 that seems to follow the inferred radial distribution of its dark matter. This suggested that dwarf stars could constitute its missing component. Since NGC 5907 is similar to the Milky Way in type and radius, some surmised that the solution of the galactic dark matter problem was an abundance of ordinary low-mass stars. Now Bahcall et al., using the Wide-Field Camera of the recently repaired Hubble Space Telescope, have dashed this hope.Comment: 3 pages, Plain TeX, no figures, published as a News and Views in Nature 373, 191 (1995

Measurement of Indoor and Outdoor Background Ionising Radiation Levels of Kwali General Hospital, Abuja

Measurement of indoor and outdoor background ionising radiation level at Kwali General Hospital, Abuja, Nigeria was carried out using a well calibrated Geiger muller counter; Atomtex AT1117M radiation monitor. The dose equivalent results obtained range from 0.100±0.001 ìSv/h to 0.124±0.007 µSv/h with an average of 0.107±0.003 ìSv/h for indoor measurement while it ranges from 0.100±0.001 µSv/h to 0.122±0.003 µSv/h with an average of0.108±0.003 µSv/h for outdoor measurement respectively. The obtained values are below the standard background radiation of 0.133 µSv/h. The study also revealed that the average annual equivalent dose rate is 0.750± 0.020 mSv/y and 0.189±0.005 mSv/y for indoor and outdoor measurements respectively. These results revealed that the dose levels in all of the locations (indoor and outdoor) were below the 1 mSv/y maximum permissible limit for the public set by International Commission on Radiological Protection (ICRP). Therefore, Kwali General Hospital is radiologically safe ©JASE

Defining the roles of Data Manager and Epidemiologist in emergency medical teams

Funding: Hong Kong Jockey Club Charity Trust within the collaborative project “Training and Research Development for Emergency Medical Teams with reference to the WHO Global EMTs initiative, classification, and standards” between the Humanitarian and Conflict Response Institute (HCRI; Manchester, United Kingdom) and the Hong Kong Jockey Club Disaster Preparedness and Response Institute (HKJCDPRI; Aberdeen, Hong Kong).Medical and epidemiological documentation in disasters is pivotal: the former for recording patient care and the latter for providing real-time information to the host country. Furthermore, documentation informs post-hoc analysis to improve the effectiveness of future deployments. Although documentation is considered important and indeed integral to health care response, there are many barriers and challenges. Some of these challenges include: working without well-established standards for medical documentation; and working with international guidelines which provide minimal guidance as to how health data should be managed practically to ensure accuracy and completion. Furthermore, there is a shift in mindset in disaster contexts wherein most health care focus shifts to direct clinical care and diverts almost all attention from quality documentation. This report distinguishes between the tasks of the epidemiologist and the data manager (DM) in an emergency medical team (EMT) and discusses the importance of data collection in the specific case of an EMT deployment. While combining these roles is sometimes possible if resources are limited, it is better to separate them, as the two are quite distinct. Although there is overlap, to achieve the goals of either role, preferentially they should be carried out by two people working closely together with complementary skill sets. The main objective of this report is to provide guidance and task descriptions to EMTs and field hospitals when training, recruiting, and preparing DMs and epidemiologists to work within their teams. Clear delineation of tasks will lead to better quality data, as it commits DMs to being concerned with the provision of real-time documentation from patient arrival through to compiling daily reports. It also commits epidemiologists to providing enhanced disease surveillance; outbreak investigation; and a source of reliable and actionable information for decision makers and stakeholders in the disaster management cycle.PostprintPeer reviewe

Delayed onset of changes in soma action potential genesis in nociceptive A-beta DRG neurons in vivo in a rat model of osteoarthritis

<p>Abstract</p> <p>Background</p> <p>Clinical data on osteoarthritis (OA) suggest widespread changes in sensory function that vary during the progression of OA. In previous studies on a surgically-induced animal model of OA we have observed that changes in structure and gene expression follow a variable trajectory over the initial days and weeks. To investigate mechanisms underlying changes in sensory function in this model, the present electrophysiological study compared properties of primary sensory nociceptive neurons at one and two months after model induction with properties in naïve control animals. Pilot data indicated no difference in C- or Aδ-fiber associated neurons and therefore the focus is on Aβ-fiber nociceptive neurons.</p> <p>Results</p> <p>At one month after unilateral derangement of the knee by cutting the anterior cruciate ligament and removing the medial meniscus, the only changes observed in Aβ-fiber dorsal root ganglion (DRG) neurons were in nociceptor-like unresponsive neurons bearing a hump on the repolarization phase; these changes consisted of longer half width, reflecting slowed dynamics of AP genesis, a depolarized Vm and an increased AP amplitude. At two months, changes observed were in Aβ-fiber high threshold mechanoreceptors, which exhibited shorter AP duration at base and half width, shorter rise time and fall time, and faster maximum rising rate/maximum falling rate, reflecting accelerated dynamics of AP genesis.</p> <p>Conclusion</p> <p>These data indicate that Aβ nociceptive neurons undergo significant changes that vary in time and occur later than changes in structure and in nociceptive scores in this surgically induced OA model. Thus, if changes in Aβ-fiber nociceptive neurons in this model reflect a role in OA pain, they may relate to mechanisms underlying pain associated with advanced OA.</p

An Integrated Imaging Approach to the Study of Oxidative Stress Generation by Mitochondrial Dysfunction in Living Cells

BACKGROUND: The mechanisms of action of many environmental agents commonly involve oxidative stress resulting from mitochondrial dysfunction. Zinc is a common environmental metallic contaminant that has been implicated in a variety of oxidant-dependent toxicological responses. Unlike ions of other transition metals such as iron, copper, and vanadium, Zn(2+) does not generate reactive oxygen species (ROS) through redox cycling. OBJECTIVE: To characterize the role of oxidative stress in zinc-induced toxicity. METHODS: We used an integrated imaging approach that employs the hydrogen peroxide (H2O2)-specific fluorophore Peroxy Green 1 (PG1), the mitochondrial potential sensor 5,5 ,6,6 -tetrachloro-1,1 ,3,3 -tetraethylbenzimidazolylcarbocyanine iodide (JC-1), and the mitochondria-targeted form of the redox-sensitive genetically encoded fluorophore MTroGFP1 in living cells. RESULTS: Zinc treatment in the presence of the Zn(2+) ionophore pyrithione of A431 skin carcinoma cells preloaded with the H(2)O(2)-specific indicator PG1 resulted in a significant increase in H(2)O(2) production that could be significantly inhibited with the mitochondrial inhibitor carbonyl cyanide 3-chlorophenylhydrazone. Mitochondria were further implicated as the source of zinc-induced H(2)O(2) formation by the observation that exposure to zinc caused a loss of mitochondrial membrane potential. Using MTroGFP1, we showed that zinc exposure of A431 cells induces a rapid loss of reducing redox potential in mitochondria. We also demonstrated that zinc exposure results in rapid swelling of mitochondria isolated from mouse hearts. CONCLUSION: Taken together, these findings show a disruption of mitochondrial integrity, H(2)O(2) formation, and a shift toward positive redox potential in cells exposed to zinc. These data demonstrate the utility of real-time, live-cell imaging to study the role of oxidative stress in toxicological responses

New directions in cellular therapy of cancer: a summary of the summit on cellular therapy for cancer

A summit on cellular therapy for cancer discussed and presented advances related to the use of adoptive cellular therapy for melanoma and other cancers. The summit revealed that this field is advancing rapidly. Conventional cellular therapies, such as tumor infiltrating lymphocytes (TIL), are becoming more effective and more available. Gene therapy is becoming an important tool in adoptive cell therapy. Lymphocytes are being engineered to express high affinity T cell receptors (TCRs), chimeric antibody-T cell receptors (CARs) and cytokines. T cell subsets with more naïve and stem cell-like characteristics have been shown in pre-clinical models to be more effective than unselected populations and it is now possible to reprogram T cells and to produce T cells with stem cell characteristics. In the future, combinations of adoptive transfer of T cells and specific vaccination against the cognate antigen can be envisaged to further enhance the effectiveness of these therapies

Estrogen as therapy for breast cancer

High-dose estrogen was generally considered the endocrine therapy of choice for postmenopausal women with breast cancer prior to the introduction of tamoxifen. Subsequently, the use of estrogen was largely abandoned. Recent clinical trial data have shown clinically meaningful efficacy for high-dose estrogen even in patients with extensive prior endocrine therapy. Preclinical research has demonstrated that the estrogen dose-response curve for breast cancer cells can be shifted by modification of the estrogen environment. Clinical and laboratory data together provide the basis for developing testable hypotheses of management strategies, with the potential of increasing the value of endocrine therapy in women with breast cancer