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  1. Pembrolizumab monotherapy versus chemotherapy in platinum-pretreated, recurrent or metastatic nasopharyngeal cancer (KEYNOTE-122): an open-label, randomized, phase III trial
    Chan ATC, Lee VHF, Hong RL, Ahn MJ, Chong WQ, Kim SB, et al.
    Ann Oncol, 2023 Mar;34(3):251-261.
    PMID: 36535566 DOI: 10.1016/j.annonc.2022.12.007
    BACKGROUND: Pembrolizumab previously demonstrated robust antitumor activity and manageable safety in a phase Ib study of patients with heavily pretreated, programmed death ligand 1 (PD-L1)-positive, recurrent or metastatic nasopharyngeal carcinoma (NPC). The phase III KEYNOTE-122 study was conducted to further evaluate pembrolizumab versus chemotherapy in patients with platinum-pretreated, recurrent and/or metastatic NPC. Final analysis results are presented.

    PATIENTS AND METHODS: KEYNOTE-122 was an open-label, randomized study conducted at 29 sites, globally. Participants with platinum-pretreated recurrent and/or metastatic NPC were randomly assigned (1 : 1) to pembrolizumab or chemotherapy with capecitabine, gemcitabine, or docetaxel. Randomization was stratified by liver metastasis (present versus absent). The primary endpoint was overall survival (OS), analyzed in the intention-to-treat population using the stratified log-rank test (superiority threshold, one-sided P = 0.0187). Safety was assessed in the as-treated population.

    RESULTS: Between 5 May 2016 and 28 May 2018, 233 participants were randomly assigned to treatment (pembrolizumab, n = 117; chemotherapy, n = 116); Most participants (86.7%) received study treatment in the second-line or later setting. Median time from randomization to data cut-off (30 November 2020) was 45.1 months (interquartile range, 39.0-48.8 months). Median OS was 17.2 months [95% confidence interval (CI) 11.7-22.9 months] with pembrolizumab and 15.3 months (95% CI 10.9-18.1 months) with chemotherapy [hazard ratio, 0.90 (95% CI 0.67-1.19; P = 0.2262)]. Grade 3-5 treatment-related adverse events occurred in 12 of 116 participants (10.3%) with pembrolizumab and 49 of 112 participants (43.8%) with chemotherapy. Three treatment-related deaths occurred: 1 participant (0.9%) with pembrolizumab (pneumonitis) and 2 (1.8%) with chemotherapy (pneumonia, intracranial hemorrhage).

    CONCLUSION: Pembrolizumab did not significantly improve OS compared with chemotherapy in participants with platinum-pretreated recurrent and/or metastatic NPC but did have manageable safety and a lower incidence of treatment-related adverse events.

  2. Fulltext Asian Best Practices for Care of Diabetes in Elderly (ABCDE)
    Kalra S, Dhar M, Afsana F, Aggarwal P, Aye TT, Bantwal G, et al.
    Rev Diabet Stud, 2022 Jun 30;18(2):100-134.
    PMID: 35831938 DOI: 10.1900/RDS.2022.18.100
    The elderly population with diabetes is diverse with the majority experiencing a decline in physical and mental capabilities, impacting the entire diabetes management process. Therefore, a need for geriatric-specific guidelines, especially for the Asian population, was identified and subsequently developed by an expert panel across government and private institutions from several Asian countries. The panel considered clinical evidence (landmark trials, position papers, expert opinions), recommendations from several important societies along with their decades of clinical experience and expertise, while meticulously devising thorough geriatric-specific tailored management strategies. The creation of the ABCDE best practices document underscores and explores the gaps and challenges and determines optimal methods for diabetes management of the elderly population in the Asian region.
  3. Fulltext Two decades of neuroscience publication trends in Africa
    Maina MB, Ahmad U, Ibrahim HA, Hamidu SK, Nasr FE, Salihu AT, et al.
    Nat Commun, 2021 Jun 08;12(1):3429.
    PMID: 34103514 DOI: 10.1038/s41467-021-23784-8
    Neuroscience research in Africa remains sparse. Devising new policies to boost Africa's neuroscience landscape is imperative, but these must be based on accurate data on research outputs which is largely lacking. Such data must reflect the heterogeneity of research environments across the continent's 54 countries. Here, we analyse neuroscience publications affiliated with African institutions between 1996 and 2017. Of 12,326 PubMed indexed publications, 5,219 show clear evidence that the work was performed in Africa and led by African-based researchers - on average ~5 per country and year. From here, we extract information on journals and citations, funding, international coauthorships and techniques used. For reference, we also extract the same metrics from 220 randomly selected publications each from the UK, USA, Australia, Japan and Brazil. Our dataset provides insights into the current state of African neuroscience research in a global context.
  4. Fulltext Graphene Sensor Arrays for Rapid and Accurate Detection of Pancreatic Cancer Exosomes in Patients' Blood Plasma Samples
    Yin T, Xu L, Gil B, Merali N, Sokolikova MS, Gaboriau DCA, et al.
    ACS Nano, 2023 Aug 08;17(15):14619-14631.
    PMID: 37470391 DOI: 10.1021/acsnano.3c01812
    Biosensors based on graphene field effect transistors (GFETs) have the potential to enable the development of point-of-care diagnostic tools for early stage disease detection. However, issues with reproducibility and manufacturing yields of graphene sensors, but also with Debye screening and unwanted detection of nonspecific species, have prevented the wider clinical use of graphene technology. Here, we demonstrate that our wafer-scalable GFETs array platform enables meaningful clinical results. As a case study of high clinical relevance, we demonstrate an accurate and robust portable GFET array biosensor platform for the detection of pancreatic ductal adenocarcinoma (PDAC) in patients' plasma through specific exosomes (GPC-1 expression) within 45 min. In order to facilitate reproducible detection in blood plasma, we optimized the analytical performance of GFET biosensors via the application of an internal control channel and the development of an optimized test protocol. Based on samples from 18 PDAC patients and 8 healthy controls, the GFET biosensor arrays could accurately discriminate between the two groups while being able to detect early cancer stages including stages 1 and 2. Furthermore, we confirmed the higher expression of GPC-1 and found that the concentration in PDAC plasma was on average more than 1 order of magnitude higher than in healthy samples. We found that these characteristics of GPC-1 cancerous exosomes are responsible for an increase in the number of target exosomes on the surface of graphene, leading to an improved signal response of the GFET biosensors. This GFET biosensor platform holds great promise for the development of an accurate tool for the rapid diagnosis of pancreatic cancer.
  5. Fulltext Asian-Pacific clinical practice guidelines on the management of hepatitis B: a 2015 update
    Sarin SK, Kumar M, Lau GK, Abbas Z, Chan HL, Chen CJ, et al.
    Hepatol Int, 2016 Jan;10(1):1-98.
    PMID: 26563120 DOI: 10.1007/s12072-015-9675-4
    Worldwide, some 240 million people have chronic hepatitis B virus (HBV), with the highest rates of infection in Africa and Asia. Our understanding of the natural history of HBV infection and the potential for therapy of the resultant disease is continuously improving. New data have become available since the previous APASL guidelines for management of HBV infection were published in 2012. The objective of this manuscript is to update the recommendations for the optimal management of chronic HBV infection. The 2015 guidelines were developed by a panel of Asian experts chosen by the APASL. The clinical practice guidelines are based on evidence from existing publications or, if evidence was unavailable, on the experts' personal experience and opinion after deliberations. Manuscripts and abstracts of important meetings published through January 2015 have been evaluated. This guideline covers the full spectrum of care of patients infected with hepatitis B, including new terminology, natural history, screening, vaccination, counseling, diagnosis, assessment of the stage of liver disease, the indications, timing, choice and duration of single or combination of antiviral drugs, screening for HCC, management in special situations like childhood, pregnancy, coinfections, renal impairment and pre- and post-liver transplant, and policy guidelines. However, areas of uncertainty still exist, and clinicians, patients, and public health authorities must therefore continue to make choices on the basis of the evolving evidence. The final clinical practice guidelines and recommendations are presented here, along with the relevant background information.
  6. Fulltext Integrating circulating T follicular memory cells and autoantibody repertoires for characterization of autoimmune disorders
    Harris EM, Chamseddine S, Chu A, Senkpeil L, Nikiciuk M, Al-Musa A, et al.
    medRxiv, 2024 Mar 07.
    PMID: 38464255 DOI: 10.1101/2024.02.25.24303331
    INTRODUCTION: Autoimmune diseases are heterogeneous and often lack specific or sensitive diagnostic tests. Increased percentages of CD4+CXCR5+PD1+ circulating T follicular helper (cTfh) cells and skewed distributions of cTfh subtypes have been associated with autoimmunity. However, cTfh cell percentages can normalize with immunomodulatory treatment despite persistent disease activity, indicating the need for identifying additional cellular and/or serologic features correlating with autoimmunity.

    METHODS: The cohort included 50 controls and 56 patients with autoimmune cytopenias, gastrointestinal, pulmonary, and/or neurologic autoimmune disease. Flow cytometry was used to measure CD4+CXCR5+ T cell subsets expressing the chemokine receptors CXCR3 and/or CCR6: CXCR3+CCR6- Type 1, CXCR3-CCR6- Type 2, CXCR3+CCR6+ Type 1/17, and CXCR3- CCR6+ Type 17 T cells. IgG and IgA autoantibodies were quantified using a microarray featuring 1616 full-length, conformationally intact protein antigens. The 97.5th percentile in the control cohort defined normal limits for T cell subset percentages and total number (burden) of autoantibodies.

    RESULTS: This study focused on CD4+CXCR5+ T cells because CXCR5 upregulation occurs after cognate T-B cell interactions characteristic of autoimmune diseases. We refer to these cells as circulating T follicular memory (cTfm) cells to acknowledge the dynamic nature of antigen-experienced CXCR5+ T cells, which encompass progenitors of cTfh or Tfh cells as well as early effector memory T cells that have not yet lost CXCR5. Compared to controls, 57.1% of patients had increased CXCR5+CXCR3+CCR6+ cTfm1/17 and 25% had increased CXCR5+CXCR3-CCR6+ cTfm17 cell percentages. Patients had significantly more diverse IgG and IgA autoantibodies than controls and 44.6% had an increased burden of autoantibodies of either isotype. Unsupervised autoantibody clustering identified three clusters of patients with IgG autoantibody profiles distinct from those of controls, enriched for patients with active autoimmunity and monogenic diseases. An increased percentage of cTfm17 cells was most closely associated with an increased burden of high-titer IgG and IgA autoantibodies. A composite measure integrating increased cTfm1/17, cTfm17, and high-titer IgG and/or IgA autoantibodies had 91.1% sensitivity and 90.9% specificity for identifying patients with autoimmunity. Percentages of cTfm1/17 and cTfm17 percentages and numbers of high-titer autoantibodies in patients receiving immunomodulatory treatment did not differ from those in untreated patients, thus suggesting that measurements of cTfm can complement measurements of other cellular markers affected by treatment.

    CONCLUSIONS: This study highlights two new approaches for assessing autoimmunity: measuring CD4+CXCR5+ cTfm subsets as well as total burden of autoantibodies. Our findings suggest that these approaches are particularly relevant to patients with rare autoimmune disorders for whom target antigens and prognosis are often unknown.

  7. Rate of tree carbon accumulation increases continuously with tree size
    Stephenson NL, Das AJ, Condit R, Russo SE, Baker PJ, Beckman NG, et al.
    Nature, 2014 Mar 6;507(7490):90-3.
    PMID: 24429523 DOI: 10.1038/nature12914
    Forests are major components of the global carbon cycle, providing substantial feedback to atmospheric greenhouse gas concentrations. Our ability to understand and predict changes in the forest carbon cycle--particularly net primary productivity and carbon storage--increasingly relies on models that represent biological processes across several scales of biological organization, from tree leaves to forest stands. Yet, despite advances in our understanding of productivity at the scales of leaves and stands, no consensus exists about the nature of productivity at the scale of the individual tree, in part because we lack a broad empirical assessment of whether rates of absolute tree mass growth (and thus carbon accumulation) decrease, remain constant, or increase as trees increase in size and age. Here we present a global analysis of 403 tropical and temperate tree species, showing that for most species mass growth rate increases continuously with tree size. Thus, large, old trees do not act simply as senescent carbon reservoirs but actively fix large amounts of carbon compared to smaller trees; at the extreme, a single big tree can add the same amount of carbon to the forest within a year as is contained in an entire mid-sized tree. The apparent paradoxes of individual tree growth increasing with tree size despite declining leaf-level and stand-level productivity can be explained, respectively, by increases in a tree's total leaf area that outpace declines in productivity per unit of leaf area and, among other factors, age-related reductions in population density. Our results resolve conflicting assumptions about the nature of tree growth, inform efforts to undertand and model forest carbon dynamics, and have additional implications for theories of resource allocation and plant senescence.
  8. Fulltext Erratum: Publisher Correction: Homologous recombination DNA repair defects in PALB2-associated breast cancers
    Li A, Geyer FC, Blecua P, Lee JY, Selenica P, Brown DN, et al.
    NPJ Breast Cancer, 2019 11 19;5:44.
    PMID: 31754629 DOI: 10.1038/s41523-019-0140-8
    [This corrects the article DOI: 10.1038/s41523-019-0115-9.].
  9. Fulltext Cholera prevention and control in Asian countries
    Ahmed MU, Baquilod M, Deola C, Tu ND, Anh DD, Grasso C, et al.
    BMC Proc, 2018;12(Suppl 13):62.
    PMID: 30807619 DOI: 10.1186/s12919-018-0158-1
    Cholera remains a major public health problem in many countries. Poor sanitation and inappropriate clean water supply, insufficient health literacy and community mobilization, absence of national plans and cross-border collaborations are major factors impeding optimal control of cholera in endemic countries. In March 2017, a group of experts from 10 Asian cholera-prone countries that belong to the Initiative against Diarrheal and Enteric Diseases in Africa and Asia (IDEA), together with representatives from the World Health Organization, the US National Institutes of Health, International Vaccine Institute, Agence de médecine préventive, NGOs (Save the Children) and UNICEF, met in Hanoi (Vietnam) to share progress in terms of prevention and control interventions on water, sanitation and hygiene (WASH), surveillance and oral cholera vaccine use. This paper reports on the country situation, gaps identified in terms of cholera prevention and control and strategic interventions to bridge these gaps.
  10. Fulltext Impact of mediterranean diet promotion on environmental sustainability: a longitudinal analysis
    Álvarez-Álvarez L, Vitelli-Storelli F, Rubín-García M, García S, Bouzas C, Ruíz-Canela M, et al.
    Public Health, 2024 May;230:12-20.
    PMID: 38479163 DOI: 10.1016/j.puhe.2024.02.010
    OBJECTIVE: This article aims to estimate the differences in environmental impact (greenhouse gas [GHG] emissions, land use, energy used, acidification and potential eutrophication) after one year of promoting a Mediterranean diet (MD).

    METHODS: Baseline and 1-year follow-up data from 5800 participants in the PREDIMED-Plus study were used. Each participant's food intake was estimated using validated semi-quantitative food frequency questionnaires, and the adherence to MD using the Dietary Score. The influence of diet on environmental impact was assessed through the EAT-Lancet Commission tables. The influence of diet on environmental impact was assessed through the EAT-Lancet Commission tables. The association between MD adherence and its environmental impact was calculated using adjusted multivariate linear regression models.

    RESULTS: After one year of intervention, the kcal/day consumed was significantly reduced (-125,1 kcal/day), adherence to a MD pattern was improved (+0,9) and the environmental impact due to the diet was significantly reduced (GHG: -361 g/CO2-eq; Acidification:-11,5 g SO2-eq; Eutrophication:-4,7 g PO4-eq; Energy use:-842,7 kJ; and Land use:-2,2 m2). Higher adherence to MD (high vs. low) was significantly associated with lower environmental impact both at baseline and one year follow-up. Meat products had the greatest environmental impact in all the factors analysed, both at baseline and at one-year follow-up, in spite of the reduction observed in their consumption.

    CONCLUSIONS: A program promoting a MD, after one year of intervention, significantly reduced the environmental impact in all the factors analysed. Meat products had the greatest environmental impact in all the dimensions analysed.

  11. Fulltext Homologous recombination DNA repair defects in PALB2-associated breast cancers
    Li A, Geyer FC, Blecua P, Lee JY, Selenica P, Brown DN, et al.
    NPJ Breast Cancer, 2019;5:23.
    PMID: 31428676 DOI: 10.1038/s41523-019-0115-9
    Mono-allelic germline pathogenic variants in the Partner And Localizer of BRCA2 (PALB2) gene predispose to a high-risk of breast cancer development, consistent with the role of PALB2 in homologous recombination (HR) DNA repair. Here, we sought to define the repertoire of somatic genetic alterations in PALB2-associated breast cancers (BCs), and whether PALB2-associated BCs display bi-allelic inactivation of PALB2 and/or genomic features of HR-deficiency (HRD). Twenty-four breast cancer patients with pathogenic PALB2 germline mutations were analyzed by whole-exome sequencing (WES, n = 16) or targeted capture massively parallel sequencing (410 cancer genes, n = 8). Somatic genetic alterations, loss of heterozygosity (LOH) of the PALB2 wild-type allele, large-scale state transitions (LSTs) and mutational signatures were defined. PALB2-associated BCs were found to be heterogeneous at the genetic level, with PIK3CA (29%), PALB2 (21%), TP53 (21%), and NOTCH3 (17%) being the genes most frequently affected by somatic mutations. Bi-allelic PALB2 inactivation was found in 16 of the 24 cases (67%), either through LOH (n = 11) or second somatic mutations (n = 5) of the wild-type allele. High LST scores were found in all 12 PALB2-associated BCs with bi-allelic PALB2 inactivation sequenced by WES, of which eight displayed the HRD-related mutational signature 3. In addition, bi-allelic inactivation of PALB2 was significantly associated with high LST scores. Our findings suggest that the identification of bi-allelic PALB2 inactivation in PALB2-associated BCs is required for the personalization of HR-directed therapies, such as platinum salts and/or PARP inhibitors, as the vast majority of PALB2-associated BCs without PALB2 bi-allelic inactivation lack genomic features of HRD.
  12. Fulltext Erratum to: The management of intra-abdominal infections from a global perspective: 2017 WSES guidelines for management of intra-abdominal infections
    Sartelli M, Chichom-Mefire A, Labricciosa FM, Hardcastle T, Abu-Zidan FM, Adesunkanmi AK, et al.
    World J Emerg Surg, 2017;12:36.
    PMID: 28785302 DOI: 10.1186/s13017-017-0148-z
    [This corrects the article DOI: 10.1186/s13017-017-0141-6.].
  13. Global cross-cultural validation of a brief measure for identifying potential suicide risk in 42 countries
    Gewirtz-Meydan A, Koós M, Nagy L, Kraus SW, Demetrovics Z, Potenza MN, et al.
    Public Health, 2024 Apr;229:13-23.
    PMID: 38382177 DOI: 10.1016/j.puhe.2023.12.031
    OBJECTIVES: This study aimed to examine the psychometric properties of the P4 suicide screener in a multinational sample. The primary goal was to evaluate the reliability and validity of the scale and investigate its convergent validity by analyzing its correlation with depression, anxiety, and substance use.

    STUDY DESIGN: The study design is a cross-sectional self-report study conducted across 42 countries.

    METHODS: A cross-sectional, self-report study was conducted in 42 countries, with a total of 82,243 participants included in the final data set.

    RESULTS: The study provides an overview of suicide ideation rates across 42 countries and confirms the structural validity of the P4 screener. The findings indicated that sexual and gender minority individuals exhibited higher rates of suicidal ideation. The P4 screener showed adequate reliability, convergence, and discriminant validity, and a cutoff score of 1 is recommended to identify individuals at risk of suicidal behavior.

    CONCLUSIONS: The study supports the reliability and validity of the P4 suicide screener across 42 diverse countries, highlighting the importance of using a cross-cultural suicide risk assessment to standardize the identification of high-risk individuals and tailoring culturally sensitive suicide prevention strategies.

  14. Fulltext What information and the extent of information research participants need in informed consent forms: a multi-country survey
    Karbwang J, Koonrungsesomboon N, Torres CE, Jimenez EB, Kaur G, Mathur R, et al.
    BMC Med Ethics, 2018 09 15;19(1):79.
    PMID: 30219106 DOI: 10.1186/s12910-018-0318-x
    BACKGROUND: The use of lengthy, detailed, and complex informed consent forms (ICFs) is of paramount concern in biomedical research as it may not truly promote the rights and interests of research participants. The extent of information in ICFs has been the subject of debates for decades; however, no clear guidance is given. Thus, the objective of this study was to determine the perspectives of research participants about the type and extent of information they need when they are invited to participate in biomedical research.

    METHODS: This multi-center, cross-sectional, descriptive survey was conducted at 54 study sites in seven Asia-Pacific countries. A modified Likert-scale questionnaire was used to determine the importance of each element in the ICF among research participants of a biomedical study, with an anchored rating scale from 1 (not important) to 5 (very important).

    RESULTS: Of the 2484 questionnaires distributed, 2113 (85.1%) were returned. The majority of respondents considered most elements required in the ICF to be 'moderately important' to 'very important' for their decision making (mean score, ranging from 3.58 to 4.47). Major foreseeable risk, direct benefit, and common adverse effects of the intervention were considered to be of most concerned elements in the ICF (mean score = 4.47, 4.47, and 4.45, respectively).

    CONCLUSIONS: Research participants would like to be informed of the ICF elements required by ethical guidelines and regulations; however, the importance of each element varied, e.g., risk and benefit associated with research participants were considered to be more important than the general nature or technical details of research. Using a participant-oriented approach by providing more details of the participant-interested elements while avoiding unnecessarily lengthy details of other less important elements would enhance the quality of the ICF.

  15. Fulltext Clinical standards for the diagnosis and management of asthma in low- and middle-income countries
    Jayasooriya S, Stolbrink M, Khoo EM, Sunte IT, Awuru JI, Cohen M, et al.
    Int J Tuberc Lung Dis, 2023 Sep 01;27(9):658-667.
    PMID: 37608484 DOI: 10.5588/ijtld.23.0203
    BACKGROUND: The aim of these clinical standards is to aid the diagnosis and management of asthma in low-resource settings in low- and middle-income countries (LMICs).METHODS: A panel of 52 experts in the field of asthma in LMICs participated in a two-stage Delphi process to establish and reach a consensus on the clinical standards.RESULTS: Eighteen clinical standards were defined: Standard 1, Every individual with symptoms and signs compatible with asthma should undergo a clinical assessment; Standard 2, In individuals (>6 years) with a clinical assessment supportive of a diagnosis of asthma, a hand-held spirometry measurement should be used to confirm variable expiratory airflow limitation by demonstrating an acute response to a bronchodilator; Standard 3, Pre- and post-bronchodilator spirometry should be performed in individuals (>6 years) to support diagnosis before treatment is commenced if there is diagnostic uncertainty; Standard 4, Individuals with an acute exacerbation of asthma and clinical signs of hypoxaemia or increased work of breathing should be given supplementary oxygen to maintain saturation at 94-98%; Standard 5, Inhaled short-acting beta-2 agonists (SABAs) should be used as an emergency reliever in individuals with asthma via an appropriate spacer device for metered-dose inhalers; Standard 6, Short-course oral corticosteroids should be administered in appropriate doses to individuals having moderate to severe acute asthma exacerbations (minimum 3-5 days); Standard 7, Individuals having a severe asthma exacerbation should receive emergency care, including oxygen therapy, systemic corticosteroids, inhaled bronchodilators (e.g., salbutamol with or without ipratropium bromide) and a single dose of intravenous magnesium sulphate should be considered; Standard 8, All individuals with asthma should receive education about asthma and a personalised action plan; Standard 9, Inhaled medications (excluding dry-powder devices) should be administered via an appropriate spacer device in both adults and children. Children aged 0-3 years will require the spacer to be coupled to a face mask; Standard 10, Children aged <5 years with asthma should receive a SABA as-needed at step 1 and an inhaled corticosteroid (ICS) to cover periods of wheezing due to respiratory viral infections, and SABA as-needed and daily ICS from step 2 upwards; Standard 11, Children aged 6-11 years with asthma should receive an ICS taken whenever an inhaled SABA is used; Standard 12, All adolescents aged 12-18 years and adults with asthma should receive a combination inhaler (ICS and rapid onset of action long-acting beta-agonist [LABA] such as budesonide-formoterol), where available, to be used either as-needed (for mild asthma) or as both maintenance and reliever therapy, for moderate to severe asthma; Standard 13, Inhaled SABA alone for the management of patients aged >12 years is not recommended as it is associated with increased risk of morbidity and mortality. It should only be used where there is no access to ICS.The following standards (14-18) are for settings where there is no access to inhaled medicines. Standard 14, Patients without access to corticosteroids should be provided with a single short course of emergency oral prednisolone; Standard 15, Oral SABA for symptomatic relief should be used only if no inhaled SABA is available. Adjust to the individual's lowest beneficial dose to minimise adverse effects; Standard 16, Oral leukotriene receptor antagonists (LTRA) can be used as a preventive medication and is preferable to the use of long-term oral systemic corticosteroids; Standard 17, In exceptional circumstances, when there is a high risk of mortality from exacerbations, low-dose oral prednisolone daily or on alternate days may be considered on a case-by-case basis; Standard 18. Oral theophylline should be restricted for use in situations where it is the only bronchodilator treatment option available.CONCLUSION: These first consensus-based clinical standards for asthma management in LMICs are intended to help clinicians provide the most effective care for people in resource-limited settings.
  16. Fulltext Erratum to: Antimicrobials: a global alliance for optimizing their rational use in intra-abdominal infections (AGORA)
    Sartelli M, Weber DG, Ruppé E, Bassetti M, Wright BJ, Ansaloni L, et al.
    World J Emerg Surg, 2017;12:35.
    PMID: 28785301 DOI: 10.1186/s13017-017-0147-0
    [This corrects the article DOI: 10.1186/s13017-016-0089-y.].
  17. Observation of ϒ(2S)→γη_{b}(1S) Decay
    Fulsom BG, Pedlar TK, Adachi I, Aihara H, Al Said S, Asner DM, et al.
    Phys Rev Lett, 2018 Dec 07;121(23):232001.
    PMID: 30576207 DOI: 10.1103/PhysRevLett.121.232001
    We report the observation of ϒ(2S)→γη_{b}(1S) decay based on an analysis of the inclusive photon spectrum of 24.7  fb^{-1} of e^{+}e^{-} collisions at the ϒ(2S) center-of-mass energy collected with the Belle detector at the KEKB asymmetric-energy e^{+}e^{-} collider. We measure a branching fraction of B[ϒ(2S)→γη_{b}(1S)]=(6.1_{-0.7-0.6}^{+0.6+0.9})×10^{-4} and derive an η_{b}(1S) mass of 9394.8_{-3.1-2.7}^{+2.7+4.5}  MeV/c^{2}, where the uncertainties are statistical and systematic, respectively. The significance of our measurement is greater than 7 standard deviations, constituting the first observation of this decay mode.
  18. First Measurements of Absolute Branching Fractions of the Ξ_{c}^{0} Baryon at Belle
    Li YB, Shen CP, Yuan CZ, Adachi I, Aihara H, Al Said S, et al.
    Phys Rev Lett, 2019 Mar 01;122(8):082001.
    PMID: 30932568 DOI: 10.1103/PhysRevLett.122.082001
    We present the first measurements of absolute branching fractions of Ξ_{c}^{0} decays into Ξ^{-}π^{+}, ΛK^{-}π^{+}, and pK^{-}K^{-}π^{+} final states. The measurements are made using a dataset comprising (772±11)×10^{6} BB[over ¯] pairs collected at the ϒ(4S) resonance with the Belle detector at the KEKB e^{+}e^{-} collider. We first measure the absolute branching fraction for B^{-}→Λ[over ¯]_{c}^{-}Ξ_{c}^{0} using a missing-mass technique; the result is B(B^{-}→Λ[over ¯]_{c}^{-}Ξ_{c}^{0})=(9.51±2.10±0.88)×10^{-4}. We subsequently measure the product branching fractions B(B^{-}→Λ[over ¯]_{c}^{-}Ξ_{c}^{0})B(Ξ_{c}^{0}→Ξ^{-}π^{+}), B(B^{-}→Λ[over ¯]_{c}^{-}Ξ_{c}^{0})B(Ξ_{c}^{0}→ΛK^{-}π^{+}), and B(B^{-}→Λ[over ¯]_{c}^{-}Ξ_{c}^{0})B(Ξ_{c}^{0}→pK^{-}K^{-}π^{+}) with improved precision. Dividing these product branching fractions by the result for B^{-}→Λ[over ¯]_{c}^{-}Ξ_{c}^{0} yields the following branching fractions: B(Ξ_{c}^{0}→Ξ^{-}π^{+})=(1.80±0.50±0.14)%, B(Ξ_{c}^{0}→ΛK^{-}π^{+})=(1.17±0.37±0.09)%, and B(Ξ_{c}^{0}→pK^{-}K^{-}π^{+})=(0.58±0.23±0.05)%. For the above branching fractions, the first uncertainties are statistical and the second are systematic. Our result for B(Ξ_{c}^{0}→Ξ^{-}π^{+}) can be combined with Ξ_{c}^{0} branching fractions measured relative to Ξ_{c}^{0}→Ξ^{-}π^{+} to yield other absolute Ξ_{c}^{0} branching fractions.
  19. Search for B^{-}→μ^{-}ν[over ¯]_{μ} Decays at the Belle Experiment
    Sibidanov A, Varvell KE, Adachi I, Aihara H, Al Said S, Asner DM, et al.
    Phys Rev Lett, 2018 Jul 20;121(3):031801.
    PMID: 30085771 DOI: 10.1103/PhysRevLett.121.031801
    We report the results of a search for the rare, purely leptonic decay B^{-}→μ^{-}ν[over ¯]_{μ} performed with a 711  fb^{-1} data sample that contains 772×10^{6}  BB[over ¯] pairs, collected near the ϒ(4S) resonance with the Belle detector at the KEKB asymmetric-energy e^{+}e^{-} collider. The signal events are selected based on the presence of a high momentum muon and the topology of the rest of the event showing properties of a generic B-meson decay, as well as the missing energy and momentum being consistent with the hypothesis of a neutrino from the signal decay. We find a 2.4 standard deviation excess above background including systematic uncertainties, which corresponds to a branching fraction of B(B^{-}→μ^{-}ν[over ¯]_{μ})=(6.46±2.22±1.60)×10^{-7} or a frequentist 90% confidence level interval on the B^{-}→μ^{-}ν[over ¯]_{μ} branching fraction of [2.9,10.7]×10^{-7}.
  20. Observation of ϒ(4S)→η^{'}ϒ(1S)
    Guido E, Mussa R, Tamponi U, Aihara H, Al Said S, Asner DM, et al.
    Phys Rev Lett, 2018 Aug 10;121(6):062001.
    PMID: 30141661 DOI: 10.1103/PhysRevLett.121.062001
    We report the first observation of the hadronic transition ϒ(4S)→η^{'}ϒ(1S), using 496  fb^{-1} data collected at the ϒ(4S) resonance with the Belle detector at the KEKB asymmetric-energy e^{+}e^{-} collider. We reconstruct the η^{'} meson through its decays to ρ^{0}γ and to π^{+}π^{-}η, with η→γγ. We measure B(ϒ(4S)→η^{'}ϒ(1S))=[3.43±0.88(stat)±0.21(syst)]×10^{-5}, with a significance of 5.7σ.
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