First report of suspected glycogen storage disease type 1a occurring in an adult dog.

A 4-year-old female border collie was presented with haemoabdomen following the rupture of a hepatocellular carcinoma. After referral for ongoing elevation of alanine aminotransferase and alkaline phosphatase, the dog was found to have marked vacuolar hepatopathy due to glycogen accumulation within the liver, fasting hypoglycaemia and hyperlactataemia, and a negative response to glucagon stimulation testing. These changes were strongly suggestive of glycogen storage disease type 1a. Based on our literature search, this report documents the first adult canine to be diagnosed with suspected glycogen storage disease type 1a.

Comparison of Mycobacterium tuberculosis complex Yield and Contamination Rates using Lowenstein-Jensen with and without Antibiotics in Western Kenya.

Background: While molecular methods have been recently endorsed for diagnosis of tuberculosis (TB), mycobacterial culture remains the gold standard. Lowenstein-Jensen (LJ) is often used for the cultivation of Mycobacterium tuberculosis complex (MTBC); however contamination often renders a subset of cultures useless. We compared the MTBC yield and contamination rate of processed sputum inoculated on LJ with antibiotics (LJ PACT) to LJ without antibiotics (LJ). Methodology: Sputum samples were obtained from people living with HIV enrolled in a TB screening study in western Kenya, processed using NALC/NaOH-Na citrate, then inoculated on LJ PACT and LJ media. Cultures were evaluated weekly with growth identified as acid-fast bacilli by Ziehl-Neelsen bright-field microscopy. MTBC and nontuberculous mycobacteria (NTM) were identified by immunochromatographic and line probe assays. Results: A total of 700 sputum samples were cultured on both LJ PACT and LJ between March and June 2012. Of those cultured on LJ PACT, 29 (4.1%) grew MTBC, 613 (87.6%) were negative, 12 (1.7%) grew NTM, and 46 (6.6%) were contaminated; on LJ, 28 (4%) grew MTBC, 553 (79%) were negative, 9 (1.3%) grew NTM, and 110 (15.7%) were contaminated. The difference in contamination on LJ PACT and LJ was statistically significant (p<0.0001), while the difference in MTBC growth was not (p=0.566).

Improved search for Muon-neutrino to electron-neutrino oscillations in MINOS.

We report the results of a search for ν(e) appearance in a ν(µ) beam in the MINOS long-baseline neutrino experiment. With an improved analysis and an increased exposure of 8.2 × 10(20) protons on the NuMI target at Fermilab, we find that 2 sin(2) (θ(23))sin(2)(2θ(13))<0.12(0.20) at 90% confidence level for δ = 0 and the normal (inverted) neutrino mass hierarchy, with a best-fit of 2sin(2) (θ(23))sin(2)(2θ(13)) = 0.041(-0.031)(+0.047) (0.079(-0.053) (+0.071)). The θ(13) = 0 hypothesis is disfavored by the MINOS data at the 89% confidence level.

Active to sterile neutrino mixing limits from neutral-current interactions in MINOS.

Results are reported from a search for active to sterile neutrino oscillations in the MINOS long-baseline experiment, based on the observation of neutral-current neutrino interactions, from an exposure to the NuMI neutrino beam of 7.07×10(20) protons on target. A total of 802 neutral-current event candidates is observed in the Far Detector, compared to an expected number of 754 ± 28(stat) ± 37(syst) for oscillations among three active flavors. The fraction f(s) of disappearing ν(µ) that may transition to ν(s) is found to be less than 22% at the 90% C.L.

First direct observation of muon antineutrino disappearance.

This Letter reports the first direct observation of muon antineutrino disappearance. The MINOS experiment has taken data with an accelerator beam optimized for ν(µ) production, accumulating an exposure of 1.71 × 10²° protons on target. In the Far Detector, 97 charged current ν(µ) events are observed. The no-oscillation hypothesis predicts 156 events and is excluded at 6.3σ. The best fit to oscillation yields |Δm²| = [3.36(-0.40)(+0.46)(stat) ± 0.06(syst)] × 10⁻³ eV², sin²(2θ) = 0.86(-0.12)(+0.11)(stat) ± 0.01(syst). The MINOS ν(µ) and ν(µ) measurements are consistent at the 2.0% confidence level, assuming identical underlying oscillation parameters.

Measurement of the neutrino mass splitting and flavor mixing by MINOS.

Measurements of neutrino oscillations using the disappearance of muon neutrinos from the Fermilab NuMI neutrino beam as observed by the two MINOS detectors are reported. New analysis methods have been applied to an enlarged data sample from an exposure of 7.25×10(20) protons on target. A fit to neutrino oscillations yields values of |Δm(2)|=(2.32(-0.08)(+0.12))×10(-3) eV(2) for the atmospheric mass splitting and sin(2)(2θ)>0.90 (90% C.L.) for the mixing angle. Pure neutrino decay and quantum decoherence hypotheses are excluded at 7 and 9 standard deviations, respectively.

Evaluation of an international training course to build programmatic capacity for tuberculosis control.

We evaluated the international training course of the Research Institute of Tuberculosis, Kiyose, Japan, by e-mailing structured questionnaires to participants who attended the course from 2001 to 2007. Of 62 responding participants, 34 developed action plan projects (APPs) and 28 developed operations research projects (ORPs). Among respondents drafting APPs, 27 (79%) started implementing projects, and 24 (88%) completed over half of their planned activities. Among respondents drafting ORPs, 11 (39%) started projects but no scientific papers were published. The main reasons for the failure to implement ORPs were due to lack of time, funds, and disapproval by supervisors. A sequential training model may better address barriers to teaching and assisting ORPs.

Search for Lorentz invariance and CPT violation with the MINOS far detector.

We searched for a sidereal modulation in the MINOS far detector neutrino rate. Such a signal would be a consequence of Lorentz and CPT violation as described by the standard-model extension framework. It also would be the first detection of a perturbative effect to conventional neutrino mass oscillations. We found no evidence for this sidereal signature, and the upper limits placed on the magnitudes of the Lorentz and CPT violating coefficients describing the theory are an improvement by factors of 20-510 over the current best limits found by using the MINOS near detector.

Characterization of mast cell subtypes, distribution, and antigen-induced activation in the guinea pig esophagus.

The number of esophageal mucosa mast cells (MCs) increases in allergic and inflammation conditions in the esophagus, but their role in these conditions is less clear. MCs are derived from bone marrow, migrate and mature in the peripheral tissues. Two subsets of MCs have been characterized as mucosal MC (MMC) and connective tissue MC (CTMC) defined by anatomic location, granule contents, and functions. Whether esophageal MCs share typical features with either MMC or CTMC has yet to be determined. This study characterized esophageal MCs subtypes, distribution, antigen-induced sensitization, and degranulation as measured by MC staining and histamine release assay. Immunofluorescent double staining of MC tryptase and chymase were performed in the esophagus, intestine, and skin from normal and ovalbumin (OVA) actively sensitized guinea pigs. Histamine release was measured in the esophagus from OVA-sensitized guinea pigs following in vitro antigen challenge. Similar to the MCs in the intestine and skin, esophageal MCs contained three subtypes, which included 62% MCtc (tryptase+/chymase+), 17% MCc (chymase+/tryptase-), and 21% MCt (tryptase+/chymase-). In contrast to the ileal MCs, which were distributed all over the mucosa, submucosa, and serosa, MCs in the esophagus almost all (more than 98%) lined along the lamina propria. OVA active sensitization significantly increased the esophageal MC subtype MCtc. OVA in vitro challenge of the esophagus from sensitized guinea pig significantly decreased tryptase-positive MC subtypes MCtc and MCt, and released a significant amount of tissue histamine content. In conclusion, MCs in the guinea pig esophagus have unique features in immunophenotypes, distribution, and degranulation response to OVA challenge with the release of significant amounts of proteases and histamine into the tissue. These characteristics may indicate that OVA in vitro challenge in OVA-sensitized guinea pig esophagus could be a good model to study the role of esophageal MCs in allergic and inflammation conditions.

Search for muon-neutrino to electron-neutrino transitions in MINOS.

This Letter reports on a search for nu(mu) --> nu(e) transitions by the MINOS experiment based on a 3.14x10(20) protons-on-target exposure in the Fermilab NuMI beam. We observe 35 events in the Far Detector with a background of 27+/-5(stat)+/-2(syst) events predicted by the measurements in the Near Detector. If interpreted in terms of nu(mu) --> nu(e) oscillations, this 1.5sigma excess of events is consistent with sin2(2theta(13)) comparable to the CHOOZ limit when |Delta m2|=2.43x10(-3) eV2 and sin2(2theta(23))=1.0 are assumed.

Search for active neutrino disappearance using neutral-current interactions in the MINOS long-baseline experiment.

We report the first detailed comparisons of the rates and spectra of neutral-current neutrino interactions at two widely separated locations. A depletion in the rate at the far site would indicate mixing between nu(mu) and a sterile particle. No anomalous depletion in the reconstructed energy spectrum is observed. Assuming oscillations occur at a single mass-squared splitting, a fit to the neutral- and charged-current energy spectra limits the fraction of nu(mu) oscillating to a sterile neutrino to be below 0.68 at 90% confidence level. A less stringent limit due to a possible contribution to the measured neutral-current event rate at the far site from nu(e) appearance at the current experimental limit is also presented.

Testing Lorentz invariance and CPT conservation with NuMI neutrinos in the MINOS near detector.

A search for a sidereal modulation in the MINOS near detector neutrino data was performed. If present, this signature could be a consequence of Lorentz and CPT violation as predicted by the effective field theory called the standard-model extension. No evidence for a sidereal signal in the data set was found, implying that there is no significant change in neutrino propagation that depends on the direction of the neutrino beam in a sun-centered inertial frame. Upper limits on the magnitudes of the Lorentz and CPT violating terms in the standard-model extension lie between 10(-4) and 10(-2) of the maximum expected, assuming a suppression of these signatures by a factor of 10(-17).

Measurement of neutrino oscillations with the MINOS detectors in the NuMI beam.

This Letter reports new results from the MINOS experiment based on a two-year exposure to muon neutrinos from the Fermilab NuMI beam. Our data are consistent with quantum-mechanical oscillations of neutrino flavor with mass splitting |Deltam2| = (2.43+/-0.13) x 10(-3) eV2 (68% C.L.) and mixing angle sin2(2theta) > 0.90 (90% C.L.). Our data disfavor two alternative explanations for the disappearance of neutrinos in flight: namely, neutrino decays into lighter particles and quantum decoherence of neutrinos, at the 3.7 and 5.7 standard-deviation levels, respectively.

Time and PSA threshold model prognosticates long-term overall and disease-specific survival in prostate cancer patients as early as 3 months after external beam radiation therapy.

The specific aim of this analysis was to evaluate the capability of a time and prostate-specific antigen (PSA) threshold model to prognosticate overall survival (OS) and disease-specific survival (DSS) based on early PSA kinetics after radiotherapy for prostate cancer by retrospective review of outcomes in 918 patients. Crossing below analyzed PSA thresholds at specific defined time points reduced disease-specific death hazard ratios to relative to the cohort above threshold. The time and PSA threshold model demonstrates the ability to prognosticate OS and DSS as early as 3 months post-radiotherapy for prostate cancer.

Computed tomography scan versus ventilation-perfusion lung scan in the detection of pulmonary embolism.

This study compared the sensitivity and specificity of computed tomography (CT) scan and ventilation-perfusion (V-P) scan in detecting pulmonary embolism (PE) with pulmonary angiogram (AG) as the reference standard. Following a comprehensive search of the indexed medical literature, CT scan studies related to PE diagnosis were systematically evaluated to select those using AG as the reference standard and meeting specified methodologic criteria. Studies were further grouped by those reporting results for central PE findings only versus central and peripheral PE combined. A composite analysis of data derived from seven selected publications yielded sensitivity and specificity estimates for CT scan in detecting PE, which were statistically compared to the published results of a multi-center study reporting the sensitivity and specificity of the V-P scan with pulmonary AG as the reference standard. The calculated CT scan sensitivity was 77% for central PE only data and 81% for central and peripheral PE combined data, and the CT scan specificity was 91% and 98%, respectively. High-probability V-P scan sensitivity was 41% and specificity 97%; high- and intermediate-probability V-P scans combined yielded sensitivity 83% and specificity 52%. The sensitivity for PE detection was significantly greater for CT scan than for high-probability V-P scan; CT scan sensitivity was equivalent to V-P when high- and intermediate-probability scans were considered together. CT scan specificity for central and peripheral PE combined was equivalent to that of the high-probability V-P scan, but significantly greater than that of high- and intermediate-probability V-P scans considered together. Considering that only a small proportion of patients with suspected PE yield high-probability V-P scan results (which are usually indicative of PE), while as many as one-half of patients may yield intermediate-probability results (which are commonly not useful in PE diagnosis), our results suggest the CT scan may be an appropriate study for use by Emergency Physicians in the clinical evaluation of suspected PE.

Medical illness, past depression, and present depression: a predictive triad for in-hospital mortality.

OBJECTIVE: The authors' objectives were to determine 1) whether major depressive disorder diagnosed according to DSM-IV criteria modified for the medically ill predicted in-hospital mortality better than major depressive disorder diagnosed according to inclusive DSM-IV criteria and 2) whether a history of depression and current depression predicted mortality independent of severity of physical illness. METHOD: Of 392 consecutive medical inpatients, 241 were interviewed within the first 3 days of admission and 151 were excluded from the study. Chart review and a clinical interview that included the Schedule for Affective Disorders and Schizophrenia were used to determine demographic variables, past psychiatric history, psychiatric diagnoses, and illness measures. Diagnoses included major depressive disorder and minor depression diagnosed according to DSM-IV criteria that included all symptoms regardless of etiology and according to criteria modified for the medically ill (hopelessness, depression, or anhedonia were used as the qualifying affective symptoms; depressive symptoms were eliminated if easily explained by medical illness, treatments, or hospitalization). The Charlson combined age-comorbidity index was used to measure severity of illness. RESULTS: A diagnosis of major depressive disorder based on criteria modified for patients with medical illness better predicted mortality than a diagnosis based on inclusive criteria. A past history of depression and the Charlson combined age-comorbidity index predicted in-hospital mortality, but demographic variables, pain, discomfort, length of stay, medical diagnoses, and minor depression did not. In the final multivariate logistic regression model, the Charlson combined age-comorbidity index, a modified diagnosis of major depressive disorder, and a history of depression were independent predictors of in-hospital death. CONCLUSIONS: Severity of medical illness, a diagnosis of major depressive disorder based on modified criteria, and a past history of depression independently predicted in-hospital mortality in medical inpatients.

Association between depressive symptoms and mortality in medical inpatients.

The authors interviewed a consecutive series of medical inpatients (N = 241) using the Schedule for Affective Disorders and Schizophrenia to determine which depressive symptoms are associated with in-hospital mortality. Fifteen depressive symptoms, pain, and physical discomfort were assessed along with medical comorbidity. Twenty patients died in-hospital (8.3%). Logistic regression showed that anhedonia, hopelessness, worthlessness, indecisiveness, and insomnia predicted in-hospital death after adjusting for physical comorbidity and age. Clinicians should be aware that these depressive symptoms may predict mortality in medical inpatients. Future studies should address which treatment modalities lead to better outcomes.

Relationships among student and graduate caring ability and professional school climate.

This study represents the second phase in a longitudinal study of the development of caring ability in registered nurses. A nationwide sample of female graduates of US baccalaureate nursing programs was resurveyed 3 years after the phase-one survey taken during nursing school. The purpose of the study was to continue an evaluation of several variables contributing to the development of professional caring ability. Previously validated instruments were used to measure caring ability (Caring Ability Inventory), maternal and paternal care (Parental Bonding Instrument), and the caring climate of the respective nursing schools (Charles F. Kettering Ltd. School Climate Profile). Although parental bonding scores remained unchanged from the initial survey, caring ability scores significantly increased after entry into practice (paired student's t test, P < .001). The strongest predictor of postgraduate caring ability was student caring ability scores (r = .58, P < .001). When student caring ability scores were excluded as a potential predictor during stepwise multiple regression analysis, school climate scores were the strongest predictor of postgraduate caring ability (r = .17, P < .05). This suggests that development of professional caring ability is related to caring school environments. Furthermore, caring ability as a student predicts further development of caring ability after entry into practice.

Graduate medical education costs in nonacademic health center teaching hospitals: evidence from Maryland.

As managed care has grown, much concern has been expressed about the potential plight of the nation's 125 academic health centers (AHCs). Less concern has focused on non-AHC teaching hospitals, although most studies of graduate medical education (GME) costs include these hospitals in their estimates. While most studies have found that costs increase positively with various measures of "teaching intensity," some have concluded that hospitals with smaller programs have costs that are the same or less than comparable nonteaching hospitals. However, few studies have tested whether AHCs' cost structures are sufficiently similar to those of other hospitals to reliably include them in the same estimation. This article tests that assumption for Maryland hospitals, finds it violated, and presents results for non-AHC teaching hospitals. The results reveal that, at least in Maryland, even small teaching programs add to hospital costs.

Effects of a pneumonia clinical pathway on time to antibiotic treatment, length of stay, and mortality.

OBJECTIVES: A clinical pathway standardizing management for patients with an admission diagnosis of pneumonia was initiated after a previous study found delayed time to initial antibiotic administration, a longer length of stay, and higher mortality rate for the authors' patients as compared with those in a "benchmark" hospital. The current study was undertaken to determine whether implementation of the clinical pathway resulted in statistically significant decreases for these measures, both in the initial year following pathway implementation and two years later. METHODS: A retrospective chart review was completed for three cohorts of pneumonia patients admitted via the ED: 1) three months immediately prior to pathway implementation, 2) 10-12 months after implementation of the pathway, and 3) 34-36 months after implementation of the pathway. Four standard antibiotic regimens were used following pathway implementation: community-acquired, community-acquired penicillin-allergic, nursing home-acquired, and nursing home-acquired penicillin-allergic. Demographics, medical history, presentation signs and symptoms, process of care, and outcome data were abstracted from each patient's medical record. RESULTS: The mean time to antibiotic administration decreased from 315 minutes prepathway to approximately 175 minutes during the first postpathway period and 171 minutes at three years (ANOVA, p < 0.0001). The percentage of patients who received antibiotics in the ED increased from 58% prepathway to 94% during the first postpathway period and 97% at three years (chi square, p < 0.0001). Length of stay decreased from 9.7 prepathway to 8.9 days during the first postpathway period and 6.4 days at three years (ANOVA, p < 0.0001). There was no significant change of in-hospital mortality (9.6% prepathway to 5.2% and 4.9%) in the two respective periods. CONCLUSIONS: This study demonstrates that implementation of a pneumonia clinical pathway for the management of hospitalized patients admitted via the ED decreases the time to initial antibiotic treatment and increases the proportion of patients initially treated with antibiotics in the ED. These effects were evident in the first year following pathway implementation and sustained at the three-year study interval.