Deep water pathways in the North Pacific Ocean revealed by Lagrangian particle tracking.

Lagrangian particle tracking experiments are conducted to investigate the pathways of deep water in the North Pacific Ocean. The flow field is taken from a state-of-the-art deep circulation simulation. An unprecedented number of particles are tracked to quantify the volume transport and residence time. Half of the North Pacific deep water returns to the Southern Ocean, and its principal pathway is along the western boundary current in the Southwest Pacific Basin in the deep layer. About 30% is exported to the Indian Ocean after upwelling to the shallow layer in the western North Pacific Ocean. The rest is transported to the Arctic Ocean through the Bering Strait or evaporates within the Pacific Ocean. Upwelling of deep water is confined in the western North Pacific Ocean owing to the strong vertical mixing. The mean residence time of deep water in the North Pacific Ocean is estimated to be several hundred years, which is consistent with the observed radiocarbon distribution.

Prevalence of and risk factors for depressive symptoms in non-tuberculous mycobacterial pulmonary disease.

BACKGROUND: The presence of depressive symptoms in patients with non-tuberculous mycobacterial pulmonary disease (NTM-PD) is an important research topic; however, the prevalence of depressive symptoms and the factors that influence their development are unclear.OBJECTIVE: To analyse the association between CES-D (Center for Epidemiological Studies Depression Scale) scores and clinical parameters such as age, disease duration, pulmonary function, imaging findings, blood data, physical functions, sleep disturbances, respiratory symptoms and health-related quality of life (HRQOL).METHODS: We conducted a cross-sectional retrospective study of 114 patients with NTM-PD at a single centre from March 2016 to January 2021 to evaluate the relationship between CES-D scores and clinical parameters.RESULTS: Participants had a median age of 64 years; 32.5% of them had depressive symptoms. Disease duration, albumin, C-reactive protein, pulmonary function, dyspnoea, exercise capacity, respiratory symptoms, cough-related HRQOL and sleep disturbances were associated with depressive symptoms. Binomial logistic regression analyses indicated that the CES-D score was significantly associated with cough-related HRQOL and sleep disturbances.CONCLUSION: A high percentage of NTM-PD patients in this study experienced depressive symptoms, and these patients had abnormalities of various clinical parameters. Cough-related HRQOL and sleep disturbance had a strong influence on the development of depressive symptoms.

Health-related quality of life associates with clinical parameters in patients with NTM pulmonary disease.

BACKGROUND: Previous studies have shown a reduction in health-related quality of life (HRQoL) in patients with non-tuberculous mycobacterial pulmonary disease (NTM-PD). However, the causes of this decline and the factors that contribute to it are unknown. This study was conducted to analyse the association between the St George´s Respiratory Questionnaire (SGRQ) and clinical parameters, including age, disease duration, body composition, pulmonary function, chest X-ray findings, blood data and physical function.METHODS: We performed a single-centre, cross-sectional, retrospective study of 101 patients with NTM-PD from December 2016 to October 2019. The relationship between the SGRQ scores and clinical parameters was evaluated.RESULTS: The median patient age was 67.0 years. Pulmonary function, radiological score, albumin levels, C-reactive protein levels and incremental shuttle walk test distance (ISWD) were significantly correlated with the total and component scores on the SGRQ. Multiple regression analysis showed that the SGRQ score was significantly associated with radiological score, pulmonary function and ISWD.CONCLUSION: This study was the first to assess the effect of clinical parameters on the SGRQ in patients with NTM-PD. HRQoL as determined using the SGRQ was associated with the radiological score, pulmonary function and ISWD in patients with NTM-PD.

Search for η

We measured missing mass spectrum of the ^{12}C(γ,p) reaction for the first time in coincidence with potential decay products from η^{'} bound nuclei. We tagged an (η+p) pair associated with the η^{'}N→ηN process in a nucleus. After applying kinematical selections to reduce backgrounds, no signal events were observed in the bound-state region. An upper limit of the signal cross section in the opening angle cosθ_{lab}^{ηp}<-0.9 was obtained to be 2.2 nb/sr at the 90% confidence level. It is compared with theoretical cross sections, whose normalization ambiguity is suppressed by measuring a quasifree η^{'} production rate. Our results indicate a small branching fraction of the η^{'}N→ηN process and/or a shallow η^{'}-nucleus potential.

Attenuated relationship between salivary oxytocin levels and attention to social information in adolescents and adults with autism spectrum disorder: a comparative study.

BACKGROUND: Previous research studies have assessed the relationship between attention to social information and peripheral (e.g., plasma and salivary) oxytocin (OT) levels in typically developing (TD) children and children with autism spectrum disorder (ASD). A relationship between them was observed in TD children, but not in children with ASD. However, this relationship remains unexamined in other age groups. To clarify whether this lack of association is maintained throughout development in individuals with ASD, we aimed to assess the relationship between salivary OT levels and attention to social information in adolescents and adults with and without ASD. METHODS: We recruited male adolescents and adults with ASD (n = 17) and TD participants (n = 24). Using the all-in-one eye-tracking system Gazefinder, we measured the percentage fixation time allocated to social information. We also measured the salivary OT levels and Autism Spectrum Quotient (AQ) of participants. Subsequently, we confirmed group differences and conducted a correlation analysis to investigate the relationships between these three measures. RESULTS: Salivary OT levels did not show any significant difference between the ASD and TD groups and were negatively correlated with the AQ in the whole-group analysis, but not in within-group analysis. Individuals with ASD had significantly lower percentage fixation times than did TD individuals for eye regions in human faces with/without mouth motion, for upright biological motion, and for people regions in the people and geometry movies. The percentage of fixation for geometric shapes in the people and geometry movies was significantly higher in the ASD than in the TD group. In the TD group, salivary OT levels were positively correlated with percentage fixation times for upright biological motion and people and negatively correlated with inverted biological motion and geometry. However, no significant correlations were found in the ASD group. CONCLUSIONS: Our exploratory results suggest that salivary OT levels in adolescents and adults with ASD are less indicative of attention to social stimuli than they are in TD adolescents and adults. It is suggested that their association is slightly weaker in adolescents and adults with ASD and that this attenuated relationship appears to be maintained throughout development.

Material stiffness variation in mosquito antennae.

The antennae of mosquitoes are model systems for acoustic sensation, in that they obey general principles for sound detection, using both active feedback mechanisms and passive structural adaptations. However, the biomechanical aspect of the antennal structure is much less understood than the mechano-electrical transduction. Using confocal laser scanning microscopy, we measured the fluorescent properties of the antennae of two species of mosquito- Toxorhynchites brevipalpis and Anopheles arabiensis-and, noting that fluorescence is correlated with material stiffness, we found that the structure of the antenna is not a simple beam of homogeneous material, but is in fact a rather more complex structure with spatially distributed discrete changes in material properties. These present as bands or rings of different material in each subunit of the antenna, which repeat along its length. While these structures may simply be required for structural robustness of the antennae, we found that in FEM simulation, these banded structures can strongly affect the resonant frequencies of cantilever-beam systems, and therefore taken together our results suggest that modulating the material properties along the length of the antenna could constitute an additional mechanism for resonant tuning in these species.

Fluoroquinolones versus trimethoprim-sulfamethoxazole for the treatment of Stenotrophomonas maltophilia infections: a systematic review and meta-analysis.

BACKGROUND: Fluoroquinolones are a popular alternative to trimethoprim-sulfamethoxazole for Stenotrophomonas maltophilia infections. OBJECTIVES: To compare the effects of fluoroquinolones and trimethoprim-sulfamethoxazole on mortality of S. maltophilia infections. DATA SOURCES: PubMed and EMBASE. STUDY ELIGIBILITY CRITERIA: Clinical studies reporting mortality outcomes of S. maltophilia infections. PARTICIPANTS: Patients with clinical infections caused by S. maltophilia. INTERVENTIONS: Fluoroquinolone monotherapy in comparison with trimethoprim-sulfamethoxazole monotherapy. METHODS: Systematic review with meta-analysis technique. RESULTS: Seven retrospective cohort and seven case-control studies were included. Three cohort studies were designed to compare the two drugs, whereas others had other purposes. A total of 663 patients were identified, 332 of which were treated with trimethoprim-sulfamethoxazole (50.1%) and 331 with fluoroquinolones (49.9%). Three cohort studies were designed to compare the effect of the two drugs, whereas the others had other purposes. Levofloxacin was most frequently used among fluoroquinolones (187/331, 56.5%), followed by ciprofloxacin (114/331, 34.4%). The overall mortality rate was 29.6%. Using pooled ORs for the mortality of each study, fluoroquinolone treatment (OR 0.62, 95% CI 0.39-0.99) was associated with survival benefit over trimethoprim-sulfamethoxazole treatment, with low heterogeneity (I2 = 18%). Specific fluoroquinolones such as ciprofloxacin (OR 0.44, 95% CI 0.17-1.12) and levofloxacin (OR 0.78, 95% CI 0.48-1.26) did not show a significant difference in comparison with trimethoprim-sulfamethoxazole. In the sub-group analyses of adult and bacteraemic patients, significant differences in mortality were not observed between fluoroquinolones and trimethoprim-sulfamethoxazole. CONCLUSIONS: Based on a meta-analysis of non-randomized studies, fluoroquinolones demonstrated comparable effects on mortality of S. maltophilia infection to trimethoprim-sulfamethoxazole, supporting the use of fluoroquinolones in clinical S. maltophilia infections. Although the pooled analysis of overall studies favoured fluoroquinolones over trimethoprim-sulfamethoxazole, the studies included were observational, and sub-group analyses of certain fluoroquinolone agents did not show statistical differences with trimethoprim-sulfamethoxazole. Randomized clinical studies are needed to address these issues.

Enterococcal bacteraemia: predictive and prognostic risk factors for ampicillin resistance.

To identify the predictive and prognostic factors associated with ampicillin-resistant enterococcal bacteraemia, we retrospectively reviewed demographic, microbiological and clinical data of patients attending the Kyoto University Hospital, Japan, between 2009 and 2015. Logistic regression and Cox regression analyses were performed to determine the predictive and prognostic factors, respectively. In total, 235 episodes of enterococcal bacteraemia were identified. As ampicillin susceptibility was uniform for Enterococcus faecalis isolates and almost all ampicillin-resistant isolates were E. faecium, bacteraemia due to these species was investigated separately. E. faecalis and E. faecium accounted for 41.7% (98/235) and 48.1% (113/235) of the isolates, respectively and 91.2% of all E. faecium were ampicillin resistant. Nosocomial E. faecium bacteraemia acquisition (odds ratio (OR), 13.6; 95% confidence intervals, 3.16-58.3) was associated with ampicillin-resistant isolates. Bacteraemia from an unknown source (hazard ratio (HR), 2.91; 95% CI 1.36-6.21) and an increased Pitt bacteraemia score (PBS) (HR, 1.36; 95% CI 1.21-1.52) were associated with 30-day mortality in E. faecium infections. Likewise, bacteraemia from an unknown source (HR, 4.17; 95% CI 1.25-13.9) and increased PBS (HR, 1.27; 95% CI 1.09-1.48) were associated with 30-day mortality in patients with E. faecalis bacteraemia. The empirical therapeutic administration of glycopeptides is recommended for patients with bacteraemia from an unknown source in whom severe E. faecium bacteraemia is suspected.

Chiral effects on the final step of an octahedron-shaped coordination capsule self-assembly.

The final step of the self-assembly of an octahedron-shaped coordination capsule was investigated by a novel theoretical method. Two different reaction pathways were detected and classified by the chiral types of constituents, which addressed the possibility of chiral effects on the self-assembly process.

Resuscitative endovascular balloon occlusion of the aorta: what is the optimum occlusion time in an ovine model of hemorrhagic shock?

PURPOSE: The aim of this study is to evaluate the early survival and organ damage following 30 and 60 min of thoracic resuscitative endovascular balloon occlusion of the aorta (REBOA) in an ovine model of severe hemorrhagic shock. METHODS: Eighteen sheep were induced into shock by undergoing a 35 % controlled exsanguination over 30 min. Animals were randomized into three groups: 60-min REBOA 30 min after the bleeding (60-REBOA), 30-min REBOA 60 min after the bleeding (30-REBOA) and no-REBOA control (n-REBOA). Resuscitation with crystalloids and whole blood was initiated 20 and 80 min after the induction of shock. Animals were observed for 24 h with serial potassium and lactate measurements. Autopsy was performed to evaluate organ damage. RESULTS: Two animals of the n-REBOA group died within 90 min of shock induction; no hemorrhagic deaths were observed in the REBOA groups. Twenty-four-hour survival for the 60-, 30-, and n-REBOA groups was 0/6, 5/6, and 4/6 (P = 0.002). In 60-REBOA, potassium and lactate were increased at 270-min time point: from 4.3 to 5.1 mEq/l and from 3.7 to 5.1 mmol/L, respectively. Both these values were significantly higher than in the n-REBOA group (P = 0.029 for potassium and P = 0.039 for lactate). Autopsy revealed acute tubular necrosis in all died REBOA group animals. CONCLUSIONS: In this ovine model of severe hemorrhagic shock, REBOA can be used to prevent early death from hemorrhage; however, 60 min of occlusion results in significant metabolic derangement and organ damage that offsets this gain.

Non-traumatic hemorrhage is controlled with REBOA in acute phase then mortality increases gradually by non-hemorrhagic causes: DIRECT-IABO registry in Japan.

PURPOSE: Resuscitative endovascular balloon occlusion of the aorta (REBOA) is now a feasible and less invasive resuscitation procedure. This study aimed to compare the clinical course of trauma and non-trauma patients undergoing REBOA. METHODS: Patient demographics, etiology, bleeding sites, hemodynamic response, length of critical care, and cause of death were recorded. Characteristics and outcomes were compared between non-trauma and trauma patients. Kaplan-Meier survival analysis was then conducted. RESULTS: Between August 2011 and December 2015, 142 (36 non-trauma; 106 trauma) cases were analyzed. Non-traumatic etiologies included gastrointestinal bleeding, obstetrics and gynecology-derived events, visceral aneurysm, abdominal aortic aneurysm, and post-abdominal surgery. The abdomen was a common bleeding site (69%), followed by the pelvis or extra-pelvic retroperitoneum. None of the non-trauma patients had multiple bleeding sites, whereas 45% of trauma patients did (P < 0.001). No non-trauma patients required resuscitative thoracotomy compared with 28% of the trauma patients (P < 0.001). Non-trauma patients presented a lower 24-h mortality than trauma patients (19 vs. 51%, P = 0.001). The non-trauma cases demonstrated a gradual but prolonged increased mortality, whereas survival in trauma cases rapidly declined (P = 0.009) with similar hospital mortality (68 vs. 64%). Non-trauma patients who survived for 24 h had 0 ventilator-free days and 0 ICU-free days vs. a median of 19 and 12, respectively, for trauma patients (P = 0.33 and 0.39, respectively). Non-hemorrhagic death was more common in non-trauma vs. trauma patients (83 vs. 33%, P < 0.001). CONCLUSIONS: Non-traumatic hemorrhagic shock often resulted from a single bleeding site, and resulted in better 24-h survival than traumatic hemorrhage among Japanese patients who underwent REBOA. However, hospital mortality increased steadily in non-trauma patients affected by non-hemorrhagic causes after a longer period of critical care.

Intravenous immunoglobulin contributes to the control of antimelanoma differentiation-associated protein 5 antibody-associated dermatomyositis with palmar violaceous macules/papules.

Autoantibodies to melanoma differentiation-associated protein 5 (MDA5) are associated with a subset of patients with dermatomyositis (DM) who have rapidly progressive interstitial lung disease (RP-ILD) with poor prognosis. Intensive immunosuppressive therapy is initiated before irreversible lung damage can occur; however, there are few lines of evidence for the treatment of RP-ILD. Here, we report three cases of anti-MDA5 antibody-associated DM with RP-ILD in which the patients were treated with combined-modality therapy, including high-dose prednisolone, tacrolimus, intravenous cyclophosphamide and intravenous immunoglobulin (IVIG). In all three cases, serum ferritin levels, which are known to represent the disease activity of RP-ILD, were decreased after IVIG administration. IVIG might contribute to the control of the disease activity of anti-MDA5 antibody-positive DM. Moreover, palmar violaceous macules/papules around the interphalangeal joints, which was observed in all three cases in the incipient stage, might be a useful sign in suggesting a diagnosis of anti-MDA5 antibody-associated DM.

Therapeutic vaccination based on side population cells transduced by the granulocyte-macrophage colony-stimulating factor gene elicits potent antitumor immunity.

Among cancer immunotherapies, granulocyte-macrophage colony-stimulating factor (GM-CSF) gene-transduced tumor cell vaccine (GVAX) therapies appear promising and have been shown to be safe and effective in multiple clinical trials. However, the antitumor efficacies of GVAX therapy alone are in some cases limited. Here we showed that GVAX therapy targeting cancer stem cells (CSCs) substantially suppressed tumor development in syngeneic immunocompetent mice recapitulating normal immune systems. CSCs were isolated as side population (SP) cells from 4T1 murine breast carcinoma cell line and transduced with GM-CSF gene delivered by non-transmissible Sendai virus (4T1-SP/GM). Impaired tumorigenicity of subcutaneously injected 4T1-SP/GM depended on CD8+ T cells in concert with CD4+ T cells and natural killer cells. Mice therapeutically vaccinated with irradiated 4T1-SP/GM cells had markedly suppressed tumor development of subcutaneously transplanted 4T1-SP cells compared with those treated with irradiated cells of non-transduced 4T1-SP cells or non-SP (4T1-NSP/GM) cells. Tumor suppression was accompanied by the robust accumulation of mature dendritic cells at vaccination sites and T-helper type 1-skewed systemic cellular immunity. Our results suggested that CSC cell-based GVAX immunotherapy might be clinically useful for inducing potent tumor-specific antitumor immunity.

Erratum to: Seasonal trend and clinical presentation of Bacillus cereus bloodstream infection: association with summer and indwelling catheter.

Bacillus cereus, an opportunistic pathogen, can cause fatal infection. However, B. cereus bloodstream infections (BSIs) have not been well characterised. From 2008 to 2013, B. cereus isolates from all of the specimens and patients with B. cereus BSIs were identified. Environmental samples were collected to detect B. cereus contamination. We also characterised the clinical presentation of B. cereus BSI through analyses of risk factors for BSI and mortality. A total of 143 clinical B. cereus isolates was detected. Fifty-one patients with nosocomial infections were diagnosed as B. cereus BSI, and 37 had contaminated blood cultures. The number of B. cereus isolates and BSI patients was significantly greater from June to September than from January to April (3.4 vs. 1.0 per month and 1.4 vs. 0.2, respectively). All BSIs were nosocomial and related to central or peripheral vascular catheter. Urinary catheter [odds ratio (OR) 6.93, 95 % confidence interval (CI) 2.40-20.0] was the independent risk factor associated with BSI patients when compared to patients regarded as contaminated. In-hospital mortality among BSI patients was 20 % and was associated with urinary catheter (OR 12.3, 95 % CI 0.67-225, p=0.045) and higher Charlson index (OR 1.99, 95 % CI 1.26-3.12). The number of B. cereus isolates and BSI increased during summer. Inpatients with indwelling vascular or urinary catheters should be carefully monitored for potential B. cereus BSIs.

Development and evaluation of MALDI-TOF MS-based serotyping for Streptococcus pneumoniae.

Surveillance of Streptococcus pneumoniae serotypes is important for the successful implementation of vaccination strategies to prevent the spread of invasive pneumococcal diseases. The standard method of serotyping of pneumococcal isolates is the phenotypic Neufeld test, which is cost- and labor-intensive. Recently, matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS) has been implemented as a rapid, simple and inexpensive method for identifying species. We evaluated the performance of MALDI-TOF MS for serotyping ten major serotypes of S. pneumoniae in Japan (serotypes 3, 6B, 15A, 15C, 19A, 19 F, 23A, 24 F, 35B and 38) using the Biotyper and ClinProTools. After optimizing the settings, we validated their serotyping performance for serotypes 3, 15A and 19A using a separate set of isolates that were not used in the creation of the classification algorithms. A total of 574 isolates of S. pneumoniae collected from Japanese nationwide surveillance studies were included. Of these, 407 isolates belonged to the ten major serotypes. Biotyper and ClinProTools correctly identified 77.9 % and 84.0 %, respectively, of the ten major serotype isolates. The validation analysis included a total of 113 isolates of the serotypes 3, 15A and 19A isolates. Biotyper and ClinProTools correctly identified 85.0 % and 69.9 % of the validation cohort isolates, respectively. MALDI-TOF MS has the potential to discriminate the ten major S. pneumoniae serotypes prevalent in Japan.

Seasonal trend and clinical presentation of Bacillus cereus bloodstream infection: association with summer and indwelling catheter.

Bacillus cereus, an opportunistic pathogen, can cause fatal infection. However, B. cereus bloodstream infections (BSIs) have not been well characterised. From 2008 to 2013, B. cereus isolates from all of the specimens and patients with B. cereus BSIs were identified. Environmental samples were collected to detect B. cereus contamination. We also characterised the clinical presentation of B. cereus BSI through analyses of risk factors for BSI and mortality. A total of 217 clinical B. cereus isolates was detected. Fifty-one patients with nosocomial infections were diagnosed as B. cereus BSI, and 37 had contaminated blood cultures. The number of B. cereus isolates and BSI patients was significantly greater from June to September than from January to April (4.9 vs. 1.5 per month and 1.2 vs. 0.2, respectively). All BSIs were nosocomial and related to central or peripheral vascular catheter. Urinary catheter [odds ratio (OR) 6.93, 95% confidence interval (CI) 2.40-20.0] was the independent risk factor associated with BSI patients when compared to patients regarded as contaminated. In-hospital mortality among BSI patients was 20% and was associated with urinary catheter (OR 34.7, 95 % CI 1.89-63.6) and higher Charlson index (OR 1.99, 95 % CI 1.26-3.12). The number of B. cereus isolates and BSI increased during summer. Inpatients with indwelling vascular or urinary catheters should be carefully monitored for potential B. cereus BSIs.

Itraconazole prophylaxis for invasive Aspergillus infection in lung transplantation.

Invasive Aspergillus infection (IA) is a significant cause of morbidity in lung transplantation (LT). However, its optimal prophylaxis is unclear. We routinely administer itraconazole (ITCZ) prophylaxis to all patients undergoing LT. In this study, we retrospectively evaluated the duration of prophylaxis and risk factors of IA. Among 30 adult patients who underwent LT, 5 patients developed IA. All patients with IA stopped ITCZ treatment within 1 year. At least 1 year of ITCZ prophylaxis is essential for the prevention of IA. Cytomegalovirus infection, renal replacement therapy, and tracheotomy were risk factors for IA.

A randomized phase III trial of postoperative adjuvant therapy for completely resected stage IA-IIIA lung cancer using an anti­angiogenetic agent: irsogladine maleate.

AIM: Although angiogenesis plays an important role in the invasion and metastasis of solid tumors, very few anti-angiogenetic drugs have been developed. Reexamining the anti-angiogenetic effects of existing drugs such as Thalidomide is another possible strategy for drug discovery. Irsogladine maleate (IM) is a drug invented to treat gastric ulcers; however, several reports have shown that IM also exerts anti-angiogenetic effects in vitro, in vivo and in humans. In order to elucidate whether treatment with IM would improve the prognoses of patients with resected lung cancer, we conducted a randomized trial. METHODS: In the control group, uracil-tegafur (250 mg/m2/day) was administered for two years to patients with resected stage IB - IIIA lung cancer, and no adjuvant therapy was administered to those with stage IA disease. In the study group, IM (4 mg/body/day) was additionally administered for two years. RESULTS: No significant differences were observed in the major prognostic factors among 305 eligible patients between the study and control groups. Adverse effects were minimal. The overall survival of the patients in the study and control groups were not statistically different. When the analysis was stratified by regimen, among the patients with resected stage IA disease, disease-specific survival in the study group was slightly higher than that in the control group; however, the difference was not significant (p=0.07). CONCLUSION: Although it could not be proven that IM improves the prognoses of resected lung cancer patients, IM might have some effect on resected stage IA disease, and another trial should be conducted.