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BACKGROUND: Exposure to high doses of ionizing radiation is among the few well-established brain tumour risk factors. We used data from the Interphone study to evaluate the effects of exposure to low-dose radiation from diagnostic radiological examinations on glioma, meningioma and acoustic neuroma risk. METHODS: Brain tumour cases (2644 gliomas, 2236 meningiomas, 1083 neuromas) diagnosed in 2000-02 were identified through hospitals in 13 countries, and 6068 controls (population-based controls in most centres) were included in the analysis. Participation across all centres was 64% for glioma cases, 78% for meningioma cases, 82% for acoustic neuroma cases and 53% for controls. Information on previous diagnostic radiological examinations was obtained by interviews, including the frequency, timing and indication for the examinations. Typical brain doses per type of examination were estimated based on the literature. Examinations within the 5 years before the index date were excluded from the dose estimation. Adjusted odds ratios were estimated using conditional logistic regression. RESULTS: No materially or consistently increased odds ratios for glioma, meningioma or acoustic neuroma were found for any specific type of examination, including computed tomography of the head and cerebral angiography. The only indication of an elevated risk was an increasing trend in risk of meningioma with the number of isotope scans, but no such trends for other examinations were observed. No gradient was found in risk with estimated brain dose. Age at exposure did not substantially modify the findings. Sensitivity analyses gave results consistent with the main analysis. CONCLUSIONS: There was no consistent evidence for increased risks of brain tumours with X-ray examinations, although error from selection and recall bias cannot be completely excluded. A cautious interpretation is warranted for the observed association between isotope scans and meningioma.

AIM: Following the establishment of paediatric palliative care services over recent decades, this study sought to identify information to inform future policy and practice. METHODS: A rapid review using thematic synthesis was conducted to synthesise existing information about improving paediatric palliative care. Information was extracted in relation to key areas for investment and change: quality, access, advance care planning, skills, research, collaboration and community awareness. RESULTS: A total of 2228 literature sources were screened, with 369 included. Synthesised information identified clear ways to improve quality of care, access to care, advance care planning, and research and data collection. The synthesis identified knowledge gaps in understanding how to improve skills in paediatric palliative care, collaboration across Australian jurisdictions and community awareness. CONCLUSIONS: The findings of this review bring together information from a vast range of sources to provide action-oriented information to target investment and change in paediatric palliative care over the coming decades.

Over the last ten years there has been a large increase in the number of projects using sound to represent astronomical data and concepts. Motivation for these projects includes the potential to enhance scientific discovery within complex datasets, by utilising the inherent multi-dimensionality of sound and the ability of our hearing to filter signals from noise. Other motivations include creating engaging multi-sensory resources, for education and public engagement, and making astronomy more accessible to people who are blind or have low vision, promoting their participation in science and related careers. We describe potential benefits of sound within these contexts and provide an overview of the nearly 100 sound-based astronomy projects that we identified. We discuss current limitations and challenges of the approaches taken. Finally, we suggest future directions to help realise the full potential of sound-based techniques in general and to widen their application within the astronomy community., Comment: Accepted for publication in Nature Astronomy. A Word document (more accessible with screen readers) is available under 'ancillary files'. This is the author's own version (it is not the Version of Record and does not reflect post-acceptance improvements, or any corrections). The Version of Record will be available with doi: 10.1038/s41550-022-01721-z

AIM: Following the establishment of paediatric palliative care services over recent decades, this study sought to identify information to inform future policy and practice. METHODS: A rapid review using thematic synthesis was conducted to synthesise existing information about improving paediatric palliative care. Information was extracted in relation to key areas for investment and change: quality, access, advance care planning, skills, research, collaboration and community awareness. RESULTS: A total of 2228 literature sources were screened, with 369 included. Synthesised information identified clear ways to improve quality of care, access to care, advance care planning, and research and data collection. The synthesis identified knowledge gaps in understanding how to improve skills in paediatric palliative care, collaboration across Australian jurisdictions and community awareness. CONCLUSIONS: The findings of this review bring together information from a vast range of sources to provide action-oriented information to target investment and change in paediatric palliative care over the coming decades.

Background: Measurable residual disease (MRD) monitoring in acute lymphoblastic leukemia (ALL) is an important predictive factor for patient outcome and treatment intensification. Molecular monitoring, particularly with quantitative polymerase chain reaction (qPCR) to measure immunoglobin heavy or kappa chain (Ig) or T-cell receptor (TCR) gene rearrangements, offers high sensitivity but accessibility is limited by expertise, cost, and turnaround time. Flow cytometric assays are cheaper and more widely available, and sensitivity is improved with multi-parameter flow cytometry at eight or more colors. Method(s): We developed a 10-color single tube flow cytometry assay. Samples were subject to bulk ammonium chloride lysis to maximize cell yields with a target of 1 x 106 events. Once normal maturation patterns were established, patient samples were analyzed in parallel to standard molecular monitoring. Result(s): Flow cytometry was performed on 114 samples. An informative immunophenotype was identifiable in all 22 patients who had a diagnostic sample. MRD analysis was performed on 87 samples. The median lower limits of detection and quantification were 0.004% (range 0.0005%-0.028%) and 0.01% (range 0.001%-0.07%) respectively. Sixty-five samples had concurrent molecular MRD testing, with good correlation (r = 0.83, p < 0.001). Results were concordant in 52 samples, and discordant in 13 samples, including one case where impending relapse was detected by flow cytometry but not Ig/TCR qPCR. Conclusion(s): Our 10-color flow cytometric MRD assay provided adequate sensitivity and good correlation with molecular assays. This technique offers rapid and affordable testing in B-ALL patients, including cases where a suitable molecular assay cannot be developed or has reduced sensitivity.Copyright © 2021 International Clinical Cytometry Society.

Background: Measurable residual disease (MRD) monitoring in acute lymphoblastic leukemia (ALL) is an important predictive factor for patient outcome and treatment intensification. Molecular monitoring, particularly with quantitative polymerase chain reaction (qPCR) to measure immunoglobin heavy or kappa chain (Ig) or T-cell receptor (TCR) gene rearrangements, offers high sensitivity but accessibility is limited by expertise, cost, and turnaround time. Flow cytometric assays are cheaper and more widely available, and sensitivity is improved with multi-parameter flow cytometry at eight or more colors. Method(s): We developed a 10-color single tube flow cytometry assay. Samples were subject to bulk ammonium chloride lysis to maximize cell yields with a target of 1 x 106 events. Once normal maturation patterns were established, patient samples were analyzed in parallel to standard molecular monitoring. Result(s): Flow cytometry was performed on 114 samples. An informative immunophenotype was identifiable in all 22 patients who had a diagnostic sample. MRD analysis was performed on 87 samples. The median lower limits of detection and quantification were 0.004% (range 0.0005%-0.028%) and 0.01% (range 0.001%-0.07%) respectively. Sixty-five samples had concurrent molecular MRD testing, with good correlation (r = 0.83, p < 0.001). Results were concordant in 52 samples, and discordant in 13 samples, including one case where impending relapse was detected by flow cytometry but not Ig/TCR qPCR. Conclusion(s): Our 10-color flow cytometric MRD assay provided adequate sensitivity and good correlation with molecular assays. This technique offers rapid and affordable testing in B-ALL patients, including cases where a suitable molecular assay cannot be developed or has reduced sensitivity.Copyright © 2021 International Clinical Cytometry Society.

BACKGROUND: There is a lack of information regarding the provision of parental leave for surgical careers. This survey study aims to evaluate the experience of maternity/paternity leave and views on work-life balance globally.METHODS: A 55-item online survey in 24 languages was distributed via social media as per CHERRIES guideline from February to March 2020. It explored parental leave entitlements, attitude towards leave taking, financial impact, time spent with children and compatibility of parenthood with surgical career.RESULTS: Of the 1393 (male : female, 514 : 829) respondents from 65 countries, there were 479 medical students, 349 surgical trainees and 513 consultants. Consultants had less than the recommended duration of maternity leave (43.8 versus 29.1 per cent), no paid maternity (8.3 versus 3.2 per cent) or paternity leave (19.3 versus 11.0 per cent) compared with trainees. Females were less likely to have children than males (36.8 versus 45.6 per cent, P = 0.010) and were more often told surgery is incompatible with parenthood (80.2 versus 59.5 per cent, P < 0.001). Males spent less than 20 per cent of their salary on childcare and fewer than 30 hours/week with their children. More than half (59.2 per cent) of medical students did not believe a surgical career allowed work-life balance.CONCLUSION: Surgeons across the globe had inadequate parental leave. Significant gender disparity was seen in multiple aspects.

BACKGROUND: Measurable residual disease (MRD) monitoring in acute lymphoblastic leukemia (ALL) is an important predictive factor for patient outcome and treatment intensification. Molecular monitoring, particularly with quantitative polymerase chain reaction (qPCR) to measure immunoglobin heavy or kappa chain (Ig) or T-cell receptor (TCR) gene rearrangements, offers high sensitivity but accessibility is limited by expertise, cost, and turnaround time. Flow cytometric assays are cheaper and more widely available, and sensitivity is improved with multi-parameter flow cytometry at eight or more colors. METHODS: We developed a 10-color single tube flow cytometry assay. Samples were subject to bulk ammonium chloride lysis to maximize cell yields with a target of 1 × 106 events. Once normal maturation patterns were established, patient samples were analyzed in parallel to standard molecular monitoring. RESULTS: Flow cytometry was performed on 114 samples. An informative immunophenotype was identifiable in all 22 patients who had a diagnostic sample. MRD analysis was performed on 87 samples. The median lower limits of detection and quantification were 0.004% (range 0.0005%-0.028%) and 0.01% (range 0.001%-0.07%) respectively. Sixty-five samples had concurrent molecular MRD testing, with good correlation (r = 0.83, p < 0.001). Results were concordant in 52 samples, and discordant in 13 samples, including one case where impending relapse was detected by flow cytometry but not Ig/TCR qPCR. CONCLUSIONS: Our 10-color flow cytometric MRD assay provided adequate sensitivity and good correlation with molecular assays. This technique offers rapid and affordable testing in B-ALL patients, including cases where a suitable molecular assay cannot be developed or has reduced sensitivity.

AIM: Following the establishment of paediatric palliative care services over recent decades, this study sought to identify information to inform future policy and practice. METHODS: A rapid review using thematic synthesis was conducted to synthesise existing information about improving paediatric palliative care. Information was extracted in relation to key areas for investment and change: quality, access, advance care planning, skills, research, collaboration and community awareness. RESULTS: A total of 2228 literature sources were screened, with 369 included. Synthesised information identified clear ways to improve quality of care, access to care, advance care planning, and research and data collection. The synthesis identified knowledge gaps in understanding how to improve skills in paediatric palliative care, collaboration across Australian jurisdictions and community awareness. CONCLUSIONS: The findings of this review bring together information from a vast range of sources to provide action-oriented information to target investment and change in paediatric palliative care over the coming decades.

Antifungal prophylaxis can reduce morbidity and mortality from invasive fungal disease (IFD). However, its use needs to be optimised and appropriately targeted to patients at highest risk to derive the most benefit. In addition to established risks for IFD, considerable recent progress in the treatment of malignancies has resulted in the development of new 'at-risk' groups. The changing epidemiology of IFD and emergence of drug resistance continue to impact choice of prophylaxis, highlighting the importance of active surveillance and knowledge of local epidemiology. These guidelines aim to highlight emerging risk groups and review the evidence and limitations around new formulations of established agents and new antifungal drugs. It provides recommendations around use and choice of antifungal prophylaxis, discusses the potential impact of the changing epidemiology of IFD and emergence of drug resistance, and future directions for risk stratification to assist optimal management of highly vulnerable patients.

BACKGROUND: There is a lack of information regarding the provision of parental leave for surgical careers. This survey study aims to evaluate the experience of maternity/paternity leave and views on work-life balance globally.METHODS: A 55-item online survey in 24 languages was distributed via social media as per CHERRIES guideline from February to March 2020. It explored parental leave entitlements, attitude towards leave taking, financial impact, time spent with children and compatibility of parenthood with surgical career.RESULTS: Of the 1393 (male : female, 514 : 829) respondents from 65 countries, there were 479 medical students, 349 surgical trainees and 513 consultants. Consultants had less than the recommended duration of maternity leave (43.8 versus 29.1 per cent), no paid maternity (8.3 versus 3.2 per cent) or paternity leave (19.3 versus 11.0 per cent) compared with trainees. Females were less likely to have children than males (36.8 versus 45.6 per cent, P = 0.010) and were more often told surgery is incompatible with parenthood (80.2 versus 59.5 per cent, P < 0.001). Males spent less than 20 per cent of their salary on childcare and fewer than 30 hours/week with their children. More than half (59.2 per cent) of medical students did not believe a surgical career allowed work-life balance.CONCLUSION: Surgeons across the globe had inadequate parental leave. Significant gender disparity was seen in multiple aspects.

Dasatinib has shown superiority over imatinib in achieving molecular responses (MRs) in chronic phase chronic myeloid leukemia but with a different toxicity profile, which may impact its overall benefit. Reported toxicities include pleural effusions and pulmonary hypertension, and although the incidence of these events is well described, response to therapy and impact of dose modifications on toxicity has not been comprehensively characterized in a real-world setting. We retrospectively reviewed the incidence of dasatinib adverse events in 212 chronic phase chronic myeloid leukemia patients at 17 Australian institutions. Adverse events were reported in 116 patients (55%), most commonly pleural effusions (53 patients, 25%), which was the predominant cause of permanent drug cessation. Age and dose were risk factors for pleural effusion (P < .01 and .047, respectively). Recurrence rates were higher in those who remained on 100 mg compared with those who dose reduced (P = .041); however, recurrence still occurred at 50 mg. Patients who developed pleural effusions were more likely to have achieved MR4.5 after 6 months of dasatinib than those without effusions (P = .008). Pulmonary hypertension occurred in 5% of patients, frequently in association with pleural effusion, and was reversible upon dasatinib cessation in 6 of 7 patients. Dose reductions and temporary cessations had minimal impact on MR rates. Our observations suggest that by using the lowest effective dose in older patients to minimize the effusion risk, dose modification for cytopenias, and care with concomitant antiplatelet therapy, the necessity for permanent dasatinib cessation due to toxicity is likely to be minimal in immunologically competent patients.

Dasatinib has shown superiority over imatinib in achieving molecular responses (MRs) in chronic phase chronic myeloid leukemia but with a different toxicity profile, which may impact its overall benefit. Reported toxicities include pleural effusions and pulmonary hypertension, and although the incidence of these events is well described, response to therapy and impact of dose modifications on toxicity has not been comprehensively characterized in a real-world setting. We retrospectively reviewed the incidence of dasatinib adverse events in 212 chronic phase chronic myeloid leukemia patients at 17 Australian institutions. Adverse events were reported in 116 patients (55%), most commonly pleural effusions (53 patients, 25%), which was the predominant cause of permanent drug cessation. Age and dose were risk factors for pleural effusion (P < .01 and .047, respectively). Recurrence rates were higher in those who remained on 100 mg compared with those who dose reduced (P = .041); however, recurrence still occurred at 50 mg. Patients who developed pleural effusions were more likely to have achieved MR4.5 after 6 months of dasatinib than those without effusions (P = .008). Pulmonary hypertension occurred in 5% of patients, frequently in association with pleural effusion, and was reversible upon dasatinib cessation in 6 of 7 patients. Dose reductions and temporary cessations had minimal impact on MR rates. Our observations suggest that by using the lowest effective dose in older patients to minimize the effusion risk, dose modification for cytopenias, and care with concomitant antiplatelet therapy, the necessity for permanent dasatinib cessation due to toxicity is likely to be minimal in immunologically competent patients.

BACKGROUND: The social, contextual, and behavioral determinants that influence care in patients at risk for invasive fungal diseases (IFD) are poorly understood. This knowledge gap is a barrier to the implementation of emerging antifungal stewardship (AFS) programs. We aimed to understand the barriers and enablers to AFS, opportunities for improvement, and perspectives of AFS for hematology patients at a major medical center in Australia. METHODS: Semistructured, face-to-face interviews were conducted with 35 clinicians from 6 specialties (hematology, infectious diseases, pharmacy, nursing, radiology, respiratory), followed by thematic analysis mapped to a behavioral change framework. RESULTS: Access to fungal diagnostics including bronchoscopy was identified as the key barrier to rational prescribing. Collective decision making was the norm, aided by an embedded stewardship model with on-demand access to infectious diseases expertise. Poor self-efficacy/knowledge among prescribers was actually an enabler of AFS, because clinicians willingly deferred to infectious diseases for advice. A growing outpatient population characterized by frequent care transitions was seen as an opportunity for AFS but neglected by an inpatient focused model, as was keeping pace with emerging fungal risks. Ad hoc surveillance, audit, and feedback practices frustrated population-level quality improvement for all actors. Antifungal stewardship was perceived as a specialized area that should be integrated within antimicrobial stewardship but aligned with the cultural expectations of hematologists. CONCLUSIONS: Antifungal stewardship is multifaceted, with fungal diagnostics a critical gap and outpatients a neglected area. Formal surveillance, audit, and feedback mechanisms are essential for population-level quality improvement. Resourcing is the next challenge because complex immunocompromised patients require personalized attention and audit of clinical outcomes including IFD is difficult.

Improving survival outcomes in adult B-cell acute lymphoblastic leukemia (B-ALL) remains a clinical challenge. Relapsed disease has a poor prognosis despite the use of tyrosine kinase inhibitors (TKIs) for Philadelphia chromosome positive (Ph+ ALL) cases and immunotherapeutic approaches, including blinatumomab and chimeric antigen receptor T cells. Targeting aberrant cell survival pathways with selective small molecule BH3-mimetic inhibitors of BCL-2 (venetoclax, S55746), BCL-XL (A1331852), or MCL1 (S63845) is an emerging therapeutic option. We report that combined targeting of BCL-2 and MCL1 is synergistic in B-ALL in vitro. The combination demonstrated greater efficacy than standard chemotherapeutics and TKIs in primary samples from adult B-ALL with Ph+ ALL, Ph-like ALL, and other B-ALL. Moreover, combined BCL-2 or MCL1 inhibition with dasatinib showed potent killing in primary Ph+ B-ALL cases, but the BH3-mimetic combination appeared superior in vitro in a variety of Ph-like ALL samples. In PDX models, combined BCL-2 and MCL1 targeting eradicated ALL from Ph- and Ph+ B-ALL cases, although fatal tumor lysis was observed in some instances of high tumor burden. We conclude that a dual BH3-mimetic approach is highly effective in diverse models of high-risk human B-ALL and warrants assessment in clinical trials that incorporate tumor lysis precautions.

We discuss shallow resonances in the nonrelativistic scattering of two particles using an effective field theory (EFT) that includes an auxiliary field with the quantum numbers of the resonance. We construct the manifestly renormalized scattering amplitude up to next-to-leading order in a systematic expansion. For a narrow resonance, the amplitude is perturbative except in the immediate vicinity of the resonance poles. It naturally has a zero in the low-energy region, analogous to the Ramsauer-Townsend effect. For a broad resonance, the leading-order amplitude is nonperturbative almost everywhere in the regime of validity of the EFT. We regain the results of an EFT without the auxiliary field, which is equivalent to the effective-range expansion with large scattering length and effective range. We also consider an additional fine tuning leading to a low-energy amplitude zero even for a broad resonance. We show that in all cases the requirement of renormalizability when the auxiliary field is not a ghost ensures the resonance poles are in the lower half of the complex momentum plane, as expected by other arguments. The systematic character of the EFT expansion is exemplified with a toy model serving as underlying theory., Comment: 19 pages, 14 figures

Although second-generation tyrosine kinase inhibitors (TKIs) show superiority in achieving deep molecular responses in chronic myeloid leukemia in chronic phase (CML-CP) compared with imatinib, the differing adverse effect (AE) profiles need consideration when deciding the best drug for individual patients. Long-term data from randomized trials of nilotinib demonstrate an increased risk of vascular AEs (VAEs) compared with other TKIs, although the natural history of these events in response to dose modifications or cessation has not been fully characterized. We retrospectively reviewed the incidence of nilotinib-associated AEs in 220 patients with CML-CP at 17 Australian institutions. Overall, AEs of any grade were reported in 95 patients (43%) and prompted nilotinib cessation in 46 (21%). VAEs occurred in 26 patients (12%), with an incidence of 4.1 events per 100 patient-years. Multivariate analysis identified age (P 5 .022) and dyslipidemia (P 5 .007) as independent variables for their development. There was 1 fatal first VAE, whereas the remaining patients either continued nilotinib (14 patients) or stopped it immediately (11 patients). Recurrent VAEs were associated with ongoing therapy in 7 of 14 who continued (with 2 fatal VAEs) vs 1 of 11 who discontinued (P 5 .04). Nineteen of the 23 evaluable patients surviving a VAE ultimately stopped nilotinib, of whom 14 received an alternative TKI. Dose reduction or cessation because of VAEs did not adversely affect maintenance of major molecular response. These findings demonstrate that in contrast to other AEs, VAEs are ideally managed with nilotinib cessation because of the increased risk of additional events with its ongoing use.Copyright © 2019 by The American Society of Hematology.

OBJECTIVE: To evaluate the effects of drug interventions that may modify the progression of chronic kidney disease (CKD) in adults with CKD stages 3 and 4. DESIGN: Systematic review and meta-analysis. METHODS: Searching MEDLINE, EMBASE, Database of Abstracts of Reviews of Effects, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, International Clinical Trials Registry Platform, Health Technology Assessment, Science Citation Index, Social Sciences Citation Index, Conference Proceedings Citation Index and Clinical Trials Register, from March 1999 to July 2018, we identified randomised controlled trials (RCTs) of drugs for hypertension, lipid modification, glycaemic control and sodium bicarbonate, compared with placebo, no drug or a drug from another class, in ≥40 adults with CKD stages 3 and/or 4, with at least 2 years of follow-up and reporting renal function (primary outcome), proteinuria, adverse events, maintenance dialysis, transplantation, cardiovascular events, cardiovascular mortality or all-cause mortality. Two reviewers independently screened citations and extracted data. For continuous outcomes, we used the ratio of means (ROM) at the end of the trial in random-effects meta-analyses. We assessed methodological quality with the Cochrane Risk of Bias Tool and confidence in the evidence using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) framework. RESULTS: We included 35 RCTs and over 51 000 patients. Data were limited, and heterogeneity varied. Final renal function (estimated glomerular filtration rate) was 6% higher in those taking glycaemic control drugs (ROM 1.06, 95% CI 1.02 to 1.10, I2=0%, low GRADE confidence) and 4% higher in those taking lipid-modifying drugs (ROM 1.04, 95% CI 1.00 to 1.08, I2=88%, very low GRADE confidence). For RCTs of antihypertensive drugs, there were no significant differences in renal function. Treatment with lipid-modifying drugs led to a 36% reduction in c

AIMS The International Collaboration on Cancer Reporting (ICCR) has provided detailed datasets based upon the published reporting protocols of the Royal College of Pathologists, The Royal College of Pathologists of Australasia and the College of American Pathologists. METHODS AND RESULTS The dataset for carcinomas of renal tubular origin treated by nephrectomy was developed to provide a minimum structured reporting template suitable for international use and incorporated recommendations from the 2012 Vancouver Consensus Conference of the International Society of Urological Pathology and the fourth edition of the World Health Organization Bluebook on tumours of the urinary and male genital systems published in 2016. Reporting elements were divided into those, which are Required and Recommended components of the report. Required elements are; specimen laterality, operative procedure, attached structures, tumour focality, tumour dimension, tumour type, WHO/ISUP grade, sarcomatoid/rhabdoid morphology, tumour necrosis, extent of invasion, lymph node status, surgical margin status, AJCC TNM staging and co-existing pathology. Recommended reporting elements are; pre-operative treatment, details of tissue removed for experimental purposes prior to submission, site of tumour(s) block identification key, extent of sarcomatoid and/or rhabdoid component, extent of necrosis, presence of tumour in renal vein wall, lymphovascular invasion and lymph node status (size of largest focus and extranodal extension). CONCLUSIONS It is anticipated that the implementation of this dataset in routine clinical practise will inform patient treatment as well as provide standardized information relating to outcome prediction. The harmonisation of data reporting should also facilitate international research collaborations. This article is protected by copyright. All rights reserved.

© 2019 Background: The prevalence of multi-morbidity in implantable cardioverter defibrillator (ICD) recipients is approximately 25%. Multi-morbidity is associated with poor health and psychological outcomes in this population and may affect ICD recipients’ quality-of-life (QOL). The purpose of this study was to determine the prevalence of psychological distress (anxiety, depressive symptoms, and Type-D personality) in ICD recipients with varying levels of comorbidities, and to examine the association between multi-morbidity burden and QOL in this population. Methods: All adults listed in the Swedish ICD and Pacemaker Registry in 2012 with an ICD implanted for at least one year were invited to participate in this study. Binary logistic regression was used to predict QOL using the EQ-5D mean index dichotomized based on median QOL scores. Multi-morbidity burden scores were based on quartile groupings. Results: A total of 2658 ICD recipients participated in the study (with a mean age of 65, 20.6% female, mean implant duration of 4.7 years, with 35.4% implanted for primary prevention of sudden cardiac arrest). Greater multi-morbidity burden, female sex, not working outside the home, history of ICD shock, negative ICD experience, higher levels of ICD-related concerns, and the presence of anxiety, depression, or Type D personality were associated with worse QOL in ICD recipients. Predictors differed by multi-morbidity burden level. Conclusions: Multi-morbidity burden and psychological distress is an essential factor related to QOL. This issue should be discussed with potential ICD recipients prior to implant. Further exploration of increased recognition and treatment of psychological distress in ICD recipients is warranted.

© 2019 Background: The prevalence of multi-morbidity in implantable cardioverter defibrillator (ICD) recipients is approximately 25%. Multi-morbidity is associated with poor health and psychological outcomes in this population and may affect ICD recipients’ quality-of-life (QOL). The purpose of this study was to determine the prevalence of psychological distress (anxiety, depressive symptoms, and Type-D personality) in ICD recipients with varying levels of comorbidities, and to examine the association between multi-morbidity burden and QOL in this population. Methods: All adults listed in the Swedish ICD and Pacemaker Registry in 2012 with an ICD implanted for at least one year were invited to participate in this study. Binary logistic regression was used to predict QOL using the EQ-5D mean index dichotomized based on median QOL scores. Multi-morbidity burden scores were based on quartile groupings. Results: A total of 2658 ICD recipients participated in the study (with a mean age of 65, 20.6% female, mean implant duration of 4.7 years, with 35.4% implanted for primary prevention of sudden cardiac arrest). Greater multi-morbidity burden, female sex, not working outside the home, history of ICD shock, negative ICD experience, higher levels of ICD-related concerns, and the presence of anxiety, depression, or Type D personality were associated with worse QOL in ICD recipients. Predictors differed by multi-morbidity burden level. Conclusions: Multi-morbidity burden and psychological distress is an essential factor related to QOL. This issue should be discussed with potential ICD recipients prior to implant. Further exploration of increased recognition and treatment of psychological distress in ICD recipients is warranted.

The fibre drawing technique is utilized for fabricating metamaterials. The ability to engineer both the permittivity and permeability is demonstrated. A hyperlens with λ/176 sub-diffraction focusing is realized. Tunability of 50% is also demonstrated.

Background: MRD monitoring in ALL is a strong predictive factor and a stratification tool for treatment intensification. The currently accepted standard of molecular monitoring with either immunoglobin heavy or kappa chain (IG) or T-cell receptor (TCR) quantitative PCR (qPCR) in Philadelphia negative (Ph-) ALL offers high sensitivity, but accessibility is limited by expertise, cost and turnaround time. Flow cytometric assays are increasingly utilised and improved sensitivity is seen with multi-parameter flow cytometry at 8 or more colours. Method(s): We developed a 10-colour single tube flow cytometry assay (Figure 1). Samples were subject to bulk ammonium chloride lysis to maximise cell yields with a target of 1 x 106 events. Once normal maturation patterns were established, patient samples were analysed in parallel to standard molecular monitoring with either IG/TCR qPCR in Ph-disease or BCR-ABL qRT-PCR in Ph+ disease. Statistical analysis was performed in Graphpad Prism v7.0. Result(s): Flow cytometry was performed on 47 samples from 16 patients. 13 samples were at diagnosis or morphologic relapse. An informative immunophenotype was identifiable in all patients; however a molecular assay could not able to be developed in one patient. 38 samples were tested for MRD by flow cytometry (Figure 2). In 2 samples, flow cyto-metric MRD was detected despite blinatumomab (anti-CD19) therapy. 27 samples were tested concurrently for MRD by both molecular and flow cytometric methods (Figure 3A and 3B). There was a strong correlation between molecular and flow cytometric MRD (R2=0.909, p<0.001; Figure 3B). Correlation was strong with both IG/TCR-based (n=16; R2=0.955, p<0.001) and BCR-ABL-based (n= 11; R2=0.957, p<0.001) (Figure Presented) assays. The cost was significantly lower than IG/TCR qPCR (eg. Cost for four time-points per patient approximately $1200 vs $3700). Conclusion(s): Our 10-colour flow cytometric MRD assay attained sensitivity of <=0.01% in 87% of samples, and

Background: MRD monitoring in ALL is a strong predictive factor and a stratification tool for treatment intensification. The currently accepted standard of molecular monitoring with either immunoglobin heavy or kappa chain (IG) or T-cell receptor (TCR) quantitative PCR (qPCR) in Philadelphia negative (Ph-) ALL offers high sensitivity, but accessibility is limited by expertise, cost and turnaround time. Flow cytometric assays are increasingly utilised and improved sensitivity is seen with multi-parameter flow cytometry at 8 or more colours. Method(s): We developed a 10-colour single tube flow cytometry assay (Figure 1). Samples were subject to bulk ammonium chloride lysis to maximise cell yields with a target of 1 x 106 events. Once normal maturation patterns were established, patient samples were analysed in parallel to standard molecular monitoring with either IG/TCR qPCR in Ph-disease or BCR-ABL qRT-PCR in Ph+ disease. Statistical analysis was performed in Graphpad Prism v7.0. Result(s): Flow cytometry was performed on 47 samples from 16 patients. 13 samples were at diagnosis or morphologic relapse. An informative immunophenotype was identifiable in all patients; however a molecular assay could not able to be developed in one patient. 38 samples were tested for MRD by flow cytometry (Figure 2). In 2 samples, flow cyto-metric MRD was detected despite blinatumomab (anti-CD19) therapy. 27 samples were tested concurrently for MRD by both molecular and flow cytometric methods (Figure 3A and 3B). There was a strong correlation between molecular and flow cytometric MRD (R2=0.909, p<0.001; Figure 3B). Correlation was strong with both IG/TCR-based (n=16; R2=0.955, p<0.001) and BCR-ABL-based (n= 11; R2=0.957, p<0.001) (Figure Presented) assays. The cost was significantly lower than IG/TCR qPCR (eg. Cost for four time-points per patient approximately $1200 vs $3700). Conclusion(s): Our 10-colour flow cytometric MRD assay attained sensitivity of <=0.01% in 87% of samples, and

OBJECTIVES: Core-binding factor acute myeloid leukaemia (CBF AML) defined by t(8;21)(q22;q22) or inv(16)(p13q22)/t(16;16)(p13;q22) has a favourable prognosis; however, 30%-40% of patients still relapse after chemotherapy. We sought to evaluate the risk factors for relapse in a de novo CBF AML cohort. PATIENTS/MATERIALS/METHODS: A retrospective review of patients from four Australian tertiary centres from 2001 to 2012, comprising 40 t(8;21) and 30 inv(16) AMLs. RESULTS: Multivariate analysis identified age (P = .032) and white cell count (WCC)>40 (P = .025) as significant predictors for inferior OS and relapse, respectively. Relapse risk was higher in the inv(16) group vs the t(8;21) group (57% vs 18%, HR 4.31, 95% CI: 1.78-10.42, P = .001). Induction therapy had no bearing on OS or relapse-free survival (RFS); however, consolidation treatment with >3 cycles of intermediate-/high-dose cytarabine improved OS (P = .035) and RFS (P = .063). Five patients demonstrated post-treatment stable q PCR positivity without relapse. CONCLUSIONS: >3 consolidation cycles of intermediate-/high-dose cytarabine improves patient outcomes Age and inv(16) CBF AML subtype are predictors of inferior OS and RFS, respectively. Stable low-level MRD by qPCR does not predict relapse Similar OS in the inv(16) cohort compared to the t(8;21) cohort, despite a higher relapse rate, confirms salvageability of relapsed disease.

Background: Minimal residual disease (MRD) monitoring in Acute Lymphoblastic Leukemia (ALL) is an accepted standard of care in both adult and pediatric patients as one of the strongest predictive factors for disease outcome and as a stratification tool for treatment intensification and allogeneic stem cell transplant. The currently accepted standard of molecular monitoring with either immunoglobin heavy or kappa chain (IG) or T-cell receptor (TCR) quantitative PCR (qPCR) in Philadelphia negative ALL allows for sensitive monitoring of MRD, but requires a high degree of expertise, and factors such as cost and turnaround time may limit generalized applicability of this technique. Flow cytometric MRD monitoring is utilized in many centers, with increased sensitivity seen with implementation of multi-parameter flow cytometry at 8-colours or more. Aim(s): We sought to compare a 10-color flow cytometry assay for detecting MRD in B-ALL with standard molecular monitoring. Method(s): To facilitate rapid identification of MRD in patients with B-ALL, we developed a 10-colour single tube flow cytometry assay utilizing CD19, CD22, CD20, CD38, CD58, CD13/33, CD66c, CD10, CD45 and CD34 as markers. These markers were selected to provide at least two targets for identification of B-lineage cells, and to include the most frequently aberrant markers in precursor B-lineage ALL. Samples were subject to bulk ammonium chloride lysis to maximize cell yields with a target of 1 x 106 events. Once normal maturation patterns were established, patient samples were analyzed in parallel to standard of care molecular monitoring with either IG/TCR qPCR in Philadelphia negative (Ph-) disease and BCR-ABL qRT-PCR in Philadelphia positive (Ph+) disease. Statistical correlation was performed in Graphpad Prism version 7.0 for linear regression and calculation of correlation co-efficient. (Table Presented) Results: 33 samples at different time points from 13 patients were analyzed by flow cytometry. 9 samp

Background: Dasatinib (DAS) has shown superiority over imatinib in achieving cytogenetic and molecular responses in chronic phase (CP) CML but with a different toxicity profile, which may impact on its overall benefit. Reported tox- icities from the DASISION trial at 5 years include pleural effusions (PE) (29%), pulmonary hypertension (PHTN) (5%), and low rates of arterial ischemic events. While the literature well describes the incidence of these events, the response to therapy and the impact of subsequent dose modifications on the outcome of the toxicity have generally not been comprehensively characterised. Aim(s): To review the incidence of these side-effects in a snapshot survey of Australian patients (pts) receiving DAS, either as first or subsequent line of therapy for CML-CP, with a focus on risk factors and the response of the toxicity to therapeutic changes. Method(s): Retrospective study of all eligible pts (received DAS for CML-CP and access to sufficient data) at 17 Australian institutions. Each pt's history was tracked in detail to identify any complications potentially attributable to DAS, and the treatment and outcome of these complications in response to cessation or alterations in DAS dose or schedule. Result(s): 221 pts were evaluable, with a median age at DAS commencement of 53 years (range 20 - 86) and median starting dose of 100mg (20-140). 51 (23%) received DAS as 1st line therapy, 133 (60%) 2nd line and 37 (17%) 3rd line. The median follow up from DAS commencement was 27 months (4 -116 months). No side effects were reported in 105 (48%) pts. Of the 116 (52%) pts with side-effects, the most common side effect was PE, observed in 53 (24%) pts with a median age of 65 years (41-86 years) and with median time to onset of 11 months (0.5-59 months). Most (40 pts, 76%) were receiving DAS as 2nd line therapy. DAS dose at PE onset was 100mg in 37 pts (70%), 140mg in 9 pts (17% PEs; notably 38% of pts on this dose developed PE), 70mg in 4 pts, 80mg in 2

APOGEE-2 is a high-resolution, near-infrared spectroscopic survey observing roughly 300,000 stars across the entire sky. It is the successor to APOGEE and is part of the Sloan Digital Sky Survey IV (SDSS-IV). APOGEE-2 is expanding upon APOGEE's goals of addressing critical questions of stellar astrophysics, stellar populations, and Galactic chemodynamical evolution using (1) an enhanced set of target types and (2) a second spectrograph at Las Campanas Observatory in Chile. APOGEE-2 is targeting red giant branch (RGB) and red clump (RC) stars, RR Lyrae, low-mass dwarf stars, young stellar objects, and numerous other Milky Way and Local Group sources across the entire sky from both hemispheres. In this paper, we describe the APOGEE-2 observational design, target selection catalogs and algorithms, and the targeting-related documentation included in the SDSS data releases., Comment: 19 pages, 6 figures. Accepted to AJ

Background: Minimal residual disease (MRD) monitoring in Acute Lymphoblastic Leukemia (ALL) is an accepted standard of care in both adult and pediatric patients as one of the strongest predictive factors for disease outcome and as a stratification tool for treatment intensification and allogeneic stem cell transplant. The currently accepted standard of molecular monitoring with either immunoglobin heavy or kappa chain (IG) or T-cell receptor (TCR) quantitative PCR (qPCR) in Philadelphia negative ALL allows for sensitive monitoring of MRD, but requires a high degree of expertise, and factors such as cost and turnaround time may limit generalized applicability of this technique. Flow cytometric MRD monitoring is utilized in many centers, with increased sensitivity seen with implementation of multi-parameter flow cytometry at 8-colours or more. Aim(s): We sought to compare a 10-color flow cytometry assay for detecting MRD in B-ALL with standard molecular monitoring. Method(s): To facilitate rapid identification of MRD in patients with B-ALL, we developed a 10-colour single tube flow cytometry assay utilizing CD19, CD22, CD20, CD38, CD58, CD13/33, CD66c, CD10, CD45 and CD34 as markers. These markers were selected to provide at least two targets for identification of B-lineage cells, and to include the most frequently aberrant markers in precursor B-lineage ALL. Samples were subject to bulk ammonium chloride lysis to maximize cell yields with a target of 1 x 106 events. Once normal maturation patterns were established, patient samples were analyzed in parallel to standard of care molecular monitoring with either IG/TCR qPCR in Philadelphia negative (Ph-) disease and BCR-ABL qRT-PCR in Philadelphia positive (Ph+) disease. Statistical correlation was performed in Graphpad Prism version 7.0 for linear regression and calculation of correlation co-efficient. (Table Presented) Results: 33 samples at different time points from 13 patients were analyzed by flow cytometry. 9 samp

Background: Dasatinib (DAS) has shown superiority over imatinib in achieving cytogenetic and molecular responses in chronic phase (CP) CML but with a different toxicity profile, which may impact on its overall benefit. Reported tox- icities from the DASISION trial at 5 years include pleural effusions (PE) (29%), pulmonary hypertension (PHTN) (5%), and low rates of arterial ischemic events. While the literature well describes the incidence of these events, the response to therapy and the impact of subsequent dose modifications on the outcome of the toxicity have generally not been comprehensively characterised. Aim(s): To review the incidence of these side-effects in a snapshot survey of Australian patients (pts) receiving DAS, either as first or subsequent line of therapy for CML-CP, with a focus on risk factors and the response of the toxicity to therapeutic changes. Method(s): Retrospective study of all eligible pts (received DAS for CML-CP and access to sufficient data) at 17 Australian institutions. Each pt's history was tracked in detail to identify any complications potentially attributable to DAS, and the treatment and outcome of these complications in response to cessation or alterations in DAS dose or schedule. Result(s): 221 pts were evaluable, with a median age at DAS commencement of 53 years (range 20 - 86) and median starting dose of 100mg (20-140). 51 (23%) received DAS as 1st line therapy, 133 (60%) 2nd line and 37 (17%) 3rd line. The median follow up from DAS commencement was 27 months (4 -116 months). No side effects were reported in 105 (48%) pts. Of the 116 (52%) pts with side-effects, the most common side effect was PE, observed in 53 (24%) pts with a median age of 65 years (41-86 years) and with median time to onset of 11 months (0.5-59 months). Most (40 pts, 76%) were receiving DAS as 2nd line therapy. DAS dose at PE onset was 100mg in 37 pts (70%), 140mg in 9 pts (17% PEs; notably 38% of pts on this dose developed PE), 70mg in 4 pts, 80mg in 2

APOGEE-2 is a high-resolution, near-infrared spectroscopic survey observing roughly 300,000 stars across the entire sky. It is the successor to APOGEE and is part of the Sloan Digital Sky Survey IV (SDSS-IV). APOGEE-2 is expanding upon APOGEE's goals of addressing critical questions of stellar astrophysics, stellar populations, and Galactic chemodynamical evolution using (1) an enhanced set of target types and (2) a second spectrograph at Las Campanas Observatory in Chile. APOGEE-2 is targeting red giant branch (RGB) and red clump (RC) stars, RR Lyrae, low-mass dwarf stars, young stellar objects, and numerous other Milky Way and Local Group sources across the entire sky from both hemispheres. In this paper, we describe the APOGEE-2 observational design, target selection catalogs and algorithms, and the targeting-related documentation included in the SDSS data releases., Comment: 19 pages, 6 figures. Accepted to AJ

Objective: Athlete development and management encompass a complex interaction of biological, psychological, and social factors. Within elite sport, multidisciplinary sport science and medicine teams play an important role in achieving an optimal balance between preventing athlete ill-health and optimizing health and performance. The psychological aspects of athlete health and performance have gained increased attention over the past two decades, with much of this research concerned with the mental health of athletes and the concept of mental toughness. Recently, it was proposed that mental health and mental toughness are contradictory concepts in the world of elite sport. Although an interesting proposition, this claim was not substantiated. Thus, the purpose of this narrative review was to evaluate theory and evidence regarding the thesis that mental health and mental toughness are contradictory concepts in the world of elite sport, with the view to advance scholarly knowledge and inform professional practice. Design: Narrative review. Results: A critical evaluation of this literature suggests that mental toughness may represent a positive indicator of mental health, or facilitate its attainment, rather than be at odds with it. Conclusion: When implemented alongside multilayered approaches to organizational change (e.g., group structures, policies), mental toughness could be used as a 'hook' to attract athletes into settings that can open dialogue on the importance of mental health and improve knowledge of key issues (e.g., stigma, symptoms).

We report the first metamaterial tapered hyperlens for operation in the mid-infrared (3 μm) made of 470 tin wires embedded in soda-lime glass. The taper presents a magnification of 2x and is 62.5 μm in length. The structure on the smallest side has an average wire diameter and spacing of 300 and 600 nm, respectively. Preliminary modeling of the hyperlens indicates that the overall loss for the high spatial frequency modes in such a device is smaller than 36 dB, making sub-diffraction imaging feasible.

We present an elemental-abundance analysis of an extremely metal-poor (EMP; [Fe/H] < -3.0) star, SDSS J134338.67+484426.6, identified during the course of the MARVELS spectroscopic pre-survey of some 20000 stars to identify suitable candidates for exoplanet searches. This star, with an apparent magnitude V = 12.14, is the lowest metallicity star found in the pre-survey, and is one of only ~20 known EMP stars that are this bright or brighter. Our high-resolution spectroscopic analysis shows that this star is a subgiant with [Fe/H] = -3.42, having "normal" carbon and no enhancement of neutron-capture abundances. Strontium is under-abundant, [Sr/Fe] =-0.47, but the derived lower limit on [Sr/Ba] indicates that Sr is likely enhanced relative to Ba. This star belongs to the sparsely populated class of alpha-poor EMP stars that exhibit low ratios of [Mg/Fe], [Si/Fe], and [Ca/Fe] compared to typical halo stars at similar metallicity. The observed variations in radial velocity from several epochs of (low- and high-resolution) spectroscopic follow-up indicate that SDSS J134338.67+484426.6 is a possible long-period binary. We also discuss the abundance trends in EMP stars for r-process elements, and compare with other magnesium-poor stars., Comment: 11 pages, 10 figures, Accepted for publication in MNRAS

Muscle invasive urinary bladder cancer is one of the most lethal cancers and its detection at the time of transurethral resection remains limited and diagnostic methods are urgently needed. We have developed a muscle invasive transitional cell carcinoma (TCC) model of the bladder using porcine bladder scaffold and the human bladder cancer cell line 5637. The progression of implanted cancer cells to muscle invasion can be monitored by measuring changes in the spectrum of endogenous fluorophores such as reduced nicotinamide dinucleotide (NADH) and flavins. We believe this could act as a useful tool for the study of fluorescence dynamics of developing muscle invasive bladder cancer in patients. Published by The Optical Society under the terms of the Creative Commons Attribution 4.0 License. Further distribution of this work must maintain attribution to the author(s) and the published article's title, journal citation, and DOI.

Muscle invasive urinary bladder cancer is one of the most lethal cancers and its detection at the time of transurethral resection remains limited and diagnostic methods are urgently needed. We have developed a muscle invasive transitional cell carcinoma (TCC) model of the bladder using porcine bladder scaffold and the human bladder cancer cell line 5637. The progression of implanted cancer cells to muscle invasion can be monitored by measuring changes in the spectrum of endogenous fluorophores such as reduced nicotinamide dinucleotide (NADH) and flavins. We believe this could act as a useful tool for the study of fluorescence dynamics of developing muscle invasive bladder cancer in patients. Published by The Optical Society under the terms of the Creative Commons Attribution 4.0 License. Further distribution of this work must maintain attribution to the author(s) and the published article's title, journal citation, and DOI.

We present an elemental-abundance analysis of an extremely metal-poor (EMP; [Fe/H] < -3.0) star, SDSS J134338.67+484426.6, identified during the course of the MARVELS spectroscopic pre-survey of some 20000 stars to identify suitable candidates for exoplanet searches. This star, with an apparent magnitude V = 12.14, is the lowest metallicity star found in the pre-survey, and is one of only ~20 known EMP stars that are this bright or brighter. Our high-resolution spectroscopic analysis shows that this star is a subgiant with [Fe/H] = -3.42, having "normal" carbon and no enhancement of neutron-capture abundances. Strontium is under-abundant, [Sr/Fe] =-0.47, but the derived lower limit on [Sr/Ba] indicates that Sr is likely enhanced relative to Ba. This star belongs to the sparsely populated class of alpha-poor EMP stars that exhibit low ratios of [Mg/Fe], [Si/Fe], and [Ca/Fe] compared to typical halo stars at similar metallicity. The observed variations in radial velocity from several epochs of (low- and high-resolution) spectroscopic follow-up indicate that SDSS J134338.67+484426.6 is a possible long-period binary. We also discuss the abundance trends in EMP stars for r-process elements, and compare with other magnesium-poor stars., Comment: 11 pages, 10 figures, Accepted for publication in MNRAS

There is a strong argument for the use of antifungal prophylaxis in high-risk patients given the significant mortality associated with invasive fungal disease, the late identification of these infections, and the availability of safe and well-tolerated prophylactic medications. Clinical decisions about which patients should receive prophylaxis and choice of antifungal agent should be guided by risk stratification, knowledge of local fungal epidemiology, the efficacy and tolerability profile of available agents, and estimates such as number needed to treat and number needed to harm. There have been substantial changes in practice since the 2008 guidelines were published. These include the availability of new medications and/or formulations, and a focus on refining and simplifying patient risk stratification. Used in context, these guidelines aim to assist clinicians in providing optimal preventive care to this vulnerable patient demographic.Copyright © 2014 The Authors; Internal Medicine Journal © 2014 Royal Australasian College of Physicians.

There is a strong argument for the use of antifungal prophylaxis in high-risk patients given the significant mortality associated with invasive fungal disease, the late identification of these infections, and the availability of safe and well-tolerated prophylactic medications. Clinical decisions about which patients should receive prophylaxis and choice of antifungal agent should be guided by risk stratification, knowledge of local fungal epidemiology, the efficacy and tolerability profile of available agents, and estimates such as number needed to treat and number needed to harm. There have been substantial changes in practice since the 2008 guidelines were published. These include the availability of new medications and/or formulations, and a focus on refining and simplifying patient risk stratification. Used in context, these guidelines aim to assist clinicians in providing optimal preventive care to this vulnerable patient demographic.Copyright © 2014 The Authors; Internal Medicine Journal © 2014 Royal Australasian College of Physicians.

Network connectivity offers the potential for a group of musicians to play together over the network. This paper describes a trans-Atlantic networked musical livecoding performance between Andrew Sorensen in Germany (at the Schloss Daghstuhl conference on Collaboration and Learning through Live Coding) and Ben Swift in San Jose (at YL/HCC) in September 2013. In this paper we describe the infrastructure developed to enable this performance.

We are carrying out a large ancillary program with the SDSS-III, using the fiber-fed multi-object NIR APOGEE spectrograph, to obtain high-resolution H-band spectra of more than 1200 M dwarfs. These observations are used to measure spectroscopic rotational velocities, radial velocities, physical stellar parameters, and variability of the target stars. Here, we describe the target selection for this survey and results from the first year of scientific observations based on spectra that is publicly available in the SDSS-III DR10 data release. As part of this paper we present RVs and vsini of over 200 M dwarfs, with a vsini precision of ~2 km/s and a measurement floor at vsini = 4 km/s. This survey significantly increases the number of M dwarfs studied for vsini and RV variability (at ~100-200 m/s), and will advance the target selection for planned RV and photometric searches for low mass exoplanets around M dwarfs, such as HPF, CARMENES, and TESS. Multiple epochs of radial velocity observations enable us to identify short period binaries, and AO imaging of a subset of stars enables the detection of possible stellar companions at larger separations. The high-resolution H-band APOGEE spectra provide the opportunity to measure physical stellar parameters such as effective temperatures and metallicities for many of these stars. At the culmination of this survey, we will have obtained multi-epoch spectra and RVs for over 1400 stars spanning spectral types of M0-L0, providing the largest set of NIR M dwarf spectra at high resolution, and more than doubling the number of known spectroscopic vsini values for M dwarfs. Furthermore, by modeling telluric lines to correct for small instrumental radial velocity shifts, we hope to achieve a relative velocity precision floor of 50 m/s for bright M dwarfs. We present preliminary results of this telluric modeling technique in this paper., Comment: Submitted to Astronomical Journal

The Apache Point Observatory Galactic Evolution Experiment (APOGEE) is a high-resolution infrared spectroscopic survey spanning all Galactic environments (i.e., bulge, disk, and halo), with the principal goal of constraining dynamical and chemical evolution models of the Milky Way. APOGEE takes advantage of the reduced effects of extinction at infrared wavelengths to observe the inner Galaxy and bulge at an unprecedented level of detail. The survey's broad spatial and wavelength coverage enables users of APOGEE data to address numerous Galactic structure and stellar populations issues. In this paper we describe the APOGEE targeting scheme and document its various target classes to provide the necessary background and reference information to analyze samples of APOGEE data with awareness of the imposed selection criteria and resulting sample properties. APOGEE's primary sample consists of ~100,000 red giant stars, selected to minimize observational biases in age and metallicity. We present the methodology and considerations that drive the selection of this sample and evaluate the accuracy, efficiency, and caveats of the selection and sampling algorithms. We also describe additional target classes that contribute to the APOGEE sample, including numerous ancillary science programs, and we outline the targeting data that will be included in the public data releases., Comment: Accepted to AJ. 31 pages, 11 figures