Miracle-dz/UniFAR-FTUs huggingface dataset:
Prognostic value of isolated nocturnal hypertension on ambulatory measurement in 8711 individuals from 10 populations

Background We and other investigators previously reported that isolated nocturnal hypertension on ambulatory measurement (INH) clustered with cardiovascular risk factors and was associated with intermediate target organ damage. We investigated whether INH might also predict hard cardiovascular endpoints. Methods and results We monitored blood pressure (BP) throughout the day and followed health outcomes in 8711 individuals randomly recruited from 10 populations (mean age 54.8 years, 47.0% women). Of these, 577 untreated individuals had INH (daytime BP <135/85 mmHg and night-time BP ≥120/70 mmHg) and 994 untreated individuals had isolated daytime hypertension on ambulatory measurement (IDH; daytime BP ≥135/85 mmHg and night-time BP <120/70 mmHg). During follow-up (median 10.7 years), 1284 deaths (501 cardiovascular) occurred and 1109 participants experienced a fatal or nonfatal cardiovascular event. In multivariable-adjusted analyses, compared with normotension (n = 3837), INH was associated with a higher risk of total mortality (hazard ratio 1.29, P = 0.045) and all cardiovascular events (hazard ratio 1.38, P = 0.037). IDH was associated with increases in all cardiovascular events (hazard ratio 1.46, P = 0.0019) and cardiac endpoints (hazard ratio 1.53, P = 0.0061). Of 577 patients with INH, 457 were normotensive (<140/90 mmHg) on office BP measurement. Hazard ratios associated with INH with additional adjustment for office BP were 1.31 (P = 0.039) and 1.38 (P = 0.044) for total mortality and all cardiovascular events, respectively. After exclusion of patients with office hypertension, these hazard ratios were 1.17 (P = 0.31) and 1.48 (P = 0.034). Conclusion INH predicts cardiovascular outcome in patients who are normotensive on office or on ambulatory daytime BP measurement.
Adhesion of normal erythrocytes at depressed venous shear rates to activated neutrophils, activated platelets, and fibrin polymerized from plasma.

Deep vein thrombosis (DVT) is a low flow pathology often prevented by vascular compression to increase blood movement. We report new heterotypic adhesive interactions of normal erythrocytes operative at low wall shear rates (gamma(w)) below 100 s(-1). Adhesion at gamma(w) = 50 s(-1) of washed red blood cells (RBCs) to fibrinogen-adherent platelets was 4-fold less (P <.005) than to collagen-adherent platelets (279 +/- 105 RBC/mm(2)). This glycoprotein VI (GPVI)-triggered adhesion was antagonized (> 80% reduction) by soluble fibrinogen (3 mg/mL) and ethylenediaminetetraacetic acid (EDTA). RBC-platelet adhesion was reduced in half by antibodies against CD36 or GPIb, but not by antibodies against GPIIb/IIIa, von Willebrand factor (VWF), thrombospondin (TSP), P-selectin, beta(1), alpha(v), or CD47. Adhesion of washed RBCs to fibrinogen-adherent neutrophils was increased 6-fold in the presence of 20 microM N-formyl-Met-Leu-Phe to a level of 67 RBCs per 100 neutrophils after 5 minutes at 50 s(-1). RBC-neutrophil adhesion was diminished by anti-CD11b (76%), anti-RBC Landsteiner-Wiener (LW) (ICAM4; 40%), or by EDTA (> 80%), but not by soluble fibrinogen or antibodies against CD11a, CD11c, CD36, TSP, beta(1), alpha(v), or CD47. RBC adhesion to activated platelets and activated neutrophils was prevented by wall shear stress above 1 dyne/cm(2) (at 100 s(-1)). Whereas washed RBCs did not adhere to fibrin formed from purified fibrinogen, adhesion was marked when pure fibrin was precoated with TSP or when RBCs were perfused over fibrin formed from recalcified plasma. Endothelial activation and unusually low flow may be a setting prone to receptor-mediated RBC adhesion to adherent neutrophils (or platelets/fibrin), all of which may contribute to DVT.
An equivalent circuit model for reconfigurable reflectarrays based on Floquet modal expansion

In order to design a reconfigurable reflectarray antenna, the phase of the scattered field from each element needs to be accurately determined. This paper presents an equivalent circuit model to compute the reflection coefficient of a desired Floquet mode in reconfigurable reflectarray unit cell, based on a Floquet modal expansion. The model allows for fast and easy predictions of the reflectarray curve without the need to run full-wave simulations.
Relationship Between Antiretroviral Prescribing Patterns and Treatment Guidelines in Treatment-Naive HIV-1-Infected US Veterans (1992-2004)

Objective:To analyze temporal patterns of antiretroviral (ARV) prescribing practices relative to nationally defined guidelines in treatment-naive patients with HIV-1 infection. Design:Retrospective cohort study. Methods:We evaluated ARV prescribing patterns among ARV treatment-naive veterans who were receiving care within the US Department of Veterans Affairs (VA) from 1992 through 2004 in comparison to evolving adult HIV-1 treatment guidelines. Results:A total of 15,934 patients initiated ARV treatment. Since 1999, >94% of patients initiated at least a 3-ARV medication combination, although the percentage of patients who initiated a guideline “preferred” or “alternative” regimen never rose to greater than 72% and was significantly associated with being black and with region of care. After 1999, 20% of patients started 4 or more active ARV agents in combination, which was significantly associated with lower baseline CD4 cell count, higher viral load, and receiving care in the western United States. The proportion of patients receiving guideline “not recommended” regimens (virologically undesirable or overlapping toxicities) was <1% after 1997. VA prescribing trends generally predated guideline recommendations by 6 to 12 months. Conclusions:VA prescribing patterns for ARV initiation adhere to treatment guidelines that maximize safety. Guidelines designed to maximize efficacy were not followed as stringently. Evaluating clinical practice patterns against contemporary treatment guidelines can inform guideline development.
Comparison of Effects of Compost Amendment and of Single-Strain Inoculation on Root Bacterial Communities of Young Cucumber Seedlings

ABSTRACT Compost amendment and inoculations with specific microorganisms are fundamentally different soil treatment methods, commonly used in agriculture for the improvement of plant growth and health. Although distinct, both methods affect the rhizosphere and the plant roots. In the present study we used a 16S rRNA gene approach to achieve an overview of early consequences of these treatments on the assemblage of plant root bacterial communities. For this purpose, cucumber seedlings were grown, under controlled conditions, in perlite potting mix amended with biosolid compost or straw compost, or inoculated with Streptomyces spp. A uniform trend of response of root bacterial communities for all treatments was observed. Root bacterial density, measured as bacterial targets per plant tef gene by real-time PCR, was reduced in 31 to 67%. In addition, increased taxonomic diversity accompanied shifts in composition (α-diversity). The magnitude of change in these parameters relative to the perlite control varied between the different treatments but not in relation to the treatment method (compost amendments versus inoculations). Similarity between the compositions of root and of potting mix bacterial communities (β-diversity) was relatively unchanged. The abundance of Oxalobacteraceae was >50% of the total root bacterial community in the untreated perlite. Root domination by this group subsided >10-fold (straw compost) to >600-fold (Streptomyces sp. strain S1) after treatment. Thus, loss of dominance appears to be the major phenomenon underlining the response trend of the root bacterial communities.
Treatment of epilepsy for people with Alzheimer's disease.

BACKGROUND Any type of seizure can be observed in Alzheimer's disease (AD). Antiepileptic drugs seem to prevent the recurrence of epileptic seizures in most people with AD. There are pharmacological and non-pharmacological treatments for epilepsy in people with AD. There are no current systematic reviews to evaluate the efficacy and tolerability of these treatments; this review aims to review those different modalities. This is an updated version of the original Cochrane Review published in Issue 11, 2016. OBJECTIVES To assess the efficacy and tolerability of pharmacological or non-pharmacological interventions for the treatment of epilepsy in people with AD (including sporadic AD and dominantly inherited AD). SEARCH METHODS For the latest update, on 10 July 2018 we searched the Cochrane Register of Studies (CRS Web), which includes the Cochrane Epilepsy Group's Specialized Register and the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE (Ovid 1946- ), ClinicalTrials.gov, and the WHO International Clinical Trials Registry Platform (ICTRP). In an effort to identify further published, unpublished and ongoing trials, we searched ongoing trials registers, reference lists and relevant conference proceedings, and contacted authors and pharmaceutical companies. SELECTION CRITERIA We included randomized and quasi-randomized controlled trials investigating treatment for epilepsy in people with AD, with the outcomes of proportion of participants with seizure freedom or proportion of participants experiencing adverse events. DATA COLLECTION AND ANALYSIS Two review authors independently screened the titles and abstracts of identified records, selected studies for inclusion, extracted data, cross-checked the data for accuracy and assessed the methodological quality. We performed no meta-analyses due to the limited available data. MAIN RESULTS We included one randomized controlled trial on pharmacological interventions with 95 participants. No studies were found for non-pharmacological interventions. Concerning the proportion of participants with seizure freedom, no significant differences were found for the comparisons of levetiracetam (LEV) versus lamotrigine (LTG) (risk ratio (RR) 1.20, 95% confidence interval (CI) 0.53 to 2.71), LEV versus phenobarbital (PB) (RR 1.01, 95% CI 0.47 to 2.19), or LTG versus PB (RR 0.84, 95% CI 0.35 to 2.02). It seemed that LEV could improve cognition and LTG could relieve depression, while PB and LTG could worsen cognition, and LEV and PB could worsen mood. Unclear risk of bias was found in allocation, blinding and selective reporting. We judged the quality of the evidence to be very low. AUTHORS' CONCLUSIONS This review does not provide sufficient evidence to support LEV, PB or LTG for the treatment of epilepsy in people with AD. Regarding efficacy and tolerability, no significant differences were found between LEV, PB and LTG. Large randomized controlled trials with a double-blind, parallel-group design are required to determine the efficacy and tolerability of treatment for epilepsy in people with AD.
A randomized double-blind sham-controlled comparison of unilateral and bilateral repetitive transcranial magnetic stimulation for treatment-resistant major depression

Abstract Objectives. High frequency left-sided (HFL) and low frequency right-sided (LFR) unilateral repetitive transcranial magnetic stimulation (rTMS) are efficacious in treatment-resistant major depression (TRD). Similar benefit has been suggested for sequential bilateral rTMS (LFR then HFL). There are few published reports on the efficacy of sequential bilateral rTMS compared to HFL and sham rTMS. Therefore, this study evaluated the efficacy of HFL and sequential bilateral rTMS compared to sham in TRD. Methods. Subjects between the ages of 18 and 85 were recruited from a tertiary care university hospital. Seventy-four subjects with TRD and a 17-item Hamilton Depression Rating Scale (HDRS) greater than 21 were randomized to receive unilateral, bilateral, or sham rTMS. The rates of remission were compared among the three treatment groups. Results. The remission rates differed significantly among the three treatment groups using a modified intention to treat analysis that excluded subjects who did not respond to electroconvulsive therapy (ECT) during the current episode. The remission rate was significantly higher in the bilateral group than the sham group. The remission rate in the unilateral group did not differ from either group. Conclusion. These findings warrant larger controlled studies that compare the efficacy of sequential bilateral rTMS and HFL rTMS in TRD.
Characterization of Rat Follistatin-Related Gene: Effects of Estrous Cycle Stage and Pregnancy on Its Messenger RNA Expression in Rat Reproductive Tissues1

Abstract Follistatin-related gene (FLRG) was first identified as a target of a chromosomal translocation in a human B-cell leukemia. Because FLRG protein binds to activins and bone morphogenetic proteins, FLRG is postulated to be a regulator of these growth factors. However, physiological aspects of FLRG are unclear. To elucidate the physiology of FLRG, we examined expression of FLRG in reproductive tissues of the rat. FLRG mRNA was abundantly expressed in the placenta. FLRG mRNA was also expressed in the ovary, uterus, testis, lung, adrenal gland, pituitary, kidney, small intestine, and heart. During the second half of pregnancy, expression of FLRG in the placenta continuously increased, whereas follistatin mRNA levels decreased from Day 12 to Day 14 and remained low thereafter. FLRG was also expressed in decidua. Levels of decidual FLRG mRNA remained low from Day 12 to Day 16 and then noticeably increased until Day 20. In contrast, follistatin mRNA was highly expressed in the decidua on Day 12, continuously decreased until Day 16, and then remained at relatively low levels thereafter. During the rat estrous cycle, levels of ovarian FLRG mRNA fluctuated diurnally, with highest levels during daytime, and did not change relative to the day of the estrous cycle. The present results suggest that FLRG may play a role in the regulation of reproductive events.
Revised Neurobehavioral Scales of the MMPI: Sensitivity and Specificity in Traumatic Brain Injury

The ability of 23 previously identified Minnesota Multiphasic Personality Inventory (MMPI) "neurologic content" items to distinguish between individuals with traumatic brain injury (TBI; n = 32) or spinal cord injury (SCI; n = 17) was examined. Principal-components analysis of the 23 items revealed three conceptually coherent, nonoverlapping, and uncorrelated factors (Cognitive, Somatic, Inactivity) that together accounted for 44% of the total variance. Coefficients of internal consistency for the factors were in the moderate to high range. Together, the factors were named the Revised Neurobehavioral Scales of the MMPI. The group with TBI scored significantly higher on the Cognitive scale and significantly lower on the Inactivity scale than the group with SCI (with or without depression as a covariate). The Glasgow Coma Scale correlated significantly and negatively with the Cognitive scale in the group with TBI. Discriminant function analysis revealed that together the scales correctly classified individuals with sensitivity and a positive predictive value (with respect to TBI) of 87% and 81%, respectively. Specificity and a negative predictive value (with respect to SCI) were 68% and 76%, respectively. The overall rate of correct classification of individual cases was 80% (with or without depression in the analysis). The Cognitive scale alone correctly classified individuals in the group with TBI with a positive predictive value of 84%. Findings are discussed in terms of the discriminative validity and potential utility of TBI-related MMPI items, as well as the issue of "neurocorrection" of the MMPI (or MMPI-2) in verified cases of TBI.
Strategic Biopharmaceutical Portfolio Development: An Analysis of Constraint‐Induced Implications

Optimizing the structure and development pathway of biopharmaceutical drug portfolios are core concerns to the developer that come with several attached complexities. These include strategic decisions for the choice of drugs, the scheduling of critical activities, and the possible involvement of third parties for development and manufacturing at various stages for each drug. Additional complexities that must be considered include the impact of making such decisions in an uncertain environment. Presented here is the development of a stochastic multi‐objective optimization framework designed to address these issues. The framework harnesses the ability of Bayesian networks to characterize the probabilistic structure of superior decisions via machine learning and evolve them to multi‐objective optimality. Case studies that entailed three‐ and five‐drug portfolios alongside a range of cash flow constraints were constructed to derive insight from the framework where results demonstrate that a variety of options exist for formulating nondominated strategies in the objective space considered, giving the manufacturer a range of pursuable options. In all cases limitations on cash flow reduce the potential for generating profits for a given probability of success. For the sizes of portfolio considered, results suggest that naïvely applying strategies optimal for a particular size of portfolio to a portfolio of another size is inappropriate. For the five‐drug portfolio the most preferred means for development across the set of optimized strategies is to fully integrate development and commercial activities in‐house. For the three‐drug portfolio, the preferred means of development involves a mixture of in‐house, outsourced, and partnered activities. Also, the size of the portfolio appears to have a larger impact on strategy and the quality of objectives than the magnitude of cash flow constraint.
The morphology of group Ia afferent fibre collaterals in the spinal cord of the cat.

1. The enzyme horseradish peroxidase (HRP) was injected into single Ia muscle afferent fibres in anaesthetized cats. Subsequent histochemistry allowed the morphology of the axons and their collaterals in the lumbosacral spinal cord to be determined. 2. Fifteen Ia axons were stained, four from medial gastrocnemius, four from lateral gastrocnemius‐soleus and seven from muscles innervated by the posterior tibial nerve. All thirteen axons that could be traced into the dorsal roots bifurcated upon entering the cord. Between 4 and 11 mm of axons were stained and they gave off eighty seven collaterals over distances between 3 and 9 mm. Collaterals were given off at intervals of 100‐2600 micron at an average spacing of about 1000 micron. 3. All Ia collaterals had a characteristic morphology. After leaving the parent axon they ran ventrally to lamina VI and then ventrolaterally to the motor nuclei. The collaterals coursed cranially from their point of origin to the motor nuclei so that their lamina VI terminations were about 100‐300 micro caudal to their terminations in motor nuclei. Terminal arborizations were limited to three sites; lamina VI (the intermediate region), lamina VII (the Ia inhibitory interneurone region) and lamina IX (the motor nuclei). The three sets of terminals had characteristic arborizations and bouton arrangements. 4. The results are discussed in relation to previous anatomical studies. In particular the present results suggest that a single Ia collateral makes contact with many more motoneurones than has previously been suggested in fact with fifty to sixty rather than with about ten.
Aortic distensibility and arterial–ventricular coupling in early chronic kidney disease: a pattern resembling heart failure with preserved ejection fraction

Objectives: To examine arterial and left ventricular function and their interaction in patients with early-stage chronic kidney disease (CKD). Design and setting: Cross-sectional observational study in a university teaching hospital. Patients: 117 patients with stage 2 (60–89 ml/min/1.73 m2) or stage 3 (30–59 ml/min/1.73 m2) non-diabetic CKD, without overt cardiovascular disease were compared with 40 controls. Interventions: Aortic distensibility and left ventricular mass were assessed using cardiac magnetic resonance imaging. Systolic and diastolic ventricular function and arterial–ventricular elastance (stiffness) were assessed by transthoracic echocardiography. Main outcome measures: Arterial stiffness as measured by aortic distensibility and arterial elastance. Left ventricular mass, left ventricular systolic and diastolic function, including end-diastolic and end-systolic elastance and their relationship with arterial elastance. Results: Compared with controls, patients with CKD 2 and CKD 3 had reduced aortic distensibility (4.12 (1.3) vs 2.94 (1.8) vs 2.18 (1.8)×10–3 mm Hg, p<0.01), increased arterial elastance (1.4 (1.3) vs 1.65 (0.40) vs 1.74 0.48) mm Hg, p<0.05) and increased end-systolic (1.88 (0.48) vs 2.43 (0.83) vs 2.42(0.78) mm Hg/ml, p<0.05) and end diastolic elastances (0.07 (0.04) vs 0.11 (0.04) vs 0.12 (0.04, p<0.01). Aortic distensibility was positively correlated with estimated glomerular filtration rate (r = 0.349, p<0.01) and indices of elastance were inversely correlated (r = 0.284, p<0.05). Systolic function was not impaired in patients with early CKD compared with controls but diastolic filling velocities (Em) were reduced (8.1 (0.9) vs 7.9 (0.6) vs 7.5 (0.7) cm/s, p<0.01) while mean left atrial pressure (E/Em) was increased (5.6 (1.1), vs 7.4 (1.8) vs 8.0 (2.4), p<0.01) and end-diastolic elastance was increased. Conclusions: Early-stage CKD is characterised by reduced aortic distensibility and increases in arterial, ventricular systolic and diastolic stiffness; arterial–ventricular coupling is preserved. This pattern of pathophysiological abnormalities resembles that seen in heart failure with preserved ejection fraction and may account for the high levels of cardiovascular morbidity and mortality in patients at all stages of CKD. Trial Registration Number: NCT00291720
Unexpectedly high strain diversity of Mycobacterium tuberculosis in a high-incidence community.

OBJECTIVE To characterise Mycobacterium tuberculosis strains present in a community experiencing an epidemic, in order to establish whether a high rate of transmission results in low strain diversity. DESIGN Sputum specimens collected for 18 months; IS6110-based DNA fingerprinting. SETTING The communities of Ravensmead and Uitsig, Cape Town, South Africa. PARTICIPANTS Three hundred and thirty-four pulmonary tuberculosis patients attending the Local Authority Health Care Clinic. MAIN OUTCOME MEASURE DNA fingerprinting. RESULTS A total of 334 M. tuberculosis isolates were characterised by IS6110-based DNA fingerprinting; 209 strains were identified, 199 having 5 or more insertions. Forty of these strains were present in 2 or more patients (clustering--126 patients in total), which indicates a recent transmission rate of 30%. The 163 unique strains suggest reactivation of latent infections. Computer analysis showed a high degree of strain diversity, and a common progenitor could only be linked to 33% of the strains. Clustering was shown in 50% of drug-resistant isolates. CONCLUSIONS The low rate of transmission (30%) and the high degree of strain diversity (209 strains) was unexpected and unexplained, given the high burden of disease in this community. The clustering of drug-resistant strains suggests that transmission, rather than lack of compliance, drives the spread of antibiotic resistance in this community. Preliminary indications are that BCG vaccination, while having little effect on the incidence of tuberculosis in this community, may have altered the strain dynamics.