Reputation and Competence in Publicly Funded Science: Estimating the Effects on Research Group Productivity..

This paper estimates the "production function" for scientific research publications in the field of biotechnology. It utilizes an exceptionally rich and comprehensive data set pertaining to the universe of research groups that applied to a 1989-1993 research program in biotechnology and bio-instrumentation, sponsored by the Italian National research Council, CNR. A structural model of the resource allocation process in scientific research guides the selection of instruments in the econometric analysis, and controls for selectivity bias effects on estimates based on the performance of funded research units. The average elasticity of research output with respect to the research budget is estimated to be 0.6; but, for a small fraction of groups led by highly prestigious PIs this elasticity approaches 1. These estimates imply, conditional on the distribution of observed productivity, that a more unequal distribution of research funds would increase research output in the short-run. Past research publication performance is found to have an important effect on expect levels of grant funding, and hence on the unit's current productivity in terms of (quality adjusted) publications. The results show that the productivity of aggregate resource expenditures supporting scientific research is critically dependent on the institutional mechanisms and criteria employed in the allocation of such resources.

X-ray CT analysis after blast of composite sandwich panels

Four composite sandwich panels with either single density or graded density foam cores and different face-sheet materials were subjected to full-scale underwater blast testing. The panels were subjected to 1kg PE4 charge at a stand-off distance of 1 m. The panel with graded density core and carbon fiber face-sheets had the lowest deflection. Post-blast damage assessment was carried out using X-ray CT scanning. The damage assessment revealed that there is a trade-off between reduced panel deflection and panel damage. This research has been performed as part of a program sponsored by the Office of Naval Research (ONR)

Failure analysis using X-ray computed tomography of composite sandwich panels subjected to full-scale blast loading

The tailorable mechanical properties and high strength-to-weight ratios of composite sandwich panels make them of interest to the commercial marine and naval sector, however, further investigation into their blast resilience is required. The experiments performed in this study aimed to identify whether alterations to the composite skins or core of a sandwich panel can yield improved blast resilience both in air and underwater. Underwater blast loads using 1.28 kg TNT equivalent charge at a stand-off distance of 1 m were performed on four different composite sandwich panels. Results revealed that implementing a stepwise graded density foam core, with increasing density away from the blast, reduces the deflection of the panel and damage sustained. Furthermore, the skin material affects the extent of panel deflection and damage, the lower strain to failure of carbon-fibre reinforced polymer (CFRP) skins reduces deflection but increases skin debonding. A further two panels were subjected to a 100 kg TNT air blast loading at a 15 m stand-off to compare the effect of a graded density core and the results support the underwater blast results. Future modelling of these experiments will aid the design process and should aim to include material damage mechanisms to identify the most suitable skins

Elevated CO₂ does not increase eucalypt forest productivity on a low-phosphorus soil

Rising atmospheric CO2 stimulates photosynthesis and productivity of forests, offsetting CO2 emissions. Elevated CO2 experiments in temperate planted forests yielded ~23% increases in productivity over the initial years. Whether similar CO2 stimulation occurs in mature evergreen broadleaved forests on low-phosphorus (P) soils is unknown, largely due to lack of experimental evidence. This knowledge gap creates major uncertainties in future climate projections as a large part of the tropics is P-limited. Here,we increased atmospheric CO2 concentration in a mature broadleaved evergreen eucalypt forest for three years, in the first large-scale experiment on a P-limited site. We show that tree growth and other aboveground productivity components did not significantly increase in response to elevated CO2 in three years, despite a sustained 19% increase in leaf photosynthesis. Moreover, tree growth in ambient CO2 was strongly P-limited and increased by ~35% with added phosphorus. The findings suggest that P availability may potentially constrain CO2-enhanced productivity in P-limited forests; hence, future atmospheric CO2 trajectories may be higher than predicted by some models. As a result, coupled climate-carbon models should incorporate both nitrogen and phosphorus limitations to vegetation productivity in estimating future carbon sinks

The Rise and Fall of HIV in High-Prevalence Countries: A Challenge for Mathematical Modeling

Several countries with generalized, high-prevalence HIV epidemics, mostly in sub-Saharan Africa, have experienced rapid declines in transmission. These HIV epidemics, often with rapid onsets, have generally been attributed to a combination of factors related to high-risk sexual behavior. The subsequent declines in these countries began prior to widespread therapy or implementation of any other major biomedical prevention. This change has been construed as evidence of behavior change, often on the basis of mathematical models, but direct evidence for behavior changes that would explain these declines is limited. Here, we look at the structure of current models and argue that the common "fixed risk per sexual contact" assumption favors the conclusion of substantial behavior changes. We argue that this assumption ignores reported non-linearities between exposure and risk. Taking this into account, we propose that some of the decline in HIV transmission may be part of the natural dynamics of the epidemic, and that several factors that have traditionally been ignored by modelers for lack of precise quantitative estimates may well hold the key to understanding epidemiologic trends

Adverse prognostic and predictive significance of low DNA-dependent protein kinase catalytic subunit (DNA-PKcs) expression in early-stage breast cancers

Background: DNA-dependent protein kinase catalytic subunit (DNA-PKcs), a serine threonine kinase belonging to the PIKK family (phosphoinositide 3-kinase-like-family of protein kinase), is a critical component of the non-homologous end joining (NHEJ) pathway required for the repair of DNA double strand breaks. DNA-PKcs may be involved in breast cancer pathogenesis. Methods: We evaluated clinicopathological significance of DNA-PKcs protein expression in 1161 tumours and DNA-PKcs mRNA expression in 1950 tumours. We correlated DNA-PKcs to other markers of aggressive phenotypes, DNA repair, apoptosis and cell cycle regulation. Results: Low DNA-PKcs protein expression was associated with higher tumour grade, higher mitotic index, tumour de-differentiation and tumour type (ps<0.05). Absence of BRCA1, low XRCC1/SMUG1/APE1/Polβ were also more likely in low DNA-PKcs expressing tumours (ps<0.05). Low DNA-PKcs protein expression was significantly associated with worse breast cancer specific survival (BCCS) in univariate and multivariate analysis (ps<0.01). At the mRNA level, low DNA-PKcs was associated with PAM50.Her2 and PAM50.LumA molecular phenotypes (ps<0.01) and poor BCSS. In patients with ER positive tumours who received endocrine therapy, low DNA-PKcs (protein and mRNA) was associated with poor survival. In ER negative patients, low DNA-PKcs mRNA remains significantly associated with adverse outcome. Conclusions: Our study suggests that low DNA-PKcs expression may have prognostic and predictive significance in breast cancers

Temporal dystrophic remodeling within the intrinsic cardiac nervous system of the streptozotocin-induced diabetic rat model

INTRODUCTION: The pathogenesis of heart failure (HF) in diabetic individuals, called “diabetic cardiomyopathy”, is only partially understood. Alterations in the cardiac autonomic nervous system due to oxidative stress have been implicated. The intrinsic cardiac nervous system (ICNS) is an important regulatory pathway of cardiac autonomic function, however, little is known about the alterations that occur in the ICNS in diabetes. We sought to characterize morphologic changes and the role of oxidative stress within the ICNS of diabetic hearts. Cultured ICNS neuronal cells from the hearts of 3- and 6-month old type 1 diabetic streptozotocin (STZ)-induced diabetic Sprague-Dawley rats and age-matched controls were examined. Confocal microscopy analysis for protein gene product 9.5 (PGP 9.5) and amino acid adducts of (E)-4-hydroxy-2-nonenal (4-HNE) using immunofluorescence was undertaken. Cell morphology was then analyzed in a blinded fashion for features of neuronal dystrophy and the presence of 4-HNE adducts. RESULTS: At 3-months, diabetic ICNS neuronal cells exhibited 30% more neurite swellings per area (p = 0.01), and had a higher proportion with dystrophic appearance (88.1% vs. 50.5%; p = <0.0001), as compared to control neurons. At 6-months, diabetic ICNS neurons exhibited more features of dystrophy as compared to controls (74.3% vs. 62.2%; p = 0.0448), with 50% more neurite branching (p = 0.0015) and 50% less neurite outgrowth (p = <0.001). Analysis of 4-HNE adducts in ICNS neurons of 6-month diabetic rats demonstrated twice the amount of reactive oxygen species (ROS) as compared to controls (p = <0.001). CONCLUSION: Neuronal dystrophy occurs in the ICNS neurons of STZ-induced diabetic rats, and accumulates temporally within the disease process. In addition, findings implicate an increase in ROS within the neuronal processes of ICNS neurons of diabetic rats suggesting an association between oxidative stress and the development of dystrophy in cardiac autonomic neurons

Development and validation of a Hospital Frailty Risk Score focusing on older people in acute care settings using electronic hospital records: an observational study

Background Older people are increasing users of health care globally. We aimed to establish whether older people with characteristics of frailty and who are at risk of adverse health-care outcomes could be identified using routinely collected data. Methods A three-step approach was used to develop and validate a Hospital Frailty Risk Score from International Statistical Classification of Diseases and Related Health Problems, Tenth Revision (ICD-10) diagnostic codes. First, we carried out a cluster analysis to identify a group of older people (≥75 years) admitted to hospital who had high resource use and diagnoses associated with frailty. Second, we created a Hospital Frailty Risk Score based on ICD-10 codes that characterised this group. Third, in separate cohorts, we tested how well the score predicted adverse outcomes and whether it identified similar groups as other frailty tools. Findings In the development cohort (n=22 139), older people with frailty diagnoses formed a distinct group and had higher non-elective hospital use (33·6 bed-days over 2 years compared with 23·0 bed-days for the group with the next highest number of bed-days). In the national validation cohort (n=1 013 590), compared with the 429 762 (42·4%) patients with the lowest risk scores, the 202 718 (20·0%) patients with the highest Hospital Frailty Risk Scores had increased odds of 30-day mortality (odds ratio 1·71, 95% CI 1·68–1·75), long hospital stay (6·03, 5·92–6·10), and 30-day readmission (1·48, 1·46–1·50). The c statistics (ie, model discrimination) between individuals for these three outcomes were 0·60, 0·68, and 0·56, respectively. The Hospital Frailty Risk Score showed fair overlap with dichotomised Fried and Rockwood scales (kappa scores 0·22, 95% CI 0·15–0·30 and 0·30, 0·22–0·38, respectively) and moderate agreement with the Rockwood Frailty Index (Pearson's correlation coefficient 0·41, 95% CI 0·38–0·47)

Mapping of Mycobacterium tuberculosis Complex Genetic Diversity Profiles in Tanzania and Other African Countries

The aim of this study was to assess and characterize Mycobacterium tuberculosis complex (MTBC) genotypic diversity in Tanzania, as well as in neighbouring East and other several African countries. We used spoligotyping to identify a total of 293 M. tuberculosis clinical isolates (one isolate per patient) collected in the Bunda, Dar es Salaam, Ngorongoro and Serengeti areas in Tanzania. The results were compared with results in the SITVIT2 international database of the Pasteur Institute of Guadeloupe. Genotyping and phylogeographical analyses highlighted the predominance of the CAS, T, EAI, and LAM MTBC lineages in Tanzania. The three most frequent Spoligotype International Types (SITs) were: SIT21/CAS1-Kili (n = 76; 25.94%), SIT59/LAM11-ZWE (n = 22; 7.51%), and SIT126/EAI5 tentatively reclassified as EAI3-TZA (n = 18; 6.14%). Furthermore, three SITs were newly created in this study (SIT4056/EAI5 n = 2, SIT4057/T1 n = 1, and SIT4058/EAI5 n = 1). We noted that the East-African-Indian (EAI) lineage was more predominant in Bunda, the Manu lineage was more common among strains isolated in Ngorongoro, and the Central-Asian (CAS) lineage was more predominant in Dar es Salaam (p-value<0.0001). No statistically significant differences were noted when comparing HIV status of patients vs. major lineages (p-value = 0.103). However, when grouping lineages as Principal Genetic Groups (PGG), we noticed that PGG2/3 group (Haarlem, LAM, S, T, and X) was more associated with HIV-positive patients as compared to PGG1 group (Beijing, CAS, EAI, and Manu) (p-value = 0.03). This study provided mapping of MTBC genetic diversity in Tanzania (containing information on isolates from different cities) and neighbouring East African and other several African countries highlighting differences as regards to MTBC genotypic distribution between Tanzania and other African countries. This work also allowed underlining of spoligotyping patterns tentatively grouped within the newly designated EAI3-TZA lineage (remarkable by absence of spacers 2 and 3, and represented by SIT126) which seems to be specific to Tanzania. However, further genotyping information would be needed to confirm this specificity