Miracle-dz/UniFAR-FTUs huggingface dataset:
Breathlessness during acute bronchoconstriction in asthma. Pathophysiologic mechanisms.

The purpose of this study was to examine potential contributing factors to breathlessness during bronchoconstriction, in particular, to evaluate the role of lung hyperinflation. We also wished to elucidate qualitative aspects of the unpleasant sensory experience and to identify factors that contribute to intersubject variability in subjective and objective assessments of airflow obstruction. We studied sensory-mechanical interrelationships during and after induced bronchoconstriction in 21 subjects with mild stable asthma. Breathlessness (Borg scale), spirometry, and inspiratory capacity (IC) were measured after each dose during methacholine bronchoprovocation to a maximal change (delta) in FEV1 of 50%. Breathing pattern, specific airway resistance (SRaw), plethysmographic thoracic gas volume, and maximal inspiratory mouth pressure (MIP) were recorded at baseline, at maximal response, and at full symptom recovery. End-expiratory lung volume (EELV) was derived from IC. Borg increased from 0.4 +/- 0.1 (very, very slight) at baseline to 5.0 +/- 0.5 (severe) at maximal bronchoconstriction (mean +/- SEM, p < 0.001). FEV1 fell significantly (p < 0.001) to 48% predicted at maximal response. Of the 21 subjects, 19 reported increased inspiratory rather than expiratory difficulty and predominantly described sensations of reduced inspiratory capacity and unrewarded inspiratory effort. Stepwise multiple regression analysis using delta Borg (outcome variable) versus changes in spirometry, SRaw, IC, and breathing pattern components, selected delta IC as the principal contributing factor: delta Borg = 0.09 (delta IC, %fall); n = 193, r = 0.86, p < 0.001. delta IC continued to contribute significantly (p < 0.001) to the variance in Borg ratings after accounting for delta FEV1, and it was the strongest predictor of symptom recovery (p < 0.05). (ABSTRACT TRUNCATED AT 250 WORDS)
Hospital Competition, Quality, and Expenditures in the U.S. Medicare Population

Theoretical models of competition with fixed prices suggest that hospitals should compete by increasing quality of care for diseases with the greatest profitability and demand elasticity. Most empirical evidence regarding hospital competition is limited to heart attacks, which in the U.S. generate positive profit margins but exhibit very low demand elasticity – ambulances usually take patients to the closest (or affiliated) hospital. In this paper, we derive a theoretically appropriate measure of market concentration in a fixed-price model, and use differential travel-time to hospitals in each of the 306 U.S. regional hospital markets to instrument for market concentration. We then estimate the model using risk-adjusted Medicare data for several different population cohorts: heart attacks (low demand elasticity), hip and knee replacements (high demand elasticity) and dementia patients (low demand elasticity, low or negative profitability). First, we find little correlation within hospitals across quality measures. And second, while we replicate the standard result that greater competition leads to higher quality in some (but not all) measures of heart attack quality, we find essentially no association between competition and quality for what should be the most competitive markets – elective hip and knee replacements. Consistent with the model, competition is associated with lower quality care among dementia patients, suggesting that competition could induce hospitals to discourage unprofitable patients.
Severe Acute Respiratory Syndrome (SARS) in a Liver Transplant Recipient and Guidelines for Donor SARS Screening

Severe acute respiratory syndrome (SARS) is a recently described infectious entity with salient features of fever, headache and malaise, with rapid progression to pneumonitis. The etiology of SARS is likely a novel coronavirus. During the winter of 2003, an outbreak of SARS involving several hospitals occurred in Toronto, Canada. We describe a patient post liver transplant who contracted SARS and died during the outbreak, with subsequent infection of family and several health‐care workers. A novel coronavirus was detected in respiratory specimens by PCR. Due to the potential severity of SARS in transplant recipients and the large number of cases of SARS in the community, in order to avoid transmission of SARS from a donor, we developed guidelines for SARS screening of organ donors. A screening tool based on potential hospital SARS exposure, clinical symptoms, and epidemiological exposure was used to stratify donors as high, intermediate or low risk for SARS. As SARS spreads throughout the world, it may become an increasingly significant problem for transplant patients and programs.
Activation of Mas Oncogene-Related G Protein–Coupled Receptors Inhibits Neurochemical Alterations in the Spinal Dorsal Horn and Dorsal Root Ganglia Associated with Inflammatory Pain in Rats

Mas oncogene-related G protein–coupled receptor C (MrgC) is unequally expressed in sensory ganglia and has been shown to modulate pathologic pain. This study investigated the mechanism underlying the effect of MrgC receptors on inflammatory pain. Intrathecal administration of the selective MrgC receptor agonist bovine adrenal medulla 8-22 (BAM8-22) (30 nmol) inhibited complete Freund’s adjuvant–evoked hyperalgesia. This was associated with the inhibition of protein kinase C-γ and phosphorylated extracellular signal-regulated protein kinase in the spinal cord and/or dorsal root ganglia (DRG). The complete Freund’s adjuvant injection in the hindpaw induced an increase in Gq, but not Gi and Gs, protein in the spinal dorsal horn. This increase was inhibited by the intrathecal administration of BAM8-22. The exposure of DRG cultures to bradykinin (10 μM) and prostaglandin E2 (1 μM) increased the expression of calcitonin gene-related peptide (CGRP) and neuronal nitric oxide synthase in small- and medium-sized neurons as well as the levels of CGRP, aspartate, and glutamate in the cultured medium. The bradykinin/prostaglandin E2–induced alterations were absent in the presence of BAM8-22 (10 nM). These results suggest that the activation of MrgC receptors can modulate the increase in the expression of CGRP and neuronal nitric oxide synthase as well as the release of CGRP and excitatory amino acids in DRG associated with inflammatory pain. This modulation results in the inhibition of pain hypersensitivity by suppressing the expression of Gq protein and protein kinase C-γ and extracellular signal-regulated protein kinase signaling pathways in the spinal cord and/or DRG. The present study suggests that MrgC receptors may be a novel target for relieving inflammatory pain.
Error bounds of optimization algorithms for semi-Markov decision processes

Cao's work shows that, by defining an α-dependent equivalent infinitesimal generator A α, a semi-Markov decision process (SMDP) with both average- and discounted-cost criteria can be treated as an α-equivalent Markov decision process (MDP), and the performance potential theory can also be developed for SMDPs. In this work, we focus on establishing error bounds for potential and A α-based iterative optimization methods. First, we introduce an α-uniformized Markov chain (UMC) for a SMDP via A α and a uniformized parameter, and show their relations. Especially, we obtain that their performance potentials, as solutions of corresponding Poisson equations, are proportional, so that the studies of a SMDP and the α-UMC based on potentials are unified. Using these relations, we derive the error bounds for a potential-based policy-iteration algorithm and a value-iteration algorithm, respectively, when there exist various calculation errors. The obtained results can be applied directly to the special models, i.e., continuous-time MDPs and Markov chains, and can be extended to some simulation-based optimization methods such as reinforcement learning and neuro-dynamic programming, where estimation errors or approximation errors are common cases. Finally, we give an application example on the look-ahead control of a conveyor-serviced production station (CSPS), and show the corresponding error bounds.
Molecular Basis of Rifampin and Isoniazid Resistance in Mycobacterium bovis Strains Isolated in Sardinia, Italy

ABSTRACT Fourteen of 22 (68%) Mycobacterium bovis strains isolated from cattle in Sardinia were found to be resistant to rifampin and isoniazid. Analysis of the rpoB and the katG, oxyR-ahpC, and inhA gene regions of these strains was performed in order to investigate the molecular basis of rifampin and isoniazid resistance, respectively. The most frequent mutation, encountered in 6 of 10 strains (60%), was in the rpoBgene; it occurred, at codon position 521 and resulted in leucine changed to proline. This suggests that codon 521 may be important for the development of rifampin resistance in M. bovis. Resistance to isoniazid is associated in Mycobacterium tuberculosis with a variety of mutations affecting one or more genes. Our results confirm the difficulty of interpreting the sequence variations observed in clinical strains of M. bovis. M. bovis strains isolated from the same geographic area showed similar mutations within the genes responsible for rifampin and isoniazid resistance. Our results represent the first study to elucidate the molecular genetic basis of drug resistance in M. bovis isolated from cattle.
Human Spatial Navigation via a Visuo-Tactile Sensory Substitution System

Spatial navigation within a real 3-D maze was investigated to study space perception on the sole basis of tactile information transmitted by means of a ‘tactile vision substitution system' (TVSS) allowing the conversion of optical images—collected by a micro camera—into ‘tactile images’ via a matrix in contact with the skin. The development of such a device is based on concepts of cerebral and functional plasticity, enabling subjective reproduction of visual images from tactile data processing. Blindfolded sighted subjects had to remotely control the movements of a robot on which the TVSS camera was mounted. Once familiarised with the cues in the maze, the subjects were given two exploration sessions. Performance was analysed according to an objective point of view (exploration time, discrimination capacity), as well as a subjective one (speech). The task was successfully carried out from the very first session. As the subjects took a different path during each navigation, a gradual improvement in performance (discrimination and exploration time) was noted, generating a phenomenon of learning. Moreover, subjective analysis revealed an evolution of the spatialisation process towards distal attribution. Finally, some emotional expressions seemed to reflect the genesis of ‘qualia’ (emotional qualities of stimulation).
Basic Residues within the Ebolavirus VP35 Protein Are Required for Its Viral Polymerase Cofactor Function

ABSTRACT The ebolavirus (EBOV) VP35 protein binds to double-stranded RNA (dsRNA), inhibits host alpha/beta interferon (IFN-α/β) production, and is an essential component of the viral polymerase complex. Structural studies of the VP35 C-terminal IFN inhibitory domain (IID) identified specific structural features, including a central basic patch and a hydrophobic pocket, that are important for dsRNA binding and IFN inhibition. Several other conserved basic residues bordering the central basic patch and a separate cluster of basic residues, called the first basic patch, were also identified. Functional analysis of alanine substitution mutants indicates that basic residues outside the central basic patch are not required for dsRNA binding or for IFN inhibition. However, minigenome assays, which assess viral RNA polymerase complex function, identified these other basic residues to be critical for viral RNA synthesis. Of these, a subset located within the first basic patch is important for VP35-nucleoprotein (NP) interaction, as evidenced by the inability of alanine substitution mutants to coimmunoprecipitate with NP. Therefore, first basic patch residues are likely critical for replication complex formation through interactions with NP. Coimmunoprecipitation studies further demonstrate that the VP35 IID is sufficient to interact with NP and that dsRNA can modulate VP35 IID interactions with NP. Other basic residue mutations that disrupt the VP35 polymerase cofactor function do not affect interaction with NP or with the amino terminus of the viral polymerase. Collectively, these results highlight the importance of conserved basic residues from the EBOV VP35 C-terminal IID and validate the VP35 IID as a potential therapeutic target.
Considerations for Design and Use of Container Challenge Sets for Qualification and Validation of Visible Particulate Inspection

The major compendia require sterile injectable and ophthalmic drugs, to be prepared in a manner that is designed to exclude particulate matter. This requirement is satisfied by testing for subvisual particles in the laboratory and 100% inspection of all containers for the presence of visible particles. Inspection for visible particles is performed in the operations area using one of three methods. Manual inspection is based on human visual acuity, the ability of the inspector to discern between conforming and nonconforming containers, and the ability to remove nonconforming units. Semi-automated inspection is a variation of manual inspection, in which a roller conveyor handles and presents the containers to the human inspector. Fully automated inspection systems perform handling, inspection, and rejection of defective containers. All inspection methods must meet the compendial requirement for sterile drug product to be “essentially free” of visible particulates. Given the random occurrence of particles within the batch, visual detection of a particle in an individual container is probabilistic. The probability of detection for a specific particle is affected by many variables that include product attributes, container size and shape, particle composition and size, and inspection capability. The challenge set is a useful tool to assess the particle detection in a product, and it may also be used to evaluate detection of container/closure defects. While the importance of a well-designed challenge set is not always recognized or understood, it serves as the cornerstone for qualification and/or validation of all inspection methods. This article is intended to provide useful information for the design, composition, and use of container challenge sets for particulate inspection studies. LAY ABSTRACT: Regulations require drug products intended for injection or ophthalmic use to be sterile and free of particles that could harm the patient. This requirement is meet by 100% inspection of every drug container in the lot and the removal of any defective unit before it is released for patient use. Great progress has been made through the creation of a harmonized method for the detection of small particles in drug product and universal recognition of container defects. Differing opinions concerning the conduct of large particle inspection have hindered the creation of a harmonized method. The absence of a standard method has created confusion that must be resolved for acceptance of drug products in the global marketplace. While the importance of a well-designed test set for qualification of these methods is overlooked or misunderstood, it can serve as the cornerstone for qualification of all inspection methods. This article is intended to provide valuable information for test sets used qualify inspection systems. The proper design and use of these test sets will provide clarity for inspection qualification, which can be applied to the inspection of commercial product.
A review of the thoracic splanchnic nerves and celiac ganglia

Anatomical variation of the thoracic splanchnic nerves is as diverse as any structure in the body. Thoracic splanchnic nerves are derived from medial branches of the lower seven thoracic sympathetic ganglia, with the greater splanchnic nerve comprising the more cranial contributions, the lesser the middle branches, and the least splanchnic nerve usually T11 and/or T12. Much of the early anatomical research of the thoracic splanchnic nerves revolved around elucidating the nerve root level contributing to each of these nerves. The celiac plexus is a major interchange for autonomic fibers, receiving many of the thoracic splanchnic nerve fibers as they course toward the organs of the abdomen. The location of the celiac ganglia are usually described in relation to surrounding structures, and also show variation in size and general morphology. Clinically, the thoracic splanchnic nerves and celiac ganglia play a major role in pain management for upper abdominal disorders, particularly chronic pancreatitis and pancreatic cancer. Splanchnicectomy has been a treatment option since Mallet‐Guy became a major proponent of the procedure in the 1940s. Splanchnic nerve dissection and thermocoagulation are two common derivatives of splanchnicectomy that are commonly used today. Celiac plexus block is also a treatment option to compliment splanchnicectomy in pain management. Endoscopic ultrasonography (EUS)‐guided celiac injection and percutaneous methods of celiac plexus block have been heavily studied and are two important methods used today. For both splanchnicectomies and celiac plexus block, the innovation of ultrasonographic imaging technology has improved efficacy and accuracy of these procedures and continues to make pain management for these diseases more successful. Clin. Anat. 23:512–522, 2010. © 2010 Wiley‐Liss, Inc.
Cortical and subcortical gray matter abnormalities in schizophrenia determined through structural magnetic resonance imaging with optimized volumetric voxel-based morphometry.

OBJECTIVE Structural neuroimaging studies have suggested an association between schizophrenia and abnormalities in brain morphology such as ventricular enlargement and differences in gray matter distribution. Less consistently reported are findings of regional abnormalities such as selective differences in thalamic volume. The authors applied an unbiased technique to test for differences in cerebral morphometry between patients with schizophrenia and matched comparison subjects. METHOD T(1)-weighted images from 20 schizophrenic patients and matched comparison subjects were processed by using optimized automated voxel-based morphometry within multiple linear regression analyses. RESULTS Global differences in gray matter volume were seen between the schizophrenic and comparison subjects, with selective regional gray matter differences noted in the mediodorsal thalamus and across cortical regions, including the ventral and medial prefrontal cortices. Within the schizophrenic subjects, a relationship was observed between gray matter volume loss in the medial prefrontal cortex and a positive family history of schizophrenia. There was no significant difference between patients and comparison subjects in rates of proportional gray matter reduction with age. CONCLUSIONS These observations confirm an association between thalamocortical morphometric abnormalities and schizophrenia, consistent with theoretical models of primary pathoetiological dysfunction in filtering, integration, and information transfer processes in patients with schizophrenia.
Influence of weather, rank, and home advantage on football outcomes in the Gulf region.

PURPOSE The objective of this study was to investigate the effects of weather, rank, and home advantage on international football match results and scores in the Gulf Cooperation Council (GCC) region. METHODS Football matches (n = 2008) in six GCC countries were analyzed. To determine the weather influence on the likelihood of favorable outcome and goal difference, generalized linear model with a logit link function and multiple regression analysis were performed. RESULTS In the GCC region, home teams tend to have greater likelihood of a favorable outcome (P < 0.001) and higher goal difference (P < 0.001). Temperature difference was identified as a significant explanatory variable when used independently (P < 0.001) or after adjustment for home advantage and team ranking (P < 0.001). The likelihood of favorable outcome for GCC teams increases by 3% for every 1-unit increase in temperature difference. After inclusion of interaction with opposition, this advantage remains significant only when playing against non-GCC opponents. While home advantage increased the odds of favorable outcome (P < 0.001) and goal difference (P < 0.001) after inclusion of interaction term, the likelihood of favorable outcome for a GCC team decreased (P < 0.001) when playing against a stronger opponent. Finally, the temperature and wet bulb globe temperature approximation were found as better indicators of the effect of environmental conditions than absolute and relative humidity or heat index on match outcomes. CONCLUSIONS In GCC region, higher temperature increased the likelihood of a favorable outcome when playing against non-GCC teams. However, international ranking should be considered because an opponent with a higher rank reduced, but did not eliminate, the likelihood of a favorable outcome.
Is the Predisposition to Neuroleptic Malignant Syndrome Genetically Transmitted?

A Japanese family consisting of a mother and her two daughters, all experienced NMS on therapeutic or subtherapeutic doses of neuroleptics. The mother and the elder daughter had past histories of severe neuroleptic-induced extrapyramidal symptoms. The predisposition to this syndrome may be genetically transmitted. We suggest that neuroleptic treatment should be introduced with extreme caution to a patient with a family history of NMS.
PTPN11 (Shp2) Mutations in LEOPARD Syndrome Have Dominant Negative, Not Activating, Effects*

Multiple lentigines/LEOPARD syndrome (LS) is a rare, autosomal dominant disorder characterized by Lentigines, Electrocardiogram abnormalities, Ocular hypertelorism, Pulmonic valvular stenosis, Abnormalities of genitalia, Retardation of growth, and Deafness. Like the more common Noonan syndrome (NS), LS is caused by germ line missense mutations in PTPN11, encoding the protein-tyrosine phosphatase Shp2. Enzymologic, structural, cell biological, and mouse genetic studies indicate that NS is caused by gain-of-function PTPN11 mutations. Because NS and LS share several features, LS has been viewed as an NS variant. We examined a panel of LS mutants, including the two most common alleles. Surprisingly, we found that in marked contrast to NS, LS mutants are catalytically defective and act as dominant negative mutations that interfere with growth factor/Erk-mitogen-activated protein kinasemediated signaling. Molecular modeling and biochemical studies suggest that LS mutations contort the Shp2 catalytic domain and result in open, inactive forms of Shp2. Our results establish that the pathogenesis of LS and NS is distinct and suggest that these disorders should be distinguished by mutational analysis rather than clinical presentation.
Twenty-four-hour pattern of circulation by radiotelemetry in the unrestrained dog.

Eight dogs with indwelling transducers for continuous radiotelemetry of the hemodynamic function were acclimatized in an unisolated room under 12:12 LD photoperiods, in phase with the solar day cycle, and constant temperature (20 +/- 1 degrees C). Light was turned on at 0600 and off at 1800. Mean aortic blood flow (ABF), mean aortic blood pressure (ABP), heart rate (HR), respiratory rate (RR), and cardiac work (CW) were maximal at about 1800 and minimal at time 0600. Total peripheral resistance (TPR) was highest and stroke volume (SV) lowest at about 1200. The 24-h mean was for HR 77 beats/min, SV 28 ml/beat, RR 11 breaths/min, ABF 177 ml/min per kg body wt, ABP 102 Torr, TPR 3,960 dyn . s . cm-5, and CW 218 Torr . 1/min. The range of amplitude fluctuations for daytime means was about 6% for ABP and SV and 11-17% for all others. It is suggested that the homeostatic balance and timing of circulation is circadian time dependent.