Miracle-dz/UniFAR-FTUs huggingface dataset:
Spatially Varying Coefficient Inequalities: Evaluating How the Impact of Patient Characteristics on Breast Cancer Survival Varies by Location

An increasing number of studies have identified spatial differences in breast cancer survival. However little is known about whether the structure and dynamics of this spatial inequality are consistent across a region. This study aims to evaluate the spatially varying nature of predictors of spatial inequality in relative survival for women diagnosed with breast cancer across Queensland, Australia. All Queensland women aged less than 90 years diagnosed with invasive breast cancer from 1997 to 2007 and followed up to the end of 2008 were extracted from linked Queensland Cancer Registry and BreastScreen Queensland data. Bayesian relative survival models were fitted using various model structures (a spatial regression model, a varying coefficient model and a finite mixture of regressions model) to evaluate the relative excess risk of breast cancer, with the use of Markov chain Monte Carlo computation. The spatially varying coefficient models revealed that some covariate effects may not be constant across the geographic regions of the study. The overall spatial patterns showed lower survival among women living in more remote areas, and higher survival among the urbanised south-east corner. Notwithstanding this, the spatial survival pattern for younger women contrasted with that for older women as well as single women. This complex spatial interplay may be indicative of different factors impacting on survival patterns for these women.
Climate influence on dengue epidemics in Puerto Rico

The variability of the insect-borne disease dengue in Puerto Rico was studied in relation to climatic variables in the period 1979–2005. Annual and monthly reported dengue cases were compared with precipitation and temperature data. Results show that the incidence of dengue in Puerto Rico was relatively constant over time despite global warming, possibly due to the offsetting effects of declining rainfall, improving health care and little change in population. Seasonal fluctuations of dengue were driven by rainfall increases from May to November. Year-to-year variability in dengue cases was positively related to temperature, but only weakly associated with local rainfall and an index of El Niño Southern Oscillation (ENSO). Climatic conditions were mapped with respect to dengue cases and patterns in high and low years were compared. During epidemics, a low pressure system east of Florida draws warm humid air over the northwestern Caribbean. Long-term trends in past observed and future projected rainfall and temperatures were studied. Rainfall has declined slowly, but temperatures in the Caribbean are rising with the influence of global warming. Thus, dengue may increase in the future, and it will be necessary to anticipate dengue epidemics using climate forecasts, to reduce adverse health impacts.
A 24-year controlled follow-up of patients with silent gallstones showed no long-term risk of symptoms or adverse events leading to cholecystectomy

Abstract Background. The fate of asymptomatic gallstones has not been investigated in many studies with a long-term follow-up. We wanted to examine the subsequent rate of cholecystectomy and gallstone-related symptoms in a population examined in 1983. Methods. Among the persons examined in 1983, unknown (perceived as silent) gallstones were discovered in 20.1% (285/1417) persons. Owing to technical reasons, only 89.9% (1274 persons) of the original study population was retrieved for the present study. Of these, 19.2% (245 persons) had gallstones in 1983 [135 women (55.1%) and 110 men (44.9%), mean age in 1983: 49.9 and 51.3 years, respectively]. Results. Of the 154 still living persons with gallstones from 1983, 134 were traced for follow-up. Of these, 89 underwent a clinical examination and 45 answered a mail or telephone questionnaire. Ultrasonography revealed gallstones in 28.1% (25/89) and 6.7% (9/134) had had the gallbladder removed. 5.5% (5/91) of the deceased patients had had a cholecystectomy. Overall cholecystectomy rate was 6.2%. No link could be shown between the number and the size of gallstones in 1983 and the ultrasonographic demonstration of gallstones in 2007. 43.8% had abdominal pain, and 29.2% had functional abdominal complaints. Conclusions. Unexpectedly, only a minority of persons examined with ultrasonography had present day gallstones without any obvious explanation for this low figure. The rate of cholecystectomy was low in a conservative setting and no adverse events could be ascertained from such a policy.
Selective neurodegeneration, without neurofibrillary tangles, in a mouse model of Niemann‐Pick C disease

The BALB/c mouse model of Niemann‐Pick type C (NPC) disease exhibits neuropathological similarities to the human condition. There is an age‐related cerebral atrophy, demyelination of the corpus callosum, and degeneration of cerebellar Purkinje cells in the NPC mouse. In human NPC, many cortical and subcortical neurons contain neurofibrillary tangles, which are thought by some investigators to play an important role in the neurodegenerative process. The purpose of the present study was to determine whether neurodegeneration occurs in the NPC mouse, in brain regions other than the cerebellum and whether the degeneration is related to the presence of neurofibrillary tangles. Using light microscopic methods with immunohistochemistry, electron microscopy, and cell counting methods, 11‐week‐old NPC+/+ and NPC−/− animals were examined. In the NPC−/− mice, there were 96% fewer Purkinje cells, 28% fewer neurons in the prefrontal cortex, 20% fewer neurons in the thalamus, and 63% fewer glial cells in the corpus callosum. On the other hand, previous studies indicate normal numbers of neurons and glial cells in these same neuroanatomical regions in young NPC−/− mice. There were normal numbers of cholinergic neurons in sections assessed in the striatum and basal forebrain in the 11‐week‐old animals and no evidence of neurofibrillary tangles within cells. The present data indicate that both neurons and glial cells die in the NPC mouse but that all cells are not equally vulnerable. There was no evidence for neurofibrillary tangles in the NPC mouse, and therefore the degenerative process in the mouse is unrelated to the neurofibrillary tangle. J. Comp. Neurol. 433:415–425, 2001. © 2001 Wiley‐Liss, Inc.
One-step rapid reverse transcription-PCR assay for detecting and typing dengue viruses with GC tail and induced fluorescence resonance energy transfer techniques for melting temperature and color multiplexing.

BACKGROUND Dengue fever is an arthropod-borne infection caused by dengue viruses (DVs; DEN-1 to DEN-4). Early diagnosis is critical to prevent severe disease progression and the spreading of DV because no vaccine or specific treatment is available; therefore, a rapid and specific diagnostic assay capable of detecting and typing all serotypes would be ideal. METHODS We amplified RNA samples from all 4 DV serotypes and Japanese encephalitis virus with 4 serotype-specific forward primers and a universal species-specific reverse primer. DEN-1 and DEN-3 forward primers were labeled at their 5' ends with BODIPY 630/650 and Cy5.5, respectively. DEN-1 and DEN-3 amplicons were detected by their characteristic emission generated from induced fluorescence resonance energy transfer. The presence of DEN-2 and DEN-4 amplicons was indicated by SYBR Green I (SGI) signals at specific amplicon melting temperatures (T(m)s). RESULTS Fluorescence signals with specific emission wavelengths were obtained from DEN-1 and DEN-3. SGI melting profiles showed a T(m) difference between DEN-2 and DEN-4 of 4.7 degrees C, which was sufficient for differentiating these 2 serotypes. The primers did not amplify the Japanese encephalitis virus. The detection limits of DEN-1 to DEN-4 were 1.64 x 10(-4), 1.05 x 10(-3), 8.15 x 10(-4), and 5.80 x 10(-3) plaque-forming units per reaction, respectively. The assay had a dynamic range of 10(3)-10(8) plaque-forming units/L and could be performed in 2 h. CONCLUSIONS A single-tube, 1-step reverse transcription-PCR assay based on T(m) and color multiplexing was developed for detecting and typing all 4 DV serotypes.
Residency factors that influence pediatric in-training examination score improvement.

OBJECTIVE The goal of this study was to determine which measurable factors of resident training experience contribute to improvement of in-training examination (ITE) and certifying examination (CE) scores. METHODS This is a descriptive retrospective study analyzing data from July 2003 through June 2006 at a large academic pediatric training program. Pediatric categorical residents beginning residency in July 2003 were included. Regression analyses were used to determine if the number of admissions performed, core lectures attended, acute care topics heard, grand rounds attended, continuity clinic patients encountered, or procedures performed correlated with improvement of ITE scores. These factors were then analyzed in relation to CE scores. RESULTS Seventeen residents were included in this study. The number of general pediatric admissions was the only factor found to correlate with an increase in ITE score (P = .04). Scores for the ITE at pediatric levels 1 and 3 were predictive of CE scores. No other factors measured were found to influence CE scores. CONCLUSIONS Although all experiences of pediatric residents likely contribute to professional competence, some experiences may have more effect on ITE and CE scores. In this study, only general pediatric admissions correlated significantly with an improvement in ITE scores from year 1 to year 3. Further study is needed to identify which elements of the residency experience contribute most to CE success. This would be helpful in optimizing residency program structure and curriculum within the limitations of duty hour regulations.
Intercoalescence Time Distribution of Incomplete Gene Genealogies in Temporally Varying Populations, and Applications in Population Genetic Inference

Tracing back to a specific time T in the past, the genealogy of a sample of haplotypes may not have reached their common ancestor and may leave m lineages extant. For such an incomplete genealogy truncated at a specific time T in the past, the distribution and expectation of the intercoalescence times conditional on T are derived in an exact form in this paper for populations of deterministically time‐varying sizes, specifically, for populations growing exponentially. The derived intercoalescence time distribution can be integrated to the coalescent‐based joint allele frequency spectrum (JAFS) theory, and is useful for population genetic inference from large‐scale genomic data, without relying on computationally intensive approaches, such as importance sampling and Markov Chain Monte Carlo (MCMC) methods. The inference of several important parameters relying on this derived conditional distribution is demonstrated: quantifying population growth rate and onset time, and estimating the number of ancestral lineages at a specific ancient time. Simulation studies confirm validity of the derivation and statistical efficiency of the methods using the derived intercoalescence time distribution. Two examples of real data are given to show the inference of the population growth rate of a European sample from the NIEHS Environmental Genome Project, and the number of ancient lineages of 31 mitochondrial genomes from Tibetan populations.
The PI3K Isoforms p110α and p110δ Are Essential for Pre–B Cell Receptor Signaling and B Cell Development

Different isoforms of phosphatidylinositol 3-kinase have distinct roles in B cell receptor signaling. Relative Importance B cell receptor (BCR) signaling drives the development and survival of B cells and their responses to antigens. Members of the phosphatidylinositol 3-kinase (PI3K) family of lipid kinases mediate BCR signaling. Whereas the p110δ isoform of PI3K is necessary for antigen-dependent BCR signaling, its loss does not affect B cell development in the bone marrow. Ramadani et al. found that, whereas deficiency in individual PI3K isoforms in mice did not prevent early B cell development, deficiency in both p110δ and p110α blocked antigen-independent, so-called tonic, BCR signaling, which was required for B cell development. In contrast, antigen-dependent signaling required p110δ. As Limon and Fruman discuss in the accompanying Perspective, the discovery of this role for p110α suggests that the combined inhibition of p110α and p110δ, rather than of p110δ alone, would be more effective as a therapy to target B cell malignancies that involve chronic BCR signaling. B cell development is controlled by a series of checkpoints that ensure that the immunoglobulin (Ig)–encoding genes produce a functional B cell receptor (BCR) and antibodies. As part of this process, recombination-activating gene (Rag) proteins regulate the in-frame assembly of the Ig-encoding genes. The BCR consists of Ig proteins in complex with the immunoreceptor tyrosine-based activation motif (ITAM)–containing Igα and Igβ chains. Whereas the activation of the tyrosine kinases Src and Syk is essential for BCR signaling, the pathways that act downstream of these kinases are incompletely defined. Previous work has revealed a key role for the p110δ isoform of phosphatidylinositol 3-kinase (PI3K) in agonist-induced BCR signaling; however, early B cell development and mature B cell survival, which depend on agonist-independent or “tonic” BCR signaling, are not substantially affected by a deficiency in p110δ. Here, we show that p110α, but not p110β, compensated in the absence of p110δ to promote early B cell development in the bone marrow and B cell survival in the spleen. In the absence of both p110α and p110δ activities, pre-BCR signaling failed to suppress the production of Rag proteins and to promote developmental progression of B cell progenitors. Unlike p110δ, however, p110α did not contribute to agonist-induced BCR signaling. These studies indicate that either p110α or p110δ can mediate tonic signaling from the BCR, but only p110δ can contribute to antigen-dependent activation of B cells.
Inflammation and Oxidative Stress: The Molecular Connectivity between Insulin Resistance, Obesity, and Alzheimer's Disease

Type 2 diabetes (T2DM), Alzheimer's disease (AD), and insulin resistance are age-related conditions and increased prevalence is of public concern. Recent research has provided evidence that insulin resistance and impaired insulin signalling may be a contributory factor to the progression of diabetes, dementia, and other neurological disorders. Alzheimer's disease (AD) is the most common subtype of dementia. Reduced release (for T2DM) and decreased action of insulin are central to the development and progression of both T2DM and AD. A literature search was conducted to identify molecular commonalities between obesity, diabetes, and AD. Insulin resistance affects many tissues and organs, either through impaired insulin signalling or through aberrant changes in both glucose and lipid (cholesterol and triacylglycerol) metabolism and concentrations in the blood. Although epidemiological and biological evidence has highlighted an increased incidence of cognitive decline and AD in patients with T2DM, the common molecular basis of cell and tissue dysfunction is rapidly gaining recognition. As a cause or consequence, the chronic inflammatory response and oxidative stress associated with T2DM, amyloid-β (Aβ) protein accumulation, and mitochondrial dysfunction link T2DM and AD.
Trends in Testing for Mycobacterium tuberculosis Complex From US Public Health Laboratories, 2009–2013

Objective: We investigated data from US public health laboratories funded through the Centers for Disease Control and Prevention’s Tuberculosis Elimination and Laboratory Cooperative Agreement to document trends and challenges in meeting national objectives in tuberculosis (TB) laboratory diagnoses. Methods: We examined data on workload and turnaround time from public health laboratories’ progress reports during 2009-2013. We reviewed methodologies, laboratory roles, and progress toward rapid detection of Mycobacterium tuberculosis complex through nucleic acid amplification (NAA) testing. We compared selected data with TB surveillance reports to estimate public health laboratories’ contribution to national diagnostic services. Results: During the study period, culture and drug susceptibility tests decreased, but NAA testing increased. Public health laboratories achieved turnaround time benchmarks for drug susceptibility tests at lower levels than for acid-fast bacilli smear and identification from culture. NAA positivity in laboratories among surveillance-reported culture-positive TB cases increased from 26.6% (2355 of 8876) in 2009 to 40.0% (2948 of 7358) in 2013. Public health laboratories provided an estimated 50.9% (4285 of 8413 in 2010) to 57.2% (4210 of 7358 in 2013) of culture testing and 88.3% (6822 of 7727 in 2011) to 94.4% (6845 of 7250 in 2012) of drug susceptibility tests for all US TB cases. Conclusions: Public health laboratories contribute substantially to TB diagnoses in the United States. Although testing volumes mostly decreased, the increase in NAA testing indicates continued progress in rapid M tuberculosis complex detection.
Nasal Passages of Göttingen Minipigs from the Neonatal Period to Young Adult

Histopathological examination of the nasal passages requires a standardized approach for recording lesion distribution patterns. Nasal diagrams provide guidance to map the lesions. Information on lesions exists for rodents, dogs, and monkeys, which all have been used in inhalation studies. Recently, minipigs have garnered interest as an inhalation model because minipigs resemble humans in many features of anatomy, physiology, and biochemistry and may be a good alternative to monkeys and dogs. The present work explored the microanatomy and histology of the nasal passages of Göttingen minipigs from postnatal day 1 until 6 months of age. Six nasal levels were selected, which allow examination of the squamous, transitional (nonciliated) and ciliated respiratory, and olfactory epithelia; the nasopharynx; and relevant structures such as the vomeronasal organ, olfactory bulb, and nasal/nasopharynx-associated lymphoid tissue.
TRANSLATIONAL DIFFUSION OF TRANSIENT RADICALS CREATED BY THE PHOTOINDUCED HYDROGEN ABSTRACTION REACTION IN SOLUTION : ANOMALOUS SIZE DEPENDENCE IN THE RADICAL DIFFUSION

Diffusion coefficients (D) of various radicals created by the photoinduced hydrogen abstraction reactions from alcohols (ethanol and 2‐propanol) are investigated by using the transient grating (TG) method. In all the reaction systems, D’s of the transient radicals, as well as those of the parent molecules, can be measured simultaneously. The results clearly show slower diffusive motions of the radicals, at least of the π radicals in the hydrogen abstraction reaction systems, compared with those of the parent molecules. D’s of the parent molecules usually agree well with the calculated values based on the Spernol and Wirtz modification of the Stokes–Einstein (SE) relation. Although the measured D’s of the radicals are closer to the values predicted by the simple SE equation, the agreements and the ratio of D between the radicals and its parent molecules depend on the molecular size. The ratio becomes closer to unity as the molecular size becomes large. Possible origins of this dependence are discussed.
Action during body perception: Processing time affects self–other correspondences

Abstract The accurate perception of other people and their postures is essential for functioning in a social world. Our own bodies organize information from others to help us respond appropriately by creating self–other mappings between bodies. In this study, we investigated mechanisms involved in the processing of self–other correspondences. Reed and Farah (1995) showed that a multimodal, articulated body representation containing the spatial relations among parts of the human body was accessed by both viewing another's body and moving one's own. Use of one part of the body representation facilitated the perception of homologous areas of other people's bodies, suggesting that inputs from both the self and other activated the shared body representation. Here we investigated whether this self–other correspondence produced rapid facilitation or required additional processing time to resolve competing inputs for a shared body representation. Using a modified Reed and Farah dual-task paradigm, we found that processing time influenced body-position memory: an interaction between body-part moved and body-part attended revealed a relative facilitation effect at the 5 s ISI, but interference at the 2 s ISI. Our results suggest that effective visual-motor integration from the self and other requires time to activate shared portions of the spatial body representation.
Switching from usual brand cigarettes to a tobacco-heating cigarette or snus: Part 2. Biomarkers of exposure

Abstract A randomized, multi-center study of adult cigarette smokers switched to tobacco-heating cigarettes, snus or ultra-low machine yield tobacco-burning cigarettes (50/group) was conducted, and subjects’ experience with the products was followed for 24 weeks. Differences in biomarkers of tobacco exposure between smokers and never smokers at baseline and among groups relative to each other and over time were assessed. Results indicated reduced exposure to many potentially harmful constituents found in cigarette smoke following product switching. Findings support differences in exposure from the use of various tobacco products and are relevant to the understanding of a risk continuum among tobacco products. Trial registration: ClinicalTrials.gov identifier: NCT02061917.
Physiologic rationale for ventilator setting in acute lung injury/acute respiratory distress syndrome patients

ObjectivesTo review the physiologic approach to setting mechanical ventilation in acute lung injury/acute respiratory distress syndrome. Data SourcesMEDLINE search from 1979 to the present. Data SelectionPersonal selection of some articles we believe relevant for understanding acute lung injury/acute respiratory distress syndrome physiopathology and its physiologic management. Data SummaryKnowing the underlying pathology is key to estimating the potential for recruitment. The potential for recruitment is rather low when the consolidation of pulmonary units exceeds collapse, as in diffuse pneumonia. In contrast, when pulmonary unit collapse exceeds consolidation, as in acute lung injury/acute respiratory distress syndrome from extrapulmonary origin, the potential for recruitment may be high. To exploit the potential for recruitment, a transpulmonary pressure greater than the opening pressure must be applied to the lung. To do so, chest wall elastance must be measured or estimated. To avoid collapse after recruitment, a positive end-expiratory pressure greater than the compressive forces operating on the lung and an alveolar ventilation sufficient to prevent absorption atelectasis must be provided. Indeed, avoidance of stretch (low airway plateau pressure) and prevention of cyclic collapse and reopening (adequate positive end-expiratory pressure and alveolar ventilation) are the physiologic cornerstones of mechanical ventilation in acute lung injury/acute respiratory distress syndrome. When considering all the randomized clinical trials reported so far, it is tempting to speculate that transpulmonary pressure and stresses, rather than tidal volume per se, are the key factors that may have an impact on mortality. ConclusionsThe majority of physiologic, experimental, and clinical trial data converge on one simple concept: treat the lung gently.