Miracle-dz/UniFAR-FTUs huggingface dataset:
Expression of the immunoglobulin superfamily neuroplastin adhesion molecules in adult and developing mouse cerebellum and their localisation to parasagittal stripes

Neuroplastin (np) 55 and 65 are immunoglobulin superfamily members that arise by alternative splicing of the same gene and have been implicated in long‐term activity‐dependent synaptic plasticity. Both biochemical and immunocytochemical data suggest that np55 is the predominant isoform (>95% of total neuroplastin) in cerebellum. Neuroplastin immunoreactivity is concentrated in the molecular layer and synaptic glomeruli in the granule cell layer. Expression in the molecular layer appears to be postsynaptic. First, neuroplastin is associated with Purkinje cell dendrites in two mouse granuloprival cerebellar mutants, disabled and cerebellar deficient folia. Second, in an acid sphingomyelinase knockout mouse with widespread protein trafficking defects, neuroplastin accumulates in the Purkinje cell somata. Finally, primary cerebellar cultures show neuroplastin expression in Purkinje cell dendrites and somata lacking normal histotypic organization and synaptic connections, and high‐magnification views indicate a preferential association with dendritic spines. In the molecular layer, differences in neuroplastin expression levels present as a parasagittal array of stripes that alternates with that revealed by the expression of another compartmentation antigen, zebrin II/aldolase c. Neuroplastin immunoreactivity is first detected weakly at postnatal day 3 (P3) in the anterior lobe vermis. By P5, parasagittal stripes are already apparent in the immature molecular layer. At this stage, punctate deposits are also localised at the perimeter of the Purkinje cell perikarya; these are no longer detected by P15. The data suggest a role for neuroplastins in the development and maintenance of normal synaptic connections in the cerebellum. J. Comp. Neurol. 462:286–301, 2003. © 2003 Wiley‐Liss, Inc.
Work related asthma. A causal analysis controlling the healthy worker effect

Objectives The healthy worker effect usually leads to underestimation of the association between occupational exposure and asthma. The role of irritants in work-related asthma is disputed. We estimated the effect of occupational exposure on asthma expression in a longitudinal study, using marginal structural modelling to control for the healthy worker effect. Methods Analyses included 1284 participants (17–79 years, 48% men) from the follow-up (2003–2007) of the French Epidemiological study on the Genetics and Environment of Asthma (case-control study). Age at asthma onset, periods with/without attacks over lifetime and occupational history were recorded retrospectively. Exposures to known asthmagens, irritants or low level of chemicals/allergens were evaluated through a job-exposure matrix. The job history was reconstructed into 5-year intervals. Results Thirty-one per cent of subjects had ever been exposed to occupational asthmagens. Among the 38% of subjects who had asthma (ever), presence of attacks was reported in 52% of all time periods. Using standard analyses, no association was observed between exposure to known asthmagens (OR (95% CI): 0.99 (0.72 to 1.36)) or to irritants/low level of chemicals/allergens (0.82 (0.56 to 1.20)) and asthma attacks. Using a marginal structural model, all associations increased with suggestive evidence for known asthmagens (1.26 (0.90 to 1.76)), and reaching statistical significance for irritants/low level of chemicals/allergens (1.56 (1.02 to 2.40)). Conclusions The healthy worker effect has an important impact in risk assessment in work-related asthma studies. Marginal structural models are useful to eliminate imbalances in exposure due to disease-driven selection. Results support the role of irritants in work-related asthma.
Sequential mergers under general symmetric product differentiation with four firms

This paper studies the types of sequential mergers that emerge and how they emerge when goods produced by firms in an industry are differentiated. In particular, we employ the most general differentiation setting with four firms by introducing a new parameter describing the highest degree of differentiation. We analyze how the degree of product differentiation affects the emergence of sequential mergers and find that when the value of this new parameter decreases, sequential mergers are more likely to emerge. Furthermore, we also provide welfare and numerical analyses to discuss the product differentiation ranges that would or would not lead to sequential mergers or no mergers in equilibrium. Consequently, policymakers can use this new parameter as a rule-of-thumb parameter in predicting the future merger structure.
Postural proprioceptive reflexes in standing human subjects: bandwidth of response and transmission characteristics.

1. This study investigated the reflex control of postural sway during human bipedal stance. The experiments were designed to: (i) find evidence for the operation of 'stretch reflex' pathways during quiet stance, (ii) determine the bandwidth of the reflex response, (iii) describe the reflex transmission characteristics in standing subjects, and (iv) assess the ability of subjects to make a task‐dependent change in the reflex. 2. A continuous random perturbation that did not threaten stability was applied at waist level to nine standing subjects. The effects of the perturbation on ankle torque, ankle movement and soleus electromyographic activity (EMG) were identified by cross‐correlation. The bandwidth of the reflex response and the transmission characteristics of reflexes that respond to ankle movement were identified by spectral analysis. Changes in these reflex responses were investigated when subjects attempted to stand as still as possible, had their eyes closed, or balanced a load equivalent to their own body in a situation in which neither visual nor vestibular reflexes would be activated. 3. When standing, a reflex response coherent with the perturbation was seen in soleus EMG at frequencies up to 5 Hz, with maximal coherence at 1.0‐2.0 Hz. Reflex gain increased with frequency, and there was a frequency‐dependent phase advance of soleus EMG on ankle movement reaching 135 deg at 3 Hz. When attempting to minimize sway, subjects produced a more coherent reflex response and significantly increased reflex gain. 4. The response and transmission characteristics of the lower limb proprioceptive reflex in freely standing subjects were similar to those in subjects balancing a load at the ankle, a situation in which vestibular and visual inputs could not contribute. 5. It is concluded that reflex feedback related to ankle movement contributes significantly to maintaining stance, and that much of the reflex response originates from lower limb mechanoreceptors stimulated by ankle rotation. Although reflex gain may be relatively low during quiet stance it can be increased when necessary to maintain stability.
T-cell receptor–HLA-DRB1 associations suggest specific antigens in pulmonary sarcoidosis

In pulmonary sarcoidosis, CD4+ T-cells expressing T-cell receptor Vα2. 3 accumulate in the lungs of HLA-DRB1*03+ patients. To investigate T-cell receptor-HLA-DRB1*03 interactions underlying recognition of hitherto unknown antigens, we performed detailed analyses of T-cell receptor expression on bronchoalveolar lavage fluid CD4+ T-cells from sarcoidosis patients. Pulmonary sarcoidosis patients (n=43) underwent bronchoscopy with bronchoalveolar lavage. T-cell receptor α and β chains of CD4+ T-cells were analysed by flow cytometry, DNA-sequenced, and three-dimensional molecular models of T-cell receptor-HLA-DRB1*03 complexes generated. Simultaneous expression of Vα2. 3 with the Vβ22 chain was identified in the lungs of all HLA-DRB1*03+ patients. Accumulated Vα2. 3/Vβ22-expressing T-cells were highly clonal, with identical or near-identical Vα2. 3 chain sequences and inter-patient similarities in Vβ22 chain amino acid distribution. Molecular modelling revealed specific T-cell receptor-HLA-DRB1*03-peptide interactions, with a previously identified, sarcoidosis-associated vimentin peptide, (Vim)429–443 DSLPLVDTHSKRTLL, matching both the HLA peptide-binding cleft and distinct T-cell receptor features perfectly. We demonstrate, for the first time, the accumulation of large clonal populations of specific Vα2. 3/Vβ22 T-cell receptor-expressing CD4+ T-cells in the lungs of HLA-DRB1*03+ sarcoidosis patients. Several distinct contact points between Vα2. 3/Vβ22 receptors and HLA-DRB1*03 molecules suggest presentation of prototypic vimentin-derived peptides. Clonal CD4+ lung T-cells associating with HLA-DRB1*03 molecules indicate specific antigens in pulmonary sarcoidosis http://ow.ly/UB81x
Association of the EGFR intron 1 CA repeat length with lung cancer risk

Epidermal growth factor receptor (EGFR) plays an important role in the development and progression of lung cancer. A previous report noted that an increased number of polymorphic CA repeats in the first intron of the EGFR gene results in decreased transcriptional activity. To estimate the association of the length of polymorphic CA repeats in intron 1 of the EGFR gene with lung cancer, a case‐control study of 176 lung cancer patients and 161 controls was conducted in Caucasians. This case‐control study is based on two existing prospective cohorts: the Early Detection Research Network (EDRN) and the Lung Cancer Specialized Program of Research Excellence (SPORE) at the University of Pittsburgh. The frequencies of the SL (one allele>16 repeats), and SS (both allele ≤16 repeats) genotypes were statistically higher among the cases than in the controls (OR: 1.94 and 3.04, 95% CI: 1.16–3.23 and 1.53–6.04, P‐value: 0.01 and 0.001, respectively). When the length of EGFR‐CA repeat was analyzed by the sum of the number of repeats in two alleles, the frequency of the shorter repeats (sum ≤36) was 79.6% versus 63.4%, respectively, and the frequency of the longer repeats (sum >36) was 20.5% versus 36.7%, for lung cancer cases versus controls. The lower sum of EGFR‐CA repeats associated with the risk of lung cancer; the estimated odds ratio was 2.25 with 95% confidence interval: 1.38–3.66 (P = 0.001). Associations involving EGFR‐CA repeat genotype and EGFR‐CA repeat sum remained significant when adjusted for age, gender, and tobacco exposure. Our study, which is preliminary, demonstrates for the first time that shorter EGFR‐CA repeats associate with lung cancer risk. The number of EGFR‐CA repeats identifies a possible susceptible population to lung cancer. © 2007 Wiley‐Liss, Inc.
Invexifying Regularization of Non-Linear Least-Squares Problems

We consider regularization of non-convex optimization problems involving a non-linear least-squares objective. By adding an auxiliary set of variables, we introduce a novel regularization framework whose corresponding objective function is not only provably invex, but it also satisfies the highly desirable Polyak--Lojasiewicz inequality for any choice of the regularization parameter. Although our novel framework is entirely different from the classical $\ell_2$-regularization, an interesting connection is established for the special case of under-determined linear least-squares. In particular, we show that gradient descent applied to our novel regularized formulation converges to the same solution as the linear ridge-regression problem. Numerical experiments corroborate our theoretical results and demonstrate the method's performance in practical situations as compared to the typical $\ell_2$-regularization.
Lack of efficacy of homeopathic therapy against post-calving clinical mastitis in dairy herds in the Waikato region of New Zealand

AIM: To compare clinical and bacteriological cure rates of clinical mastitis following treatment with either antimicrobials or homeopathic preparations. METHODS: Seven spring-calving herds from the Waikato region of New Zealand were used to source cases of clinical mastitis (n = 263 glands) during the first 90 days following calving. Duplicate milk samples were collected for bacteriology from each clinically infected gland at diagnosis and 25 (SD 5.3) days after initial treatment. Affected glands were treated with either an antimicrobial formulation or a homeopathic remedy. Generalised linear models with binomial error distribution and logit link were used to analyse the proportion of cows that were clinical treatment cures and the proportion of glands that were classified as bacteriological cures, based on initial and post-treatment milk samples. RESULTS: Mean cumulative incidence of clinical mastitis was 7% (range 2–13% across herds) of cows. Streptococcus uberis was the most common pathogen isolated from culture-positive samples from affected glands (140/209; 67%). The clinical cure rate was higher for cows treated with antimicrobials (107/113; 95%) than for cows treated with homeopathic remedies (72/114; 63%) (p < 0.001) based on the observance of clinical signs following initial treatment. Across all pathogen types bacteriological cure rate at gland level was higher for those cows treated with antimicrobials (75/102; 74%) than for those treated with a homeopathic preparation (39/107; 36%) (p < 0.001). CONCLUSIONS AND CLINICAL RELEVANCE: Using herds located in the Waikato region of New Zealand, homeopathic remedies had significantly lower clinical and bacteriological cure rates compared with antimicrobials when used to treat post-calving clinical mastitis where S. uberis was the most common pathogen. The proportion of cows that needed retreatment was significantly higher for the homeopathic treated cows. This, combined with lower bacteriological cure rates, has implications for duration of infection, individual cow somatic cell count, costs associated with treatment and animal welfare.
The pattern of cortical atrophy in patients with Parkinson's disease according to cognitive status

Background: Cognitive dysfunction is common in Parkinson's disease (PD), and along with PD with dementia (PDD), the concept of mild cognitive impairment in PD (PD‐MCI) has been introduced. Methods: To identify structural candidates according to cognitive status in PD, we compared gray matter (GM) density across PD‐intact cognition (PD‐IC, n = 23), PD‐MCI (n = 27), and PDD (n = 18) using voxel‐based morphometry. Results: The demographic data among PD subjects were similar, however, general cognition and disease duration were more severe in PD‐MCI and PDD than in PD‐IC. Compared with controls, GM density was significantly decreased in the left occipital area in PD‐IC; the bilateral temporal, left prefrontal and insular, and right occipital areas in PD‐MCI; and in widespread brain areas in PDD. Compared with PD‐IC, patients with PD‐MCI had significantly decreased GM density in the right middle frontal area, and those with PDD had decreased GM density in the right parietal, middle frontal, insular, and lentiform areas. GM density in patients with PDD was significantly decreased in the bilateral middle temporal, right inferior temporal, and left middle and superior prefrontal areas. PDD patients with shorter disease duration before dementia (<5 year) showed greater GM atrophy in the posterior cingulate area than did those with longer disease duration (≥5 year). Conclusions: These data suggest that cortical atrophy in PD exhibits a greater extent with increasing levels of cognitive impairment, and different anatomical substrates would correspond to each cognitive status. © 2011 Movement Disorder Society
Enforcing coordination in network MIMO with unequal CSIT

In this paper1 we consider the Network MIMO channel under the so-called Distributed Channel State Information at the Transmitters (D-CSIT) configuration where the precoder is designed in a distributed manner at each Transmitter (TX) on the basis of local versions of Channel State information (CSI) of various quality. In that setting, a novel transmission scheme has been developed in [1] and surprisingly it was shown that in a so-called regime of weak-CSIT it was possible to achieve a centralized-outerbound obtained when all TXs exchange their local channel estimates. The main novelty of the scheme was the estimation of the interference at the TX having the most accurate CSIT, followed by the quantization and the retransmission of these interference terms using superposition coding. In this work, we develop a new precoding scheme, coined as Hierarchical ZF (HZF), which allows to efficiently exploit the CSI estimates at all the TXs instead of relying on the estimate at a single TX as in [1]. Combining HZF with the transmission scheme of [1], a novel transmission scheme significantly enlarging the so-called weak CSIT regime has been designed. Finally, HZF precoding leads to a stronger interference attenuation as state-of-the-art precoding from the literature and is expected to be useful in other wireless settings with unequal CSIT.
Montelukast for Children with Obstructive Sleep Apnea: Results of a Double-Blind, Randomized, Placebo-Controlled Trial.

RATIONALE Obstructive sleep apnea (OSA) is highly prevalent in children and is usually treated by adenotonsillectomy. Nonsurgical therapies for OSA consist primarily of antiinflammatory approaches and have gained popularity, but their efficacy remains to be critically examined. OBJECTIVES To determine the effect of montelukast on pediatric OSA. METHODS A prospective randomized double-blind controlled trial of polysomnographically diagnosed OSA in children ages 2-10 years who were treated with either oral montelukast (4 or 5 mg daily) or placebo for 16 weeks. Adherence to the medication was ascertained using automated timed pill dispensers along with weekly telephonic reminders. MEASUREMENTS AND MAIN RESULTS Ninety-two children diagnosed with OSA were approached, and 64 (69.6%) agreed to participate. Of these, 57 (89.0%) completed the 16-week trial, 28 in the montelukast group and 29 in the placebo group. Age, sex, and percentage of obesity were similar in the two groups, as were initial apnea-hypopnea index (AHI) scores. Overall, intention-to-treat analyses revealed that beneficial effects occurred in 20 children receiving montelukast (71.4%), whereas only 2 (6.9%) of the children receiving placebo showed reductions in AHI score (P < 0.001). Indeed, AHI decreased from 9.2 ± 4.1/hour total sleep time (TST) to 4.2 ± 2.8/hour TST (P < 0.0001) in montelukast-treated children, whereas in children receiving placebo, the AHI did not change (from 8.2 ± 5.0/h TST before to 8.7 ± 4.9/h TST at completion of the trial). CONCLUSIONS When compared with placebo, montelukast for 16 weeks effectively reduced the severity of obstructive sleep apnea in children 2-10 years of age. These results support a therapeutic role for leukotriene modifiers in pediatric OSA provided that long-term trials confirm current findings. Clinical trial registered with www.clinicaltrials. gov (NCT 00599534).
Preliminary Evidence for Abnormal Cortical Development in Physically and Sexually Abused Children Using EEG Coherence and MRI a

Physical or sexual abuse during childhood has been associated with the development of an array of psychiatric disorders including multiple personality disorder,' borderline personality and refractory psychosis! Childhood physical abuse may also sensitize patients to the later development of posttraumatic stress disorder (PTSD). S We postulated that early deprivation or abuse could result in neurobiological abnormalities responsible for subsequent psychiatric disorders. " Green et al.' found that soft neurological signs and nonspecific EEG abnormalities were more common in abused children. Greens proposed that this was an additional source of trauma amplifying the impact of the abusive environment. Davies9 reported that 17 of 22 sampled survivors of childhood incest had abnormal EEGs, and 36% had clinical seizures. He postulated that this handicap was a risk factor for being sexually abused and exploited by family members. Recently, we hypothesized that early childhood abuse or trauma could affect the development of the cerebral cortex and limbic ~ y s t e m . ~ . ' ~ ' ~
Pathomechanics of Complex Dislocations of the First Metatarsophalangeal Joint

Because only 10 complex dislocations of the first metatarsophalangeal joint have been reported to date, a retrospective review was initiated to study the pathomechanics of 11 new cases (9 patients) and to report on the clinical and functional outcomes. Concomitant ipsilateral injuries were frequent: 6 tarsometatarsal joint partial disruptions and 8 cases with multiple midfoot or forefoot fractures or dislocations occurred. Clinical and radiographic assessments suggested that forefoot hyperextension combined with axial loading of the foot in a heel to toe or toe to heel direction produced all. Six cases required open reductions (5 were compound), and 5 cases were managed by closed methods. Associated tarsometatarsal joint disruptions facilitated closed management. The most common complaints at followup assessment (average, 7 years) were sensitive plantar wounds, partial joint ankylosis, and sesamoid sensitivity. All but 1 patient resumed the same or modified work. The data in this series suggest that most complex dislocations of the first metatarsophalangeal joint probably occur frequently with a concurrent tarsometatarsal joint sprain or disruption, and that the primary mechanism of injury is that of axial loading of the foot causing midfoot hyperflexion and forefoot hyperextension. Contrary to current opinion, not all complex dislocations of the first metatarsophalangeal joint are resistant to closed management.
Advanced Proficiency EHR Training: Effect on Physicians' EHR Efficiency, EHR Satisfaction and Job Satisfaction

The best way to train clinicians to optimize their use of the Electronic Health Record (EHR) remains unclear. Approaches range from web-based training, class-room training, EHR functionality training, case-based training, role-based training, process-based training, mock-clinic training and "on the job" training. Similarly, the optimal timing of training remains unclear--whether to engage in extensive pre go-live training vs. minimal pre go-live training followed by more extensive post go-live training. In addition, the effectiveness of non-clinician trainers, clinician trainers, and peer-trainers, remains unclearly defined. This paper describes a program in which relatively experienced clinician users of an EHR underwent an intensive 3-day Peer-Led EHR advanced proficiency training, and the results of that training based on participant surveys. It highlights the effectiveness of Peer-Led Proficiency Training of existing experienced clinician EHR users in improving self-reported efficiency and satisfaction with an EHR and improvements in perceived work-life balance and job satisfaction.