Miracle-dz/UniFAR-FTUs huggingface dataset:
Addressing issues in health technology assessment promotion: Motives, enablers, and barriers

Objectives: The aim of this study was to analyze the motives, enablers, and barriers to promote or initiate health technology assessment (HTA) in different contexts. Methods: An observational study design was used to address the above question that included a survey questionnaire and a two-phase study. The respondents for the questionnaire and first round of the study were from HTA agencies of high income countries and those low and middle income countries that have managed to establish HTA agencies (n = 50), that are members of International Network of Agencies for Health Technology Assessment (INAHTA), EuroScan, or European network for Health Technology Assessment (EUnetHTA). The second round of the study was exclusively with respondents from low and middle income countries that were manly affiliated to Health Technology Assessment International (HTAi) interest subgroup for low and middle income countries and aimed to initiate HTA activities (n = 34). Results: Forty-one of fifty HTA agencies answered the survey questionnaire. Thirty-three of fifty individuals belonging to HTA agencies from high income countries and sixteen of thirty-four individuals from low and middle income countries answered in the first and second phases of the study, respectively. In the promotion and/or initiation of HTA, the top three motives were the same for both high income and low and middle income countries. The top three enablers were also similar but the prioritization varies. The top three barriers were more context specific. Conclusions: HTA promotion or initiation is influenced by the following: (i) key players that affect the time taken to establish HTA agencies; (ii) three models for HTA promotion and initiation: top-down (political interest), bottom-up (academic/research interest), and converging (political and academic/research interests); and (iii) motives, enablers, and barriers at the local context.
Early glomerular dysfunction in human renal allografts.

BACKGROUND The long-term outcome of renal allografts is characterized by a progressive deterioration of renal function and graft loss. Our aim was to determine early glomerular functional abnormalities, before they become clinically apparent. METHODS Glomerular hemodynamics and dextran sieving were characterized in 21 well-functioning cadaveric renal allograft recipients [normal glomerular filtration rate (GFR) and albumin excretion rate (AER), who also had a kidney biopsy with normal or minimal histological changes] and in 15 uninephrectomized kidney donors. Both groups were one to three years after transplantation or uninephrectomy. RESULTS The GFR and renal plasma flow (RPF) were similar in both groups (62 +/- 3 vs. 63 +/- 4, and 343 +/- 26 vs. 334 +/- 21 mL/min/1.73 m2 for GFR and RPF, in cadaveric recipients vs. donors, respectively), the AER was normal in both groups, but the mean arterial pressure was higher in renal recipients (103 +/- 3 vs. 94 +/- 3 mm Hg in uninephrectomy controls, P < 0.05). Despite similar levels of overall glomerular function in the two groups, the dextran sieving curve was uniformly elevated in the renal allograft recipients versus uninephrectomy controls (P < 0.05 for dextrans 38 to 66 A). Using a log-normal glomerular pore-size distribution model to analyze potential mechanisms, the elevation in the dextran sieving curve resulted from a shift in the distribution of glomerular filtering pores to a larger size (mean glomerular pore size 46 +/- 2 vs. 43 +/- 2 A for uninephrectomy controls, P < 0.05), resulting in a larger fraction of filtrate volume permeating very large pores. By morphometric analysis, the thickness of the glomerular basement membrane was increased in kidney allograft as compared to 2-kidney biopsy controls (614 +/- 33 vs. 427 +/- 22 nm, respectively, P < 0.05). CONCLUSIONS Even in "well functioning" renal allografts there is a glomerular dysfunction characterized by increased permeability to macromolecules resulting from a shift of the glomerular pores to a larger size. These changes could be mediated by ultrastructural alterations at the glomerular capillary or by alterations in intraglomerular hemodynamics. Early allograft dysfunction may contribute to the progressive renal insufficiency of renal allografts.
The Effects of Asymmetric Oil Price Shocks on the Saudi Consumption: An Empirical Investigations

The purpose of this paper is to analyze theoretically and empirically the relationship between the asymmetric oil price shock and the consumption in Saudi Arabia for the period 1985-2015.This paper follows Mehra and Petersen (2005), Zhang and Broadstock (2014), and has added a new perspective through which the oil price shocks are transmitted to consumption in the Saudi economy. The oil price shock is calculated, as SOPI, using GARCH (1,1). VAR and VEC models are applied, and the findings confirm that the oil price shocks affect positively ( +) the earnings of oil, and thereby total consumption. An increase in oil price will cause an increase in revenues, and hence consumption and vice versa. However, the decline in oil revenue on average is about (-21) percent, whereas the fall in consumption is about (-24) percent. These results coincide with the causality tests. Although, Mehra and Petersen (2005) found negative impacts of oil price shocks, our results differ in sign because this work is concerning an oil-exporting country. Keywords: Consumption, Saudi Arabia, Asymmetric shocks, and GARCH. JEL Classifications: C5, E21
Polygenic risk, stressful life events and depressive symptoms in older adults: a polygenic score analysis

Background. Previous studies suggest that the relationship between genetic risk and depression may be moderated by stressful life events (SLEs). The goal of this study was to assess whether SLEs moderate the association between polygenic risk of major depressive disorder (MDD) and depressive symptoms in older adults. Method. We used logistic and negative binomial regressions to assess the associations between polygenic risk, SLEs and depressive symptoms in a sample of 8761 participants from the Health and Retirement Study. Polygenic scores were derived from the Psychiatric Genomics Consortium genome-wide association study of MDD. SLEs were operationalized as a dichotomous variable indicating whether participants had experienced at least one stressful event during the previous 2 years. Depressive symptoms were measured using an eight-item Center for Epidemiologic Studies Depression Scale subscale and operationalized as both a dichotomous and a count variable. Results. The odds of reporting four or more depressive symptoms were over twice as high among individuals who experienced at least one SLE (odds ratio 2.19, 95% confidence interval 1.86–2.58). Polygenic scores were significantly associated with depressive symptoms (β = 0.21, p ⩽ 0.0001), although the variance explained was modest (pseudo r 2 = 0.0095). None of the interaction terms for polygenic scores and SLEs was statistically significant. Conclusions. Polygenic risk and SLEs are robust, independent predictors of depressive symptoms in older adults. Consistent with an additive model, we found no evidence that SLEs moderated the association between common variant polygenic risk and depressive symptoms.
Teachers' Commitment to, and Experiences of, the Teaching Profession in Tanzania: Findings of Focus Group Research

This qualitative study examined teachers’ commitment to, and experiences of, the teaching profession in six regions of Tanzania. The study used focus group discussions as research method and data collection tool. Twenty four groups were conducted, with group membership ranging from five to nine participants. The results show that the teachers’ commitment to the teaching profession is devastatingly low, with the majority of teachers expressing that they did not choose the teaching profession as their choice, but were compelled by the easiness to get the job and lack of qualifications to join other professions of their liking and choice. Teachers highlighted poor working environment and poor government and community attitudes towards the teaching profession as the main de-motivating factors for the teaching profession. In order to raise teachers’ commitment to the teaching profession, which is an important contributor to the students’ academic achievement, it is recommended that the Government of Tanzania and other stakeholders should improve the teachers working conditions, including provision of housing facilities and social welfare services.
Behavior of Smooth Muscle Cells during Arterial Ductal Closure at Birth

To determine which part of the smooth muscle cells (SMCs) of the ductus arteriosus (DA) contribute to duct closure after birth, we looked for areas in which SM2 myosin heavy chain (MHC) mRNA expression, which is associated with contraction of smooth muscle, and apoptosis could be detected in the DA during development. In situ hybridization revealed that the SM2 MHC mRNA was strongly positive in the longitudinally oriented SMCs and inner layer of the circularly oriented SMCsjust before birth. Apoptotic cells were detected in the SMCs of the DA from 1 day after birth. Histochemical analysis using terminal deoxynucleotidyl transferase-mediated dUTP-digoxigenin nick end-labeling (TUNEL) revealed significant numbers of TUNEL-positive nuclei in the longitudinally oriented SMCs and the inner layer of the circularly oriented SMCs. Masson-stained sections showed that the TUNEL-positive area in the DA was replaced by connective tissue from 1 day after birth. These results suggest that the increase in the SM2 MHC mRNA expression and the induction of apoptosis are present at the same site in the media of the DA. Therefore, the SMCs in this area may play an important role in duct constriction and remodeling of the vessel wall after birth.
The axotomy‐induced neuropeptides galanin and pituitary adenylate cyclase‐activating peptide promote axonal sprouting of primary afferent and cranial motor neurones

The neuropeptides galanin and pituitary adenylate cyclase‐activating peptide (PACAP) are markedly up‐regulated in response to peripheral nerve lesion. Both peptides are involved in neuronal differentiation and neurite outgrowth during development. In this study, we investigated the effects of galanin and PACAP on axonal elongation and sprouting by adult rat sensory neurones in vitro and facial motor neurones in vivo. Dissociated rat dorsal root ganglion neurones were plated on laminin substrate and analysed morphometrically. Both the mean axonal length and the number of branch points significantly increased in the presence of galanin or PACAP (2–5 µm). Effects on axonal collateralization were investigated in the rat facial nerve lesion model by direct application of the peptides to collagen‐filled conduits entubulating the transected facial nerve stumps. Triple retrograde labelling of brainstem neurones confirmed that the peptides potently induce axonal sprouting of cranial motor neurones. The number of neurones regenerating into identified rami of the facial nerve increased up to fivefold. Biometrical analysis of whisking behaviour revealed that galanin and PACAP impaired the functional outcome when compared with vehicle‐treated animals 8 weeks after surgery. In conclusion, although galanin and PACAP have been established as neurotrophic molecules with respect to axonal development and regeneration, their potential as treatments for peripheral nerve lesions appears limited because of the extensive stimulation of collateral axon branching. These branches are misrouted towards incorrect muscles and cause impairment in their coordinated activity.
Testosterone Inhibits 11-Ketotestosterone-Induced Spermatogenesis in African Catfish (Clarias gariepinus)1

Abstract Male fish produce 11-ketotestosterone as a potent androgen in addition to testosterone. Previous experiments with juvenile African catfish (Clarias gariepinus) showed that 11-ketotestosterone, but not testosterone, stimulated spermatogenesis, whereas testosterone, but not 11-ketotestosterone, accelerated pituitary gonadotroph development. Here, we investigated the effects of combined treatment with these two types of androgens on pituitary gonadotroph and testis development. Immature fish were implanted for 2 wk with silastic pellets containing 11-ketotestosterone, testosterone, 5α-dihydrotestosterone, or estradiol-17β; cotreatment groups received 11-ketotestosterone in combination with one of the other steroids. Testicular weight and pituitary LH content were higher (two- and fivefold, respectively) in the end control than in the start control group, reflecting the beginning of normal pubertal development. Treatment with testosterone or estradiol-17β further increased the pituitary LH content four- to sixfold above the end control levels. This stimulatory effect on the pituitary LH content was not modulated by cotreatment with 11-ketotestosterone. However, the stimulatory effect of 11-ketotestosterone on testis growth and spermatogenesis was abolished by cotreatment with testosterone, but not by cotreatment with estradiol-17β or 5α-dihydrotestosterone. Also, normal pubertal testis development was inhibited by prolonged (4 wk) treatment with testosterone. The inhibitory effect of testosterone may involve feedback effects on pituitary FSH and/or on FSH receptors in the testis. It appears that the balanced production of two types of androgens, and the control of their biological activities, are critical to the regulation of pubertal development in male African catfish.
Towards improved hardware component attenuation correction in PET/MR hybrid imaging

In positron emission tomography/computed tomography (PET/CT) hybrid imaging attenuation correction (AC) of the patient tissue and patient table is performed by converting the CT-based Hounsfield units (HU) to linear attenuation coefficients (LAC) of PET. When applied to the new field of hardware component AC in PET/magnetic resonance (MR) hybrid imaging, this conversion method may result in local overcorrection of PET activity values. The aim of this study thus was to optimize the conversion parameters for CT-based AC of hardware components in PET/MR. Systematic evaluation and optimization of the HU to LAC conversion parameters has been performed for the hardware component attenuation map (µ-map) of a flexible radiofrequency (RF) coil used in PET/MR imaging. Furthermore, spatial misregistration of this RF coil to its µ-map was simulated by shifting the µ-map in different directions and the effect on PET quantification was evaluated. Measurements of a PET NEMA standard emission phantom were performed on an integrated hybrid PET/MR system. Various CT parameters were used to calculate different µ-maps for the flexible RF coil and to evaluate the impact on the PET activity concentration. A 511 keV transmission scan of the local RF coil was used as standard of reference to adapt the slope of the conversion from HUs to LACs at 511 keV. The average underestimation of the PET activity concentration due to the non-attenuation corrected RF coil in place was calculated to be 5.0% in the overall phantom. When considering attenuation only in the upper volume of the phantom, the average difference to the reference scan without RF coil is 11.0%. When the PET/CT conversion is applied, an average overestimation of 3.1% (without extended CT scale) and 4.2% (with extended CT scale) is observed in the top volume of the NEMA phantom. Using the adapted conversion resulting from this study, the deviation in the top volume of the phantom is reduced to −0.5% and shows the lowest standard deviation inside the phantom in comparison to all other conversions. Simulation of a µ-map misregistration shows acceptable results for shifts below 5 mm for the flexible surface RF coil. The adapted conversion from HUs to LAC at 511 keV within this study can improve hardware component AC in PET/MR hybrid imaging as shown for a flexible RF surface coil. Furthermore, these results have a direct impact on the improvement of the hardware component AC of the examined flexible RF coil in conjunction with position determination.
Robust Evaluation of Multivariate Density Forecasts

We derive new tests for proper calibration of multivariate density forecasts based on Rosenblatt probability integral transforms. These tests have the advantage that they i) do not depend on the ordering of variables in the forecasting model, ii) are applicable to densities of arbitrary dimensions, and iii) have superior power relative to existing approaches. We furthermore develop adjusted tests that allow for estimated parameters and, consequently, can be used as in-sample specification tests. We demonstrate the problems of existing tests and how our new approaches can overcome those using two applications based on multivariate GARCH-based models for stock market returns and on a macroeconomic Bayesian vectorautoregressive model.
A time‐sequence functional analysis of mating behaviour and genital coupling in Drosophila: role of cryptic female choice and male sex‐drive in the evolution of male genitalia

Male genitalia in Drosophila exemplify strikingly rapid and divergent evolution, whereas female genitalia are relatively invariable. Whereas precopulatory and post‐copulatory sexual selection has been invoked to explain this trend, the functional significance of genital structures during copulation remains obscure. We used time‐sequence analysis to study the functional significance of external genitalic structures during the course of copulation, between D. melanogaster and D. simulans. This functional analysis has provided new information that reveals the importance of male‐driven copulatory mechanics and strategies in the rapid diversification of genitalia. The posterior process, which is a recently evolved sexual character and present only in males of the melanogaster clade, plays a crucial role in mounting as well as in genital coupling. Whereas there is ample evidence for precopulatory and/or post‐copulatory female choice, we show here that during copulation there is little or no physical female choice, consequently, males determine copulation duration. We also found subtle differences in copulatory mechanics between very closely related species. We propose that variation in male usage of novel genitalic structures and shifts in copulatory behaviour have played an important role in the diversification of genitalia in species of the Drosophila subgroup.
Anastomotic Leakage of a Colorectal Anastomosis Treated by Transanal Endoscopic Microsurgery

Abstract Objective: To report a minimal invasive technique for repairing an anastomotic leakage with Transanal Endoscopic Microsurgery (T.E.M.) without creating a protective ostomy. Summary: There are a large number of techniques for the management of anastomotic leakage after colorectal surgery. Depending on the size and location of the disruption, a protective ileostomy, a permanent colostomy or even reïnterven-tion for drainage or closure of the leak may be indicated. In most cases the patient faces the morbidity associated with a new intervention, a prolonged hospital stay and a future operation for closure of the stoma. In the present case a 56-year-old man underwent a laparoscopic rectosigmoid resection after two episodes of diverticulitis in six months. An end-to-end circular stapled anastomosis was constructed. Unfortunately 8-days postoperatively an anastomotic leak occurred. Attempts to close the tear non-surgically with colonoscopy and clipping failed. A minimally invasive reintervention with transanal endoscopic microsurgery (T.E.M.) was performed without creation of an ileostomy. One week postoperatively a gastrografin bowel study showed no leakage. To our knowledge, this technique has not yet been reported without the simultaneous construction of a stoma. Conclusion: We describe a possible minimally invasive technique to avoid laparotomy and/or the creation of a derivative stoma in the management of anastomotic leakage. Hospital stay is not significantly prolonged, future reïntervention for closure of stoma is avoided and sphincter function is preserved.
Somatostatin Receptor Type 2–Based Reporter Expression after Plasmid-Based in Vivo Gene Delivery to Non–Small Cell Lung Cancer

Plasmids tend to have much lower expression than viruses. Gene expression after systemic administration of plasmid vectors has not been assessed using somatostatin receptor type 2 (SSTR2)-based reporters. The purpose of this work was to identify gene expression in non–small cell lung cancer (NSCLC) after systemic liposomal nanoparticle delivery of plasmid containing SSTR2-based reporter gene. In vitro, Western blotting was performed after transient transfection with the plasmid cytomegalovirus (CMV)-SSTR2, CMV-TUSC2-IRES-SSTR2, or CMV-TUSC2. SSTR2 is the reporter gene, and TUSC2 is a therapeutic gene. Mice with A549 NSCLC lung tumors were injected intravenously with CMV-SSTR2, CMV-TUSC2-IRES-SSTR2, or CMV-TUSC2 plasmids in DOTAP:cholesterolliposomal nanoparticles. Two days later, mice were injected intravenously with 111In-octreotide. The next day, biodistribution was performed. The experiment was repeated including single-photon emission computed tomography/computed tomography (SPECT/CT). Immunohistochemistry was performed. In vitro, SSTR2 expression was similar in cells transfected with CMV-SSTR2 or CMV-TUSC2-IRES-SSTR2. TUSC2 expression was similar in cells transfected with CMV-TUSC2 or CMV-TUSC2-SSTR2. Biodistribution demonstrated significantly greater 111In-octreotide uptake in tumors from mice injected with CMV-TUSC2-IRES-SSTR2 or CMV-SSTR2 than the control plasmid, CMV-TUSC2 (p < .05). Gamma-camera and SPECT/CT imaging illustrated SSTR2 expression in tumors in mice injected with CMV-TUSC2-IRES-SSTR2 or CMV-SSTR2 versus background with control plasmid. Immunohistochemistry corresponded with imaging. SSTR2-based reporter imaging can visualize gene expression in lung tumors after systemic liposomal nanoparticle delivery of plasmid containing SSTR2-based reporter gene or SSTR2 linked to a second therapeutic gene, such as TUSC2.