Miracle-dz/UniFAR-FTUs huggingface dataset:
The steady-state pharmacokinetics of nevirapine during once daily and twice daily dosing in HIV-1-infected individuals

ObjectiveTo investigate and to compare the steady-state plasma pharmacokinetics of nevirapine in a dosing regimen of 400 mg once daily versus 200 mg twice daily in HIV-1-infected individuals. DesignOpen-label, randomized, cross-over study. MethodsTwenty HIV-1-infected individuals who already used nevirapine as part of their antiretroviral regimen were randomized to continue their current regimen (200 mg twice daily) or to switch to the alternate regimen (400 mg once daily). The steady-state plasma pharmacokinetics of nevirapine were assessed after 2 weeks during a 24-h period. Subsequently, patients were switched to the alternate regimen and the pharmacokinetics of nevirapine were assessed again after 2 weeks. Non-compartmental methods were used to calculate the area under the plasma concentration versus time curve (AUC[24h]), and the maximal (Cmax) and minimal plasma concentration (Cmin), the time to Cmax (tmax), the plasma elimination half-life (t1/2), the apparent oral clearance (Cl/ F) and the apparent volume of distribution (V/ F). Differences in these pharmacokinetic parameters for the two dosing regimens were tested using ANOVA. ResultsThe exposure to nevirapine, as measured by the AUC[24h], was not significantly different between the 400 mg once daily and 200 mg twice daily dosing regimen (P = 0.60). Furthermore, the values for tmax, t1/2Cl/ F and V/ F were not significantly different between the two dosing regimens (P ⩾ 0.08). However, Cmax and Cmin were higher and lower, respectively, when nevirapine was used in the once daily regimen as compared with the twice daily regimen. The median values for Cmax and Cmin as measured for the once daily and twice daily regimens were 6.69 and 5.74 μg/ml, respectively (P = 0.03), and 2.88 and 3.73 μg/ml, respectively (P < 0.01). ConclusionThese data show that the daily exposure to nevirapine, as measured by the plasma AUC[24h], is not different between a 400 mg once daily and a 200 mg twice daily dosing regimen. However, Cmax and Cmin are higher and lower, respectively, for the once daily regimen as compared with the twice daily regimen. The clinical implications of these differences remain to be established.
Modeling impacts of farming management alternatives on CO2, CH4, and N2O emissions: A case study for water management of rice agriculture of China

Since the early 1980s, water management of rice paddies in China has changed substantially, with midseason drainage gradually replacing continuous flooding. This has provided an opportunity to estimate how a management alternative impacts greenhouse gas emissions at a large regional scale. We integrated a process‐based model, DNDC, with a GIS database of paddy area, soil properties, and management factors. We simulated soil carbon sequestration (or net CO2 emission) and CH4 and N2O emissions from China's rice paddies (30 million ha), based on 1990 climate and management conditions, with two water management scenarios: continuous flooding and midseason drainage. The results indicated that this change in water management has reduced aggregate CH4 emissions about 40%, or 5 Tg CH4 yr−1, roughly 5–10% of total global methane emissions from rice paddies. The mitigating effect of midseason drainage on CH4 flux was highly uneven across the country; the highest flux reductions (>200 kg CH4‐C ha−1 yr−1) were in Hainan, Sichuan, Hubei, and Guangdong provinces, with warmer weather and multiple‐cropping rice systems. The smallest flux reductions (<25 kg CH4‐C ha−1 yr−1) occurred in Tianjin, Hebei, Ningxia, Liaoning, and Gansu Provinces, with relatively cool weather and single cropping systems. Shifting water management from continuous flooding to midseason drainage increased N2O emissions from Chinese rice paddies by 0.15 Tg N yr−1 (∼50% increase). This offset a large fraction of the greenhouse gas radiative forcing benefit gained by the decrease in CH4 emissions. Midseason drainage‐induced N2O fluxes were high (>8.0 kg N/ha) in Jilin, Liaoning, Heilongjiang, and Xinjiang provinces, where the paddy soils contained relatively high organic matter. Shifting water management from continuous flooding to midseason drainage reduced total net CO2 emissions by 0.65 Tg CO2‐C yr−1, which made a relatively small contribution to the net climate impact due to the low radiative potential of CO2. The change in water management had very different effects on net greenhouse gas mitigation when implemented across climatic zones, soil types, or cropping systems. Maximum CH4 reductions and minimum N2O increases were obtained when the mid‐season draining was applied to rice paddies with warm weather, high soil clay content, and low soil organic matter content, for example, Sichuan, Hubei, Hunan, Guangdong, Guangxi, Anhui, and Jiangsu provinces, which have 60% of China's rice paddies and produce 65% of China's rice harvest.
Foramen magnum as a tool for sexual dimorphism: A cone beam computed tomography study

Background and Objectives: (1) To evaluate dimensions of the foramen magnum (FM) among males and females and to establish its role in sexual dimorphism using cone beam computed tomography (CBCT). (2) To evaluate sagittal diameter, transverse diameter, area, and circumference of FM among males and females. Materials and Methods: Two hundred and eighty CBCT scans (140 males and 140 females; age range, 20-80 years) were selected for this study. The sagittal diameter, transverse diameter, area, and circumference of FM were measured, and data were subjected to discriminant analysis for the evaluation of sexual dimorphism. Results: The area of FM was the best discriminant parameter which is used to study the sexual dimorphism with an overall accuracy of 72%. Interpretation and Conclusions: It can be concluded that the reconstructed CBCT image provides valuable measurements for the FM and could be used for sexing even when other methods are inconclusive.
Predictors of outcome in hospitalized patients with severe hyponatremia.

UNLABELLED Severe hyponatremia is associated with increased morbidity and mortality. Clinicians treating patients with severe hyponatremia are often torn between a desire to promptly raise serum sodium concentration to a "safe range," and at the same time, to avoid excessively rapid correction of hyponatremia. The aim of this study was to assess the prevalence of severe hyponatremia in hospitalized patients, the etiologic factors involved, as well as treatment and outcome of the patients using a retrospective case series. METHODS Retrospective study of 168 patients with severe hyponatremia (< 115mmol/L) seen at Grady Memorial Hospital, a tertiary teaching hospital, in Atlanta, Georgia, from 1997-2001. The main outcome measures of interest were death during admission or occurrence of neurologic symptoms before, during or after therapy. RESULTS One hundred sixty-eight patients met the inclusion criteria out of a total of 5994 patients with hyponatremia treated at our hospital over the study period. Eighty-nine patients (52.9%) were symptomatic. The mean absolute serum sodium at 48-hours of therapy was 120.02 +/- 8.31 mmol/L. Respiratory failure and/or hypoxia was present in 28 patients (16.7%); sepsis was documented in 16 patients (9.5%). Mortality rate was high, 34 patients died (20.2%). On multivariate analysis factors with strong association with mortality of patients with severe hyponatremia were hypoxia, presence of neurologic symptoms, slow correction rates and a diagnosis of sepsis. CONCLUSIONS The mortality associated with severe hyponatremia remains high. Sepsis, respiratory failure and the presence of symptoms predict poor outcome in hospitalized patients with severe hyponatremia. More aggressive therapy with 3% saline may improve outcome in symptomatic patients. Our data suggest that a slow rate of correction in severe hyponatremia is associated with higher mortality than rapid correction, at least in the short-term.
The CAREGENE study: polymorphisms of the beta1-adrenoceptor gene and aerobic power in coronary artery disease.

AIMS The heritability of aerobic power and of the response to physical training has been shown in healthy subjects. beta(1)-Adrenergic receptor (beta(1)AR) function affects exercise performance. This study aims to investigate whether the Ser49Gly and Gly389Arg polymorphisms of the beta(1)AR gene or their haplotypes are associated with aerobic power or its response to physical training in coronary artery disease (CAD). METHODS AND RESULTS Nine hundred and thirty-five biologically unrelated Caucasian patients with CAD who had exercised until exhaustion during graded bicycle testing at baseline and after completion of 3 months of exercise training from 1990 to 2001 (n = 1095) were eligible for inclusion in the CAREGENE (CArdiac REhabilitation and GENetics of Exercise performance) study. Polymorphisms were detected using the invader assay (Third Wave Technologiestrade mark, Madison, Wisconsin, USA). Patients with the Gly49Gly genotype had significantly higher covariate-adjusted aerobic power at baseline than those with Ser49Ser and Ser49Gly (P < 0.05). Adjusted aerobic power at baseline was highest in the Ser49-Gly389/Gly49-Gly389 and Gly49-Arg389/Gly49-Arg389 haplotype combinations. Aerobic power increased significantly (P < 0.001) with physical training. There was no association with the effect of physical training. CONCLUSION Ser49Gly and haplotype combinations of Ser49Gly and Gly389Arg of the beta(1)AR gene are associated with aerobic power, but not with the response to physical training in patients with CAD included in the CAREGENE study.
State estimation for linear impulsive systems

In this paper, we treat the fundamental problem of state estimation for a class of linear impulsive systems with time-driven impulsive effects. We show that a strong observability property enables an impulsive observer to be constructed that yields uniformly exponentially stable estimation error dynamics. This approach accommodates impulsive systems with arbitrarily-spaced impulse times and singular state transition matrices in a manner reminiscent of well-known results for time-varying discrete-time linear systems. As an example, an observer is constructed for an impulsive system that produces general cubic spline signals
Introduction to the treatment of lung cancer.

Lung cancer represents the leading cause of cancer mortality worldwide. Its incidence has declined in men but is increasing in women, assuring that this largely preventable disease will continue to affect millions. In small cell lung cancer, the advent of chemotherapy in the 1970s and continued refinements in the 1980s yielded improved median survivals in patients with both limited disease and extensive disease and improved long-term survival in limited-disease patients. Reinduction chemotherapy was shown in the 1980s to improve survival in patients who had achieved a complete remission to initial chemotherapy, and a consensus subsequently developed regarding standard induction chemotherapy for patients with small cell lung cancer. The prognosis for patients with small cell lung cancer depends largely on delivering the optimal combination chemotherapy to achieve early, maximal cell kill with manageable toxicity. Future challenges include comparing newer combinations and novel schedules of administration with "standard" chemotherapy, optimizing the use of complementary treatment modalities, and refining prognostic factors to better define treatment and improve outcome. In patients with non-small cell lung cancer, single-modality treatment has been compared with combined-modality therapy in numerous randomized trials, with consistent survival benefits accrued by patients in combined-modality treatment arms. The recent availability of novel cytotoxic and cytostatic agents has prompted additional comparisons of new combination-chemotherapy regimens, with or without other treatment modalities, in patients with lung cancer. Questions for the future include defining the most effective chemotherapy to eradicate distant metastases and understanding which modalities offer superior local control.
Infantile Hydrocephalus–the Impact of Enhanced Preterm Survival

ABSTRACT. The epidemiology of infantile hydrocephalus (IH) in the birth years 1983‐86 was investigated in the south‐western health care region of Sweden. The study was made as a continuation of a previous one which had shown a significant increase in the prevalence of IH in 1967‐82. That rise was entirely referable to the relatively larger number of preterm IH infants born in 1979‐82 and was considered to be due to the enhanced survival, especially of very preterm infants. The present series comprised 57 liveborn IH infants‐27 preterms and 30 born at term. The livebirth prevalence of IH was 0.64 per 1000, 0.30 for preterm and 0.34 for fullterm infants. The high prevalence of preterm IH infants in 1979‐82 had persisted, but had not increased further. This might indicate an improved outcome in preterm survivors in the period 1983‐86, as the survival rate had continued to increase. The striking predominance of a perinatal aetiology of IH in very preterm infants could be confirmed: 90 % had had intraventricular haemorrhages verified by ultrasound in the postpartum period. The outcome in very preterm surviving infants with IH was still alarmingly poor: 78% had cerebral palsy, 72 % mental deficiency, and 56 % epilepsy.
Weight from birth to 53 years: a longitudinal study of the influence on clinical hand osteoarthritis.

OBJECTIVE To determine the influence of body weight throughout the life course on the development of clinical hand osteoarthritis (OA). METHODS A British national survey was used to perform a prospective cohort study of 1,467 men and 1,519 women born in 1946. Weight was measured at birth and at subsequent followup visits through childhood and adulthood. The main outcome measure was the odds ratio for the presence of hand OA at the age of 53 years. RESULTS Two hundred eighty men (19%) and 458 women (30%) had OA in at least 1 hand joint. Hand OA was significantly associated with increased weight at ages 26 years, 43 years, and 53 years and with decreased weight at birth in men. Birth weight and adult weight showed independent effects, such that men with the highest risk for OA represented those who had been heaviest at age 53 years and lightest at birth. These findings were not explained by grip strength. There was no significant relationship between weight and hand OA in women. CONCLUSION The results of this study show that increased adult weight is associated with, and may precede, development of hand OA in men. An association between hand OA and weight was not observed in women. The relationship between hand OA and decreased birth weight is a new finding and may reflect the persisting influence of prenatal environmental factors on adult joint structure and function.
Admittance spectroscopy of interface states in polymer MIS devices

We have measured the admittance of metal-insulator-semiconductor (MIS) structures based on the p-type semiconducting polymer poly(3-hexylthiophene) with polyimide or polysilsequioxane insulating layers. In both cases, evidence is presented for the presence of fast and slow hole trapping interface states at the semiconductor-insulator interface. Evidence from photocapacitance measurements is also presented which suggests also the presence of electron-trapping interface states.
In vivo determination of intra‐myocellular lipids in human muscle by means of localized 1H‐MR‐spectroscopy

Intra‐myocellular lipids (IMCL) are stored in droplets in the cytoplasm of muscle cells and are an energy storage form readily accessed during long‐term exercise. 1H‐MR spectroscopy methods are presented for noninvasive determination of IMCL in human muscle. This is based on (a) the separation of two resonances in the lipid‐CH2‐region, with the one assigned to IMCL being independent of muscle orientation relative to the magnetic field and (b) the fact that IMCL resonances scale along with signal amplitudes of metabolites in the muscle cell (e.g., creatine) when voxel size is increased, while lipid signals of bulk fat show a disproportionate growth. Inter‐individual and intra‐individual reproducibility studies indicate that the error of the method is about 6% and that IMCL levels differ significantly between identical muscles in different subjects, as well as intra‐individually when measured at 1 week intervals. IMCL determinations in a single subject before and after strenuous exercise indicate that lipid stores recover with a t1/2 of about 1 day.
Superficial vein thrombosis and recurrent venous thromboembolism: a pooled analysis of two observational studies

Summary. Background: The management strategies for symptomatic isolated superficial vein thrombosis (SVT) (without concomitant deep vein thrombosis [DVT] or pulmonary embolism [PE]) have yet to achieve widespread consensus. Concerns have been raised regarding the usefulness of prescribing anticoagulant treatments to all patients with isolated SVT. Determining the isolated SVT subgroups who have the highest risks of venous thromboembolism (VTE) recurrence (composite of DVT, PE, and new SVT) may facilitate the identification of patients who are likely to benefit from anticoagulant treatment.
Viral etiology of intussusception in Taiwanese childhood.

BACKGROUND Adenovirus infection and lymphoid hyperplasia have been associated with childhood intussusception. However, the extent of other viruses involved in this condition remains unclear. This prospective study investigates the relationship between some lymphotropic viruses and current childhood intussusception. METHODS Patients with intussusception encountered in a pediatric emergency department in a recent 3-year period were studied. Healthy infants and toddlers of comparable age served as controls. Throat and rectal viral cultures were performed in patients and controls. Viral antibodies against adenovirus, cytomegalovirus, human herpesvirus (HHV)-6, HHV-7 and Epstein-Barr virus (EBV) were tested in paired sera from the patients. Acute stage serum from each patient and mesenteric lymph nodes from patients requiring surgery were studied for the presence of adenovirus genome by PCR. RESULTS Twenty-seven of 61 (44.3%) intussusception patients, but only 2 of 52 (3.8%) healthy controls shed nonenteric adenovirus in throat and rectal specimens (P < 0.001). Of the 27 (74.1%) patients who shed adenovirus, 20 were older than 1 year old, whereas only 1 of 15 (6.7%) similarly aged patients in a previous study from the same area three decades ago did so (P = 0.001). Among 43 patients with available paired sera, acute primary viral infection was found in 17 (39.5%) by adenovirus, 4 (9.3%) by HHV-6, 5 (11.6%) by HHV-7, 2 (4.7%) by EBV and none by cytomegalovirus. Multiple viral infections occurred in 6 patients. Adenovirus genome was detected in 4 of 9 mesenteric lymph nodes and in only 3 of 60 (5%) acute phase sera. CONCLUSIONS Primary nonenteric adenovirus infection contributes to current childhood intussusception. Acute primary HHV-6, HHV-7 and EBV infections also play etiologic roles.
Kidney Regeneration and Stem Cells

The kidney has the capacity to recover from ischemic and toxic insults. Although there has been debate about the origin of cells that replace injured epithelial cells, it is now widely recognized that intrinsic surviving tubular cells are responsible for the repair. On the other hand, the cells, which have stem cell–like characteristics, have been isolated in the kidney using various methods, but it remains unknown if these stem cells actually exist in the adult kidney and if they are involved in kidney regeneration. This review will focus on the pathophysiology of kidney regeneration and the contribution of renal stem cells. We also discuss possible therapeutic applications to kidney disease. Anat Rec, 297:129–136. 2014. © 2013 Wiley Periodicals, Inc.
Prolonged Nonepileptic Twilight State with Convulsive Manifestations After Febrile Convulsions: A Clinical and Electroencephalographic Study

Summary: EEGs were obtained from 14 infants during behavior clinically diagnosed as prolonged febrile seizures. The clinical manifestations during EEG recordings resembled complex partial seizures (CPS) with convulsive manifestations, but the accompanying EEG waveforms were not epileptiform. Rather, two types of slow wave activity occurred: One was continuous diffuse delta (CDD) waves; the other was diffuse rhythmic theta (DRT) waves. I have termed these clinical states “nonepileptic twilight states with convulsive manifestations” (NETC). Because the CDD and DRT activity was similar to childhood arousal responses, I hypothesized that NETC might be a prolonged arousal state with increased muscle tone induced by a preceding febrile convulsion.
Altered skeletal muscle fiber composition and size precede whole-body insulin resistance in young men with low birth weight.

CONTEXT Low birth weight (LBW), a surrogate marker of an adverse fetal milieu, is linked to muscle insulin resistance, impaired insulin-stimulated glycolysis, and future risk of type 2 diabetes. Skeletal muscle mass, fiber composition, and capillary density are important determinants of muscle function and metabolism, and alterations have been implicated in the pathogenesis of insulin resistance. OBJECTIVE The aim of this study was to investigate whether an adverse fetal environment (LBW) induces permanent changes in skeletal muscle morphology, which may contribute to the dysmetabolic phenotype associated with LBW. DESIGN AND SUBJECTS Vastus lateralis muscle was obtained by percutaneous biopsy from 20 healthy 19-yr-old men with birth weights at 10th percentile or lower for gestational age (LBW) and 20 normal birth weight controls, matched for body fat, physical fitness, and whole-body glucose disposal. Myofibrillar ATPase staining was used to classify muscle fibers as type I, IIa, and IIx (formerly type IIb), and double immunostaining was performed to stain capillaries (LBW, n=8; normal birth weight, n=12). RESULTS LBW was associated with increased proportion of type IIx fibers (+66%; P=0.03), at the expense of decreased type IIa fibers (-22%; P=0.003). No significant change was observed in proportion of type I fibers (+16%; P=0.11). In addition, mean area of type IIa fibers was increased (+29%; P=0.01) and tended to be increased for type I fibers as well (+17%; P=0.08). Capillary density was not significantly different between groups. CONCLUSION Alterations in fiber composition and size may contribute to development of type 2 diabetes in individuals with LBW.