Speech Communication

Contains research objectives and summary of research on six research projects and reports on three research projects.National Institutes of Health (Grant 5 RO1 NS04332-13)National Institutes of Health (Fellowship 1 F22 MH5825-01)National Institutes of Health (Grant 1 T32 NS07040-01)National Institutes of Health (Fellowship 1 F22 NS007960)National Institutes of Health (Fellowship 1 F22 HD019120)National Institutes of Health (Fellowship 1 F22 HD01919-01)U. S. Army (Contract DAAB03-75-C-0489)National Institutes of Health (Grant 5 RO1 NS04332-12

Reproductive aspects of the oceanic whitetip shark, Carcharhinus longimanus (Elasmobranchii: Carcharhinidae), in the equatorial and southwestern Atlantic Ocean

The present study sought to study the reproductive biology of the oceanic whitetip shark, Carcharhinus longimanus, in the equatorial and southwestern Atlantic Ocean. A total of 234 specimens were collected as bycatch during pelagic longline fisheries targeting tunas and swordfish, between December 2003 and December 2010. The fishing area was located between latitudes 10N and 35S and longitudes 3E and 40W. Of the 234 individuals sampled, 118 were females (with sizes ranging from 81 to 227 cm TL, total length) and 116 males (ranging from 80 to 242 cm TL). The reproductive stages of the females were classed as immature, mature, preovulatory and pregnant, while males were divided into immature, maturing and mature. The size at maturity for females was estimated at 170.0 cm TL, while that for males was between 170.0 and 190.0 cm TL. Ovarian fecundity ranged from 1 to 10 follicles and uterine fecundity from 1 to 10 embryos. The reproductive cycle of this species is most likely biennial, with parturition occurring once every two years.info:eu-repo/semantics/publishedVersio

Toward New Therapeutics for Skin and Soft Tissue Infections: Propargyl-Linked Antifolates Are Potent Inhibitors of MRSA and Streptococcus pyogenes

Hospital- and community-acquired, complicated skin and soft tissue infections, often attributed to Staphylococcus aureus and Streptococcus pyogenes, present a significant health burden that is associated with increased health care costs and mortality. As these two species are difficult to discern on diagnosis and are associated with differential profiles of drug resistance, the development of an efficacious antibacterial agent that targets both organisms is a high priority. Herein we describe a structure-based drug development effort that has produced highly potent inhibitors of dihydrofolate reductase from both species. Optimized propargyl-linked antifolates containing a key pyridyl substituent display antibacterial activity against both methicillin-resistant S. aureus and S. pyogenes at MIC values below 0.1 µg/mL and minimal cytotoxicity against mammalian cells. Further evaluation against a panel of clinical isolates shows good efficacy against a range of important phenotypes such as hospital- and community-acquired strains as well as strains resistant to vancomycin

Effectiveness of computer-navigated minimally invasive total hip surgery compared to conventional total hip arthroplasty: design of a randomized controlled trial

BACKGROUND: Moderate to severe osteoarthrosis is the most common indication for Total Hip Arthroplasty (THA). Minimally Invasive Total Hip Surgery (MIS) and computer-navigated surgery were introduced several years ago. However, the literature lacks well-designed studies that provide evidence of superiority of computer-navigated MIS over a conventional THA technique. Hence, the purpose of this study is to compare (cost)effectiveness of computer-navigated MIS with a conventional technique for THA. It is our hypothesis that computer-navigated MIS will lead to a quicker recovery during the early postoperative period (3 months), and to an outcome at least as good 6 months postoperatively. We also hypothesize that computer-navigated MIS leads to fewer perioperative complications and better prosthesis positioning. Furthermore, cost advantages of computer-navigated MIS over conventional THA technique are expected. METHODS/DESIGN: A cluster randomized controlled trial will be executed. Patients between the ages of 18 and 75 admitted for primary cementless unilateral THA will be included. Patients will be stratified using the Charnley classification. They will be randomly allocated to have computer-navigated MIS or conventional THA technique. Measurements take place preoperatively, perioperatively, and 6 weeks and 3 and 6 months postoperatively. Degree of limping (gait analysis), self-reported functional status and health-related quality of life (questionnaires) will be assessed preoperatively as well as postoperatively. Perioperative complications will be registered. Radiographic evaluation of prosthesis positioning will take place 6 weeks postoperatively. An evaluation of costs within and outside the healthcare sector will focus on differences in costs between computer-navigated MIS and conventional THA technique. DISCUSSION: Based on studies performed so far, few objective data quantifying the risks and benefits of computer-navigated MIS are available. Therefore, this study has been designed to compare (cost) effectiveness of computer-navigated MIS with a conventional technique for THA. The results of this trial will be presented as soon as they become available

Can COBE see the shape of the universe?

In recent years, the large angle COBE--DMR data have been used to place constraints on the size and shape of certain topologically compact models of the universe. Here we show that this approach does not work for generic compact models. In particular, we show that compact hyperbolic models do not suffer the same loss of large angle power seen in flat or spherical models. This follows from applying a topological theorem to show that generic hyperbolic three manifolds support long wavelength fluctuations, and by taking into account the dominant role played by the integrated Sachs-Wolfe effect in a hyperbolic universe.Comment: 16 Pages, 5 Figures. Version published in Phys. Rev.

Minimally invasive and computer-navigated total hip arthroplasty: a qualitative and systematic review of the literature

ABSTRACT: BACKGROUND: Both minimally invasive surgery (MIS) and computer-assisted surgery (CAS) for total hip arthroplasty (THA) have gained popularity in recent years. We conducted a qualitative and systematic review to assess the effectiveness of MIS, CAS and computer-assisted MIS for THA. METHODS: An extensive computerised literature search of PubMed, Medline, Embase and OVIDSP was conducted. Both randomised clinical trials and controlled clinical trials on the effectiveness of MIS, CAS and computer-assisted MIS for THA were included. Methodological quality was independently assessed by two reviewers. Effect estimates were calculated and a best-evidence synthesis was performed. RESULTS: Four high-quality and 14 medium-quality studies with MIS THA as study contrast, and three high-quality and four medium-quality studies with CAS THA as study contrast were included. No studies with computer-assisted MIS for THA as study contrast were identified. Strong evidence was found for a decrease in operative time and intraoperative blood loss for MIS THA, with no difference in complication rates and risk for acetabular outliers. Strong evidence exists that there is no difference in physical functioning, measured either by questionnaires or by gait analysis. Moderate evidence was found for a shorter length of hospital stay after MIS THA. Conflicting evidence was found for a positive effect of MIS THA on pain in the early postoperative period, but that effect diminished after three months postoperatively. Strong evidence was found for an increase in operative time for CAS THA, and limited evidence was found for a decrease in intraoperative blood loss. Furthermore, strong evidence was found for no difference in complication rates, as well as for a significantly lower risk for acetabular outliers. CONCLUSIONS: The results indicate that MIS THA is a safe surgical procedure, without increases in operative time, blood loss, operative complication rates and component malposition rates. However, the beneficial effect of MIS THA on functional recovery has to be proven. The results also indicate that CAS THA, though resulting in an increase in operative time, may have a positive effect on operative blood loss and operative complication rates. More importantly, the use of CAS results in better positioning of acetabular component of the prosthesis

Dynamic purine signaling and metabolism during neutrophil–endothelial interactions

During episodes of hypoxia and inflammation, polymorphonuclear leukocytes (PMN) move into underlying tissues by initially passing between endothelial cells that line the inner surface of blood vessels (transendothelial migration, TEM). TEM creates the potential for disturbances in vascular barrier and concomitant loss of extravascular fluid and resultant edema. Recent studies have demonstrated a crucial role for nucleotide metabolism and nucleoside signaling during inflammation. These studies have implicated multiple adenine nucleotides as endogenous tissue protective mechanisms invivo. Here, we review the functional components of vascular barrier, identify strategies for increasing nucleotide generation and nucleoside signaling, and discuss potential therapeutic targets to regulate the vascular barrier during inflammation

Planck 2015 results. XVIII. Background geometry and topology of the Universe

Maps of cosmic microwave background (CMB) temperature and polarization from the 2015 release of Planck data provide the highestquality full-sky view of the surface of last scattering available to date. This enables us to detect possible departures from a globally isotropic cosmology. We present the first searches using CMB polarization for correlations induced by a possible non-trivial topology with a fundamental domain that intersects, or nearly intersects, the last-scattering surface (at comoving distance χrec), both via a direct scan for matched circular patterns at the intersections and by an optimal likelihood calculation for specific topologies. We specialize to flat spaces with cubic toroidal (T3) and slab (T1) topologies, finding that explicit searches for the latter are sensitive to other topologies with antipodal symmetry. These searches yield no detection of a compact topology with a scale below the diameter of the last-scattering surface. The limits on the radius ℛi of the largest sphere inscribed in the fundamental domain (at log-likelihood ratio Δlnℒ > −5 relative to a simply-connected flat Planck best-fit model) are: ℛi > 0.97 χrec for the T3 cubic torus; and ℛi > 0.56 χrec for the T1 slab. The limit for the T3 cubic torus from the matched-circles search is numerically equivalent, ℛi > 0.97 χrec at 99% confidence level from polarization data alone. We also perform a Bayesian search for an anisotropic global Bianchi VIIh geometry. In the non-physical setting, where the Bianchi cosmology is decoupled from the standard cosmology, Planck temperature data favour the inclusion of a Bianchi component with a Bayes factor of at least 2.3 units of log-evidence. However, the cosmological parameters that generate this pattern are in strong disagreement with those found from CMB anisotropy data alone. Fitting the induced polarization pattern for this model to the Planck data requires an amplitude of −0.10 ± 0.04 compared to the value of + 1 if the model were to be correct. In the physically motivated setting, where the Bianchi parameters are coupled and fitted simultaneously with the standard cosmological parameters, we find no evidence for a Bianchi VIIh cosmology and constrain the vorticity of such models to (ω/H)0 < 7.6 × 10-10 (95% CL)

Guidelines for the use and interpretation of assays for monitoring autophagy (3rd edition)

In 2008 we published the first set of guidelines for standardizing research in autophagy. Since then, research on this topic has continued to accelerate, and many new scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Accordingly, it is important to update these guidelines for monitoring autophagy in different organisms. Various reviews have described the range of assays that have been used for this purpose. Nevertheless, there continues to be confusion regarding acceptable methods to measure autophagy, especially in multicellular eukaryotes. For example, a key point that needs to be emphasized is that there is a difference between measurements that monitor the numbers or volume of autophagic elements (e.g., autophagosomes or autolysosomes) at any stage of the autophagic process versus those that measure fl ux through the autophagy pathway (i.e., the complete process including the amount and rate of cargo sequestered and degraded). In particular, a block in macroautophagy that results in autophagosome accumulation must be differentiated from stimuli that increase autophagic activity, defi ned as increased autophagy induction coupled with increased delivery to, and degradation within, lysosomes (inmost higher eukaryotes and some protists such as Dictyostelium ) or the vacuole (in plants and fungi). In other words, it is especially important that investigators new to the fi eld understand that the appearance of more autophagosomes does not necessarily equate with more autophagy. In fact, in many cases, autophagosomes accumulate because of a block in trafficking to lysosomes without a concomitant change in autophagosome biogenesis, whereas an increase in autolysosomes may reflect a reduction in degradative activity. It is worth emphasizing here that lysosomal digestion is a stage of autophagy and evaluating its competence is a crucial part of the evaluation of autophagic flux, or complete autophagy. Here, we present a set of guidelines for the selection and interpretation of methods for use by investigators who aim to examine macroautophagy and related processes, as well as for reviewers who need to provide realistic and reasonable critiques of papers that are focused on these processes. These guidelines are not meant to be a formulaic set of rules, because the appropriate assays depend in part on the question being asked and the system being used. In addition, we emphasize that no individual assay is guaranteed to be the most appropriate one in every situation, and we strongly recommend the use of multiple assays to monitor autophagy. Along these lines, because of the potential for pleiotropic effects due to blocking autophagy through genetic manipulation it is imperative to delete or knock down more than one autophagy-related gene. In addition, some individual Atg proteins, or groups of proteins, are involved in other cellular pathways so not all Atg proteins can be used as a specific marker for an autophagic process. In these guidelines, we consider these various methods of assessing autophagy and what information can, or cannot, be obtained from them. Finally, by discussing the merits and limits of particular autophagy assays, we hope to encourage technical innovation in the field