Project for the analysis of technology transfer Quarterly report, 1 Apr. 1969 - 30 Jun. 1969

Patterns, statistical analyses, and case studies of transfer and utilization of NASA generated technolog

Holographic equations of state and astrophysical compact objects

We solve the Tolman-Oppenheimer-Volkoff equation using an equation of state (EoS) calculated in holographic QCD. The aim is to use compact astrophysical objects like neutron stars as an indicator to test holographic equations of state. We first try an EoS from a dense D4/D8/\textoverline {D8} model. In this case, however, we could not find a stable compact star, a star satisfying pressure-zero condition with a radius $R$, $p(R)=0$, within a reasonable value of the radius. This means that the EoS from the D4/D8/\textoverline {D8} model may not support any stable compact stars or may support one whose radius is very large. This might be due to a deficit of attractive force from a scalar field or two-pion exchange in the D4/D8/\textoverline {D8} model. Then, we consider D4/D6 type models with different number of quark flavors, $N_f=1,2,3$. Though the mass and radius of a holographic star is larger than those of normal neutron stars, the D4/D6 type EoS renders a stable compact star.Comment: 12 pages, 9 figure

Dental Occlusion in a Split Amazon Indigenous Population: Genetics Prevails over Environment

Background: Studies examining human and nonhuman primates have supported the hypothesis that the recent increase in the occurrence of misalignment of teeth and/or incorrect relation of dental arches, named dental malocclusion, is mainly attributed to the availability of a more processed diet and the reduced need for powerful masticatory action. For the first time on live human populations, genetic and tooth wear influences on occlusal variation were examined in a split indigenous population. The Arara-Iriri people are descendants of a single couple expelled from a larger village. In the resultant village, expansion occurred through the mating of close relatives, resulting in marked genetic cohesion with substantial genetic differences. Methodology/Principal Findings: Dental malocclusion, tooth wear and inbreeding coefficient were evaluated. The sample examined was composed of 176 individuals from both villages. Prevalence Ratio and descriptive differences in the outcomes frequency for each developmental stage of the dentition were considered. Statistical differences between the villages were examined using the chi-square test or Fisher’s exact statistic. Tooth wear and the inbreeding coefficient (F) between the villages was tested with Mann-Whitney statistics. All the statistics were performed using two-tailed distribution at p#0.05. The coefficient inbreeding (F) confirmed the frequent incestuous unions among the Arara-Iriri indigenous group. Despite the tooth wear similarities, we found a striking difference in occlusal patterns between the two Arara villages. In the original village, dental malocclusion was present in about one third of the population; whilst in the resultant village, the occurrence was almost doubled. Furthermore, the morphological characteristics of malocclusion were strongly different between the groups. Conclusions/Significance: Our findings downplay the widespread influence of tooth wear, a direct evidence of what an individual ate in the past, on occlusal variation of living human populations. They also suggest that genetics plays the most important role on dental malocclusion etiology

The development and characterisation of porphyrin isothiocyanate–monoclonal antibody conjugates for photoimmunotherapy

A promising approach to increase the specificity of photosensitisers used in photodynamic therapy has been through conjugation to monoclonal antibodies (MAb) directed against tumour-associated antigens. Many of the conjugations performed to date have relied on the activated ester method, which can lead to impure conjugate preparations and antibody crosslinking. Here, we report the development of photosensitiser–MAb conjugates utilising two porphyrin isothiocyanates. The presence of a single reactive isothiocyanate allowed facile conjugation to MAb FSP 77 and 17.1A directed against internalising antigens, and MAb 35A7 that binds to a non-internalising antigen. The photosensitiser–MAb conjugates substituted with 1–3 mol of photosensitiser were characterised in vitro. No appreciable loss of immunoreactivity was observed and binding specificity was comparable to that of the unconjugated MAb. Substitution with photosensitiser had a minimal effect on antibody biodistribution in vivo for the majority of the conjugates, although a decreased serum half-life was observed using a cationic photosensitiser at the higher loading ratios. Tumour-to-normal tissue ratios as high as 33.5 were observed using MAb 35A7 conjugates. The internalising conjugate showed a higher level of phototoxicity as compared with the non-internalising reagent, using a cell line engineered to express both target antigens. These data demonstrate the applicability of the isothiocyanate group for the development of high-quality conjugates, and the use of internalising MAb to significantly increase the photodynamic efficiency of conjugates during photoimmunotherapy

Intra-oral compartment pressures: a biofunctional model and experimental measurements under different conditions of posture

Oral posture is considered to have a major influence on the development and reoccurrence of malocclusion. A biofunctional model was tested with the null hypotheses that (1) there are no significant differences between pressures during different oral functions and (2) between pressure measurements in different oral compartments in order to substantiate various postural conditions at rest by intra-oral pressure dynamics. Atmospheric pressure monitoring was simultaneously carried out with a digital manometer in the vestibular inter-occlusal space (IOS) and at the palatal vault (sub-palatal space, SPS). Twenty subjects with normal occlusion were evaluated during the open-mouth condition (OC), gently closed lips (semi-open compartment condition, SC), with closed compartments after the generation of a negative pressure (CCN) and swallowing (SW). Pressure curve characteristics were compared between the different measurement phases (OC, SC, CCN, SW) as well as between the two compartments (IOS, SPS) using analysis of variance and Wilcoxon matched-pairs tests adopting a significance level of α = 0.05. Both null hypotheses were rejected. Average pressures (IOS, SPS) in the experimental phases were 0.0, −0.08 (OC); −0.16, −1.0 (SC); −48.79, −81.86 (CCN); and −29.25, −62.51 (SW) mbar. CCN plateau and peak characteristics significantly differed between the two compartments SPS and IOS. These results indicate the formation of two different intra-oral functional anatomical compartments which provide a deeper understanding of orofacial biofunctions and explain previous observations of negative intra-oral pressures at rest

Severity-adjusted evaluation of liver transplantation on health outcomes in urea cycle disorders

Purpose: Liver transplantation (LTx) is performed in individuals with urea cycle disorders when medical management (MM) insufficiently prevents the occurrence of hyperammonemic events. However, there is a paucity of systematic analyses on the effects of LTx on health-related outcome parameters compared to individuals with comparable severity who are medically managed. Methods: We investigated the effects of LTx and MM on validated health-related outcome parameters, including the metabolic disease course, linear growth, and neurocognitive outcomes. Individuals were stratified into “severe” and “attenuated” categories based on the genotype-specific and validated in vitro enzyme activity. Results: LTx enabled metabolic stability by prevention of further hyperammonemic events after transplantation and was associated with a more favorable growth outcome compared with individuals remaining under MM. However, neurocognitive outcome in individuals with LTx did not differ from the medically managed counterparts as reflected by the frequency of motor abnormality and cognitive standard deviation score at last observation. Conclusion: Whereas LTx enabled metabolic stability without further need of protein restriction or nitrogen-scavenging therapy and was associated with a more favorable growth outcome, LTx—as currently performed—was not associated with improved neurocognitive outcomes compared with long-term MM in the investigated urea cycle disorders.</p

Transatlantic combined and comparative data analysis of 1095 patients with urea cycle disorders?A successful strategy for clinical research of rare diseases

BACKGROUND: To improve our understanding of urea cycle disorders (UCDs) prospectively followed by two North American (NA) and European (EU) patient cohorts. AIMS: Description of the NA and EU patient samples and investigation of the prospects of combined and comparative analyses for individuals with UCDs. METHODS: Retrieval and comparison of the data from 1095 individuals (NA: 620, EU: 475) from two electronic databases. RESULTS: The proportion of females with ornithine transcarbamylase deficiency (fOTC-D), particularly those being asymptomatic (asfOTC-D), was higher in the NA than in the EU sample. Exclusion of asfOTC-D resulted in similar distributions in both samples. The mean age at first symptoms was higher in NA than in EU patients with late onset (LO), but similar for those with early (</= 28 days) onset (EO) of symptoms. Also, the mean age at diagnosis and diagnostic delay for EO and LO patients were similar in the NA and EU cohorts. In most patients (including fOTC-D), diagnosis was made after the onset of symptoms (59.9%) or by high-risk family screening (24.7%), and less often by newborn screening (8.9%) and prenatal testing (3.7%). Analysis of clinical phenotypes revealed that EO patients presented with more symptoms than LO individuals, but that numbers of symptoms correlated with plasma ammonium concentrations in EO patients only. Liver transplantation was reported for 90 NA and 25 EU patients. CONCLUSIONS: Combined analysis of databases drawn from distinct populations opens the possibility to increase sample sizes for natural history questions, while comparative analysis utilizing differences in approach to treatment can evaluate therapeutic options and enhance long-term outcome studies

Bans of WHO Class I Pesticides in Bangladesh –Suicide Prevention without Hampering Agricultural Output

Pesticide self-poisoning is a major problem in Bangladesh. Over the past 20-years, the Bangladesh government has introduced pesticide legislation and banned highly hazardous pesticides (HHPs) from agricultural use. We aimed to assess the impacts of pesticide bans on suicide and on agricultural production.We obtained data on unnatural deaths from the Statistics Division of Bangladesh Police, and used negative binomial regression to quantify changes in pesticide suicides and unnatural deaths following removal of WHO Class I toxicity HHPs from agriculture in 2000. We assessed contemporaneous trends in other risk factors, pesticide usage and agricultural production in Bangladesh from 1996 to 2014.Mortality in hospital from pesticide poisoning fell after the 2000 ban: 15.1% vs 9.5%, relative reduction 37.1% [95% confidence interval (CI) 35.4 to 38.8%]. The pesticide poisoning suicide rate fell from 6.3/100 000 in 1996 to 2.2/100 000 in 2014, a 65.1% (52.0 to 76.7%) decline. There was a modest simultaneous increase in hanging suicides [20.0% (8.4 to 36.9%) increase] but the overall incidence of unnatural deaths fell from 14.0/100 000 to 10.5/100 000 [25.0% (18.1 to 33.0%) decline]. There were 35 071 (95% CI 25 959 to 45 666) fewer pesticide suicides in 2001 to 2014 compared with the number predicted based on trends between 1996 to 2000. This reduction in rate of pesticide suicides occurred despite increased pesticide use and no change in admissions for pesticide poisoning, with no apparent influence on agricultural output.Strengthening pesticide regulation and banning WHO Class I toxicity HHPs in Bangladesh were associated with major reductions in deaths and hospital mortality, without any apparent effect on agricultural output. Our data indicate that removing HHPs from agriculture can rapidly reduce suicides without imposing substantial agricultural costs

Improving outcome reporting in clinical trial reports and protocols: study protocol for the Instrument for reporting Planned Endpoints in Clinical Trials (InsPECT)

Abstract Background Inadequate and poor quality outcome reporting in clinical trials is a well-documented problem that impedes the ability of researchers to evaluate, replicate, synthesize, and build upon study findings and impacts evidence-based decision-making by patients, clinicians, and policy-makers. To facilitate harmonized and transparent reporting of outcomes in trial protocols and published reports, the Instrument for reporting Planned Endpoints in Clinical Trials (InsPECT) is being developed. The final product will provide unique InsPECT extensions to the SPIRIT (Standard Protocol Items: Recommendations for Interventional Trials) and CONSORT (Consolidated Standards of Reporting Trials) reporting guidelines. Methods The InsPECT SPIRIT and CONSORT extensions will be developed in accordance with the methodological framework created by the EQUATOR (Enhancing the Quality and Transparency of Health Research Quality) Network for reporting guideline development. Development will consist of (1) the creation of an initial list of candidate outcome reporting items synthesized from expert consultations and a scoping review of existing guidance for reporting outcomes in trial protocols and reports; (2) a three-round international Delphi study to identify additional candidate items and assess candidate item importance on a 9-point Likert scale, completed by stakeholders such as trial report and protocol authors, systematic review authors, biostatisticians and epidemiologists, reporting guideline developers, clinicians, journal editors, and research ethics board representatives; and (3) an in-person expert consensus meeting to finalize the set of essential outcome reporting items for trial protocols and reports, respectively. The consensus meeting discussions will be independently facilitated and informed by the empirical evidence identified in the primary literature and through the opinions (aggregate rankings and comments) collected via the Delphi study. An integrated knowledge translation approach will be used throughout InsPECT development to facilitate implementation and dissemination, in addition to standard post-development activities. Discussion InsPECT will provide evidence-informed and consensus-based standards focused on outcome reporting in clinical trials that can be applied across diverse disease areas, study populations, and outcomes. InsPECT will support the standardization of trial outcome reporting, which will maximize trial usability, reduce bias, foster trial replication, improve trial design and execution, and ultimately reduce research waste and help improve patient outcomes