A pharmacokinetic model for hyperpolarized 13C-pyruvate MRI when using metabolite-specific bSSFP sequences.

PURPOSE: Metabolite-specific balanced SSFP (MS-bSSFP) sequences are increasingly used in hyperpolarized [1-13C]Pyruvate (HP 13C) MRI studies as they improve SNR by refocusing the magnetization each TR. Currently, pharmacokinetic models used to fit conversion rate constants, kPL and kPB, and rate constant maps do not account for differences in the signal evolution of MS-bSSFP acquisitions. METHODS: In this work, a flexible MS-bSSFP model was built that can be used to fit conversion rate constants for these experiments. The model was validated in vivo using paired animal (healthy rat kidneys n = 8, transgenic adenocarcinoma of the mouse prostate n = 3) and human renal cell carcinoma (n = 3) datasets. Gradient echo (GRE) acquisitions were used with a previous GRE model to compare to the results of the proposed GRE-bSSFP model. RESULTS: Within simulations, the proposed GRE-bSSFP model fits the simulated data well, whereas a GRE model shows bias because of model mismatch. For the in vivo datasets, the estimated conversion rate constants using the proposed GRE-bSSFP model are consistent with a previous GRE model. Jointly fitting the lactate T2 with kPL resulted in less precise kPL estimates. CONCLUSION: The proposed GRE-bSSFP model provides a method to estimate conversion rate constants, kPL and kPB, for MS-bSSFP HP 13C experiments. This model may also be modified and used for other applications, for example, estimating rate constants with other hyperpolarized reagents or multi-echo bSSFP.

Nickel hypersensitivity and skin patch testing in total hip replacement surgery: a systematic review.

Approximately 60,000 cemented femoral stems are implanted in the UK each year with the majority being manufactured from stainless steel containing 10-15% nickel. Nickel hypersensitivity has been reported in up to 13% of the general population and there is a concern that nickel hypersensitivity might adversely affect the outcome of total hip replacement (THR). We reviewed the current literature on the potential link between nickel hypersensitivity and THR complications, and the usefulness of patch testing.We conducted a literature search in PubMed, MEDLINE and EMBASE databases. The level of evidence and the quality of the selected studies were assessed using the Oxford Centre for Evidence-Based Medicine Criteria and the Methodological Index for Non-Randomised Studies tool, respectively.Twenty-six studies met the inclusion criteria, reporting on 1852 patients who underwent primary or revision THR. All studies detailed skin patch testing and recorded prevalence of nickel hypersensitivity from 1.5% to 33.3%. Five studies reported a rise in Nickel hypersensitivity following THR, while four reported a decreased prevalence post-operatively. Eight studies concluded that metal hypersensitivity could have developed following THR, while seven studies did not support a link between metal hypersensitivity and THR complications. Four of the studies recommended routine patch testing pre-operatively, but three others concluded that routine patch testing was not indicated.We have not identified a link between nickel hypersensitivity and THR complications, and the role of patch testing remains unclear. Further large-scale studies would be required to investigate this relationship and to clarify the role of patch testing in facilitating implant selection. Cite this article: EFORT Open Rev 2021;6:825-838. DOI: 10.1302/2058-5241.6.210051.

The prevalence and clinical associations of ultrasound measures of congestion in patients at risk of developing heart failure.

AIMS: Congestion is a cardinal feature of untreated heart failure (HF) and might be detected by ultrasound (US) before overt clinical signs appear. METHODS AND RESULTS: We investigated the prevalence and clinical associations of subclinical congestion in 238 patients with at least one clinical risk factor for HF (diabetes, ischaemic heart disease, or hypertension) using three US variables: (i) inferior vena cava (IVC) diameter; (ii) jugular vein distensibility (JVD) ratio (the ratio of the jugular vein diameter during the Valsalva manoeuvre to that at rest); (iii) the number of B-lines from a 28-point lung US. US congestion was defined as IVC diameter > 2.0 cm, JVD ratio < 4.0 or B-lines count > 14. The prevalence of subclinical congestion (defined as at least one positive US marker of congestion) was 30% (13% by IVC diameter, 9% by JVD ratio and 13% by B-line quantification). Compared to patients with no congestion on US, those with at least one marker had larger left atria and higher plasma concentrations of natriuretic peptides. Patients with raised plasma N-terminal pro-B-type natriuretic peptide/B-type natriuretic peptide had a lower JVD ratio (7.69 vs. 8.80; P = 0.05) and more often had at least one lung B-line (74% vs. 63%; P = 0.05). However, plasma natriuretic peptide concentrations were more closely related to left atrial volume than other US measures of congestion. CONCLUSIONS: Subclinical evidence of congestion by US is common in patients with clinical risk factors for HF. Whether these measurements provide additional value for predicting the development of HF and its prevention deserves consideration.

A comparison of non-invasive methods of measuring body composition in patients with heart failure: a report from SICA-HF.

BACKGROUND: Cachexia is common in patients with chronic heart failure and is associated with poor prognosis. How best to measure body composition is not clear. METHODS AND RESULTS: We characterized body composition in 120 patients with chronic heart failure: mean (SD) age 70 (10) years, left ventricular ejection fraction 44 (10) %, and median (Q1-Q3) N-terminal pro B-type natriuretic peptide 845 (355-1368) ng/L. We measured body composition using dual-energy X-ray absorptiometry (DEXA) and a multi-frequency bioelectrical impedance analysis (BIA) device (Tanita BIA MC-180MA). Mean (SD) fat mass (FM) was 27.2 (11.7) kg by BIA and 32.3 (12.2) kg by DEXA (mean difference -5.1 kg, 95% limits of agreement: -11.7, 1.5; 4% of values outside limit of agreement); mean (SD) lean mass (LM) was 56.6 (10.9) kg by BIA and 51.1 (9.9) kg by DEXA (mean difference 5.5 kg, 95% limits of agreement: -1.3, 12.3; 6% of values outside limit of agreement); and mean (SD) bone mass (BM) was 3.0 (0.5) kg by BIA and 2.8 (0.6) kg by DEXA (mean difference 0.2 kg, 95% limits of agreement: -0.5, 0.8; 5% of values outside limit of agreement). There was a close correlation between DEXA and BIA for both LM and FM (LM: r = 0.95, P < 0.001; FM: r = 0.96, P < 0.001) but less so for BM (r = 0.84, P < 0.001). Both DEXA and BIA body composition measurements correlated well with other measures of body size (body mass index, hip circumference, and waist circumference). CONCLUSIONS: There are differences in the measurements of FM, LM, and BM between the two techniques, which should not be used interchangeably.

"The Road We Travel": Developing a co-produced narrative for a photovoice project.

WHAT IS KNOWN ON THE SUBJECT?: PhotoVoice as a participatory methodology has been used within mental health to support marginalized communities in addressing the challenges they encounter. The PhotoVoice methodology aims to encourage and foster collaborative and equal partnerships. However, reports of previous projects highlight that not every stage of the process remains participant-centric. There is limited reporting on participant involvement in the latter stages of projects, such as exhibition design. WHAT THE PAPER ADDS TO EXISTING KNOWLEDGE?: It provides a detailed description of the phases involved in planning and executing a mental health PhotoVoice project. It provides an illustration of how collaborative partnerships can extend into the design and construction of a photography exhibition and its narrative. WHAT ARE THE IMPLICATIONS FOR PRACTICE?: PhotoVoice is an ideal methodology for use within the field of mental health nursing as it promotes service user inclusion in research, places value on lived experiences and provides a creative medium through which service users and family members can advocate for themselves and others. PhotoVoice is an effective and creative methodology for disseminating and communicating both the individual and collective outcomes to the general public. When implementing this methodology, clinicians and researchers need to be cognisant of the necessity to include participants as equal partners at every stage, including in the design of photography exhibitions and disseminating the findings to academic and public audiences. ABSTRACT: Introduction PhotoVoice is a participatory methodology in which marginalized communities represent their lived experiences through photography. While the methodology aims to foster partnerships throughout all phases, the literature suggests that in the field of mental health, some phases are often completed without participant involvement. Aims This paper elaborates on how the PhotoVoice method was used to engage service users and family members around their experience of involvement in a co-produced and co-facilitated mental health education intervention, in order to enhance public and policymakers knowledge of the project. Methods Ten participants were recruited and trained in the PhotoVoice method. Participants documented, through photography, their experiences of involvement in the education intervention. Following this, participants came together to co-produce and disseminate the photography exhibition to the public. Results PhotoVoice proved to be a flexible and creative method by which to include marginalized groups. By adhering to the collaborative principles of the methodology, service users and family members can retain decision-making power from the project's inception to its conclusion. Implications for Practice PhotoVoice is ideal for use within mental health nursing as it coincides with the recovery principle of promoting collaborative partnership between service users, family members and clinicians. Mental health nurses work directly with service users and family members throughout their recovery journey. The PhotoVoice methodology is coherent with the recovery principles of empowerment, collaboration and prioritizing the lived experiences of the individual. As such, this methodology has the potential to enhance greatly what mental health nurses can know and understand about the lived experiences of service users and family members. In turn, engaging with the PhotoVoice methodology can provide a platform from which further collaborative engagement between service users, family members and clinicians can take place.

Lights and darks of neuroendocrine tumors of the appendix.

INTRODUCTION: Neuroendocrine tumors of the appendix are a relatively frequent type of neuroendocrine tumor, usually detected incidentally after appendectomy. Almost all small slow-growing G1 tumors with no risk factors are cured with appendectomy while the rare and aggressive G3 carcinomas may represent a challenge in terms of management and often lead to a poor outcome. In the middle of the spectrum, a number of tumors present with in-between features and sometimes no clear-cut guidance emerges from the literature for directing the management and follow-up of these patients. EVIDENCE ACQUISITION: A meticulous review of the literature on neuroendocrine tumors of the appendix, including the recommendations published by the relevant international societies. EVIDENCE SYNTHESIS: The literature on the neuroendocrine tumors of the appendix appears to be inhomogeneous. Likely this occurs as a consequence of a number of factors, including the mostly retrospective nature of the available data, the heterogeneous records of the same, and some peculiar aspects of the appendiceal neuroendocrine tumors, with evidence of considerable biological and clinical differences in terms of epidemiology, management, and prognosis from the less aggressive tumors to the most aggressive cancers. In particular, some situations concerning tumors in the middle of the biological and clinical spectrum are still poorly defined. CONCLUSIONS: There are some persisting "grey areas" with regard to the characterization and the clinical management of neuroendocrine tumors of the appendix. An increasing awareness of the biological and clinical aspects of this disease and new, ideally prospective, focused studies might help and clarify some relevant issues that are not fully elucidated yet and could increase the solidity of the guidance for the management and the follow-up of the patients.

A Preliminary Cohort Study Assessing Routine Blood Analyte Levels and Neurological Outcome after Spinal Cord Injury.

There is increasing interest in the identification of biomarkers that could predict neurological outcome following a spinal cord injury (SCI). Although initial American Spinal Injury Association (ASIA) Impairment Scale (AIS) grade is a good indicator of neurological outcome, for the patient and clinicians, an element of uncertainty remains. This preliminary study aimed to assess the additive potential of routine blood analytes following principal component analysis (PCA) to develop prognostic models for neurological outcome following SCI. Routine blood and clinical data were collected from SCI patients (n = 82) and PCA used to reduce the number of blood analytes into related factors. Outcome neurology was obtained from AIS scores at 3 and 12 months post-injury, with motor (AIS and total including all myotomes) and sensory (AIS, touch and pain) abilities being assessed individually. Multiple regression models were created for all outcome measures. Blood analytes relating to "liver function" and "acute inflammation and liver function" factors were found to significantly increase prediction of neurological outcome at both 3 months (touch, pain, and AIS sensory) and at 1 year (pain, R2 increased by 0.025 and total motor, R2 increased by 0.016). For some models "liver function" and "acute inflammation and liver function" factors were both significantly predictive, with the greatest combined R2 improvement of 0.043 occurring for 3 month pain prediction. These preliminary findings support ongoing research into the use of routine blood analytes in the prediction of neurological outcome in SCI patients.

Clinical and prognostic association of total atrial conduction time in patients with heart failure: a report from Studies Investigating Co-morbidities Aggravating Heart Failure.

BACKGROUND: The total atrial conduction time can be measured as the time from the onset of the P wave on the ECG to the peak of the A wave recorded at the mitral annulus using tissue Doppler imaging (A'; P-A'TDI); when prolonged, it might predict incident atrial fibrillation. METHODS: We measured P-A'TDI in outpatients with heart failure and sinus rhythm enrolled in the SICA-HF programme. RESULTS: P-A'TDI measured at the lateral mitral annulus was longer in patients with HF with reduced [LVEF<50%, N = 141; 126 (112-146) ms; P = 0.005] or preserved left ventricular ejection fraction [LVEF>50% and NT-proBNP > 125 ng/l, N = 71; 128 (108-145) ms; P = 0.026] compared to controls [N = 117; 120 (106-135) ms]. Increasing age, left atrial volume and PR interval were independently associated with prolonged P-A'TDI. During a median follow-up of 1251 (956-1602) days, 73 patients with heart failure died (N = 42) or developed atrial fibrillation (N = 31). In univariable analysis, P-A'TDI was associated with an increased risk of the composite outcome of death or atrial fibrillation, but only increasing log [NT-proBNP], age and more severe symptoms (NYHA III vs. I/II) were independently related to this outcome. Patients in whom both P-A'TDI and left atrial volume were above the median (127 ms and 64 ml, respectively) had the highest incidence of atrial fibrillation (hazard ratio 6.61, 95% CI 2.27-19.31; P < 0.001 compared with those with both P-A'TDI and LA volume below the median). CONCLUSION: Measuring P-A'TDI interval identifies patients with chronic heart failure at higher risk of dying or developing atrial fibrillation during follow-up.

Correction to: Is Cardiorespiratory Fitness Related to Cardiometabolic Health and All-Cause Mortality Risk in Patients with Coronary Heart Disease? A CARE CR Study.

The original article [1] contains an error in the presentation of Table 4.

Prevalence, pattern and clinical relevance of ultrasound indices of congestion in outpatients with heart failure.

AIMS: Even if treatment controls symptoms, patients with heart failure may still be congested. We aimed at assessing the prevalence and clinical relevance of congestion in outpatients with chronic heart failure. METHODS AND RESULTS: We recorded clinical and ultrasound [lung B-lines; inferior vena cava (IVC) diameter; internal jugular vein diameter before and after a Valsalva manoeuvre (JVD ratio)] features of congestion in heart failure patients during a routine check-up. Of 342 patients who attended, predominantly in New York Heart Association class I or II (n = 257; 75%), 242 (71%) had at least one feature of congestion, either clinical (n = 139; 41%) or by ultrasound (n = 199; 58%). Amongst patients (n = 203, 59%) clinically free of congestion, 31 (15%) had ≥ 14 B-lines, 57 (29%) had a dilated IVC (> 2.0 cm), 38 (20%) had an abnormal JVD ratio (< 4), 87 (43%) had at least one of these, and 27 (13%) had two or more. During a median follow-up of 234 (interquartile range 136-351) days, 60 patients (18%) died or were hospitalized for heart failure. In univariable analysis, each clinical and ultrasound measure of congestion was associated with increased risk but, in multivariable models, only higher N-terminal pro-B-type natriuretic peptide and IVC, and lower JVD ratio, were associated with the composite outcome. CONCLUSIONS: Many patients with chronic heart failure with few symptoms have objective evidence of congestion and this is associated with an adverse prognosis. Whether using these measures of congestion to guide management improves outcomes requires investigation.

The impact of heart failure and chronic obstructive pulmonary disease on mortality in patients presenting with breathlessness.

BACKGROUND: Differentiating heart failure from chronic obstructive pulmonary disease (COPD) in a patient presenting with breathlessness is difficult but may have implications for outcome. We investigated the prognostic impact of diagnoses of COPD and/or heart failure in consecutive patients presenting to a secondary care clinic with breathlessness. METHODS: In patients with left ventricular systolic dysfunction (LVSD) by visual estimation, N-terminal pro B-type natriuretic peptide (NTproBNP) levels and spirometry were evaluated (N = 4986). Heart failure was defined as either LVSD worse than mild (heart failure with reduced ejection fraction) or LVSD mild or better and raised NTproBNP levels (> 400 ng/L) (heart failure with normal ejection fraction). COPD was defined as forced expiratory volume in 1 s (FEV1) to forced vital capacity (FVC) ratio < 0.7. The primary outcome was all-cause mortality. RESULTS: 1764 (35%) patients had heart failure alone, 585 (12%) had COPD alone, 1751 (35%) had heart failure and COPD, and 886 (18%) had neither. Compared to patients with neither diagnosis, those with COPD alone [hazard ratio (HR) = 1.84 95% confidence interval (CI) 1.40-2.43], heart failure alone [HR = 4.40 (95% CI 3.54-5.46)] or heart failure and COPD [HR = 5.44 (95% CI 4.39-6.75)] had a greater risk of death. COPD was not associated with increased risk of death in patients with heart failure on a multivariable analysis. CONCLUSION: While COPD is associated with increased risk of death compared to patients with neither heart failure nor COPD, it has a negligible impact on prognosis amongst patients with heart failure.

Warm water immersion in patients with chronic heart failure: a pilot study : Shah immerse: HF.

BACKGROUND: Patients with chronic conditions, such as heart failure, swim regularly and most rehabilitation exercises are conducted in warm hydrotherapy pools. However, little is known about the acute effects of warm water immersion (WWI) on cardiac haemodynamics in patients with chronic heart failure (CHF). METHODS: Seventeen patients with CHF (NYHA I and II; mean age 67 years, 88% male, mean left ventricular ejection fraction 33%) and 10 age-matched normal subjects were immersed up to the neck in a hydrotherapy pool (33-35 °C). Cardiac haemodynamics were measured non-invasively, and echocardiography was performed at baseline, during WWI, 3 min after kicking in the supine position and after emerging. RESULTS: In patients with CHF, compared to baseline, WWI immediately increased stroke volume (SV, mean ± standard deviation; from 65 ± 21 to 82 ± 22 mL, p < 0.001), cardiac output (CO, from 4.4 ± 1.4 to 5.7 ± 1.6 L/min, p < 0.001) and cardiac index (CI, from 2.3 ± 0.6 to 2.9 ± 0.70 L/min/m², p < 0.001) with decreased systemic vascular resistance (from 1881 ± 582 to 1258 ± 332 dynes/s/cm5, p < 0.001) and systolic blood pressure (132 ± 21 to 115 ± 23 mmHg, p < 0.001). The haemodynamic changes persisted for 15 min of WWI. In normal subjects, compared to baseline, WWI increased SV (from 68 ± 11 to 80 ± 18 mL, p < 0.001), CO (from 5.1 ± 1.9 to 5.7 ± 1.8 L/min, p < 0.001) and CI (from 2.7 ± 0.9 to 2.9 ± 1.0 L/min/m², p < 0.001).In patients with CHF, compared to baseline, WWI caused an increase in left atrial volume (from 57 ± 44 to 72 ± 46 mL, p = 0.04), without any changes in left ventricular size or function or amino terminal pro B-type natriuretic peptide. CONCLUSIONS: In patients with CHF, WWI causes an acute increase in cardiac output and a fall in systemic vascular resistance. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov (Identifier: NCT02949544) https://clinicaltrials.gov/ct2/show/NCT02949544?cond=NCT02949544&rank=1 .

Is Cardiorespiratory Fitness Related to Cardiometabolic Health and All-Cause Mortality Risk in Patients with Coronary Heart Disease? A CARE CR Study.

BACKGROUND: Higher cardiorespiratory fitness (CRF) is associated with lower morbidity and mortality in patients with coronary heart disease (CHD). The mechanisms for this are not fully understood. A more favourable cardiometabolic risk factor profile may be responsible; however, few studies have comprehensively evaluated cardiometabolic risk factors in relation to CRF amongst patients with CHD. We aimed to explore differences in cardiometabolic risk and 5-year all-cause mortality risk in patients with CHD who have low, moderate, and high levels of CRF. METHODS: Patients with CHD underwent maximal cardiopulmonary exercise testing, echocardiogram, carotid intima-media thickness measurement, spirometry, and dual X-ray absorptiometry assessment. Full blood count, biochemical lipid profiles, high-sensitivity (hs) C-reactive protein, and NT-proBNP were analysed. Patients were defined as having low, moderate, or high CRF based on established prognostic thresholds. RESULTS: Seventy patients with CHD (age 63.1 ± 10.0 years, 86% male) were recruited. Patients with low CRF had a lower ventilatory anaerobic threshold, peak oxygen pulse, post-exercise heart rate recovery, and poor ventilatory efficiency. The low CRF group also had higher NT pro-BNP, hs-CRP, non-fasting glucose concentrations, and lower haemoglobin and haematocrit. Five-year mortality risk (CALIBER risk score) was also greatest in the lowest CRF group (14.9%). CONCLUSIONS: Practitioners should interpret low CRF as an important clinical risk factor associated with adverse cardiometabolic health and poor prognosis, study registry; www.researchregistry.com .

Non-invasive measurement of right atrial pressure by near-infrared spectroscopy: preliminary experience. A report from the SICA-HF study.

AIMS: To assess the clinical value of measuring right atrial pressure (RAP) using near-infrared spectroscopy (NIRS) in patients with chronic heart failure (CHF). METHODS AND RESULTS: RAP was measured non-invasively using NIRS over the external jugular vein (Venus 1000, Mespere LifeSciences, Canada) in ambulatory patients with CHF enrolled in the Studies Investigating Co-morbidities Aggravating Heart Failure (SICA-HF) programme. Comparing 243 patients with CHF (mean age 71 years; mean left ventricular ejection fraction (LVEF) 45%, median NT-proBNP 788 ng/L) to 49 controls (NT-proBNP ≤125 ng/L), RAP was 7 [interquartile range (IQR) 4-11] mmHg vs. 4 (IQR 3-8) mmHg (P < 0.001). Those with RAP ≥10 mmHg (n = 75) were older, had more severe clinical congestion and renal dysfunction, higher plasma NT-proBNP, larger left atrial volume, higher systolic pulmonary pressure and were more often in atrial fibrillation but their LVEF was similar to patients with lower RAP. During a median follow-up of 595 (IQR: 492-714) days, 49 patients (20%) died or were hospitalized for worsening CHF. Compared with patients with RAP ≤5 mmHg, those with RAP ≥10 mmHg had a greater risk of an event (hazard ratio 2.38, 95% confidence interval 1.19-4.75, P = 0.014). RAP measured by NIRS predicted outcome, competing with NT-proBNP in multivariable models. CONCLUSIONS: Measuring RAP using NIRS identifies ambulatory patients with CHF who have more severe congestion and a worse outcome. The device might be a useful objective method of monitoring RAP, especially for those inexperienced in eliciting physical signs or when measurement of natriuretic peptides is not immediately available.

Cardiac Dysfunction, Congestion and Loop Diuretics: their Relationship to Prognosis in Heart Failure.

BACKGROUND: Diuretics are the mainstay of treatment for congestion but concerns exist that they adversely affect prognosis. We explored whether the relationship between loop diuretic use and outcome is explained by the underlying severity of congestion amongst patients referred with suspected heart failure. METHOD AND RESULTS: Of 1190 patients, 712 had a left ventricular ejection fraction (LVEF) ≤50 %, 267 had LVEF >50 % with raised plasma NTproBNP (>400 ng/L) and 211 had LVEF >50 % with NTproBNP ≤400 ng/L; respectively, 72 %, 68 % and 37 % of these groups were treated with loop diuretics including 28 %, 29 % and 10 % in doses ≥80 mg furosemide equivalent/day. Compared to patients with cardiac dysfunction (either LVEF ≤50 % or NT-proBNP >400 ng/L) but not taking a loop diuretic, those taking a loop diuretic were older and had more clinical evidence of congestion, renal dysfunction, anaemia and hyponatraemia. During a median follow-up of 934 (IQR: 513-1425) days, 450 patients were hospitalized for HF or died. Patients prescribed loop diuretics had a worse outcome. However, in multi-variable models, clinical, echocardiographic (inferior vena cava diameter), and biochemical (NTproBNP) measures of congestion were strongly associated with an adverse outcome but not the use, or dose, of loop diuretics. CONCLUSIONS: Prescription of loop diuretics identifies patients with more advanced features of heart failure and congestion, which may account for their worse prognosis. Further research is needed to clarify the relationship between loop diuretic agents and outcome; imaging and biochemical measures of congestion might be better guides to diuretic dose than symptoms or clinical signs.

Experiences of medical students who are first in family to attend university.

CONTEXT: Students from backgrounds of low socio-economic status (SES) or who are first in family to attend university (FiF) are under-represented in medicine. Research has focused on these students' pre-admission perceptions of medicine, rather than on their lived experience as medical students. Such research is necessary to monitor and understand the potential perpetuation of disadvantage within medical schools. OBJECTIVES: This study drew on the theory of Bourdieu to explore FiF students' experiences at one Australian medical school, aiming to identify any barriers faced and inform strategies for equity. METHODS: Twenty-two FiF students were interviewed about their backgrounds, expectations and experiences of medical school. Interviews were recorded, transcribed and analysed thematically. Findings illustrate the influence and interaction of Bourdieu's principal forms of capital (social, economic and cultural) in FiF students' experiences. RESULTS: The absence of health professionals within participants' networks (social capital) was experienced as a barrier to connecting with fellow students and accessing placements. Financial concerns were common among interviewees who juggled paid work with study and worried about expenses associated with the medical programme. Finally, participants' 'medical student' status provided access to new forms of cultural capital, a transition that was received with some ambivalence by participants themselves and their existing social networks. CONCLUSIONS: This study revealed the gaps between the forms of capital valued in medical education and those accessible to FiF students. Admitting more students from diverse backgrounds is only one part of the solution; widening participation strategies need to address challenges for FiF students during medical school and should enable students to retain, rather than subdue, their existing, diverse forms of social and cultural capital. Embracing the diversity sought in admissions is likely to benefit student learning, as well as the communities graduates will serve. Change must ideally go beyond medical programmes to address medical culture itself.

Prognostic significance of ultrasound-assessed jugular vein distensibility in heart failure.

AIMS: Jugular venous distension is a classical sign of heart failure (HF) but it can be difficult to assess clinically. METHODS AND RESULTS: Outpatients with HF and control subjects were assessed. Internal jugular vein diameter (JVD) was measured using a linear high-frequency ultrasound probe (10 MHz) at rest, after a Valsalva manoeuvre and during deep inspiration. JVD ratio was calculated as the maximum diameter during Valsalva to that measured at rest. 311 patients (mean age 71 years, mean left ventricular EF 42%, median (IQR) amino-terminal pro-brain natriuretic peptide 979 (441-2007) ng/L) and 66 controls were included. JVD (median and IQR range) at rest was smaller in controls (0.16 (0.14-0.20) cm) than in patients with HF (0.23 (0.17-0.33) cm; p<0.001) but similar during Valsalva (1.03 (0.90-1.16) cm vs 1.08 (0.90-1.25) cm; p=0.28). Consequently, JVD ratio was greater in controls (6.3 (4.9-7.6)) than in patients (4.5 (2.9-6.1); p<0.001). During a median follow-up of 516 (IQR 335-622) days, 48 patients (15%) with HF died or were hospitalised for HF. In multivariable models, among clinical, echocardiographic or biochemical variables, only increasing NT-proBNP and ultrasound assessment of internal jugular vein were independently associated with prognosis. Comparing top and bottom tertiles of JVD ratio (2.3 (IQR 1.7-2.9) versus 6.8 (6.1-7.7)), the tertile with lower values had a 10-fold greater risk of an adverse event (HR 10.05, 95% CI 3.07 to 32.93). CONCLUSIONS: Ultrasound assessment of the internal jugular vein identifies outpatients with HF who have a higher risk of an adverse outcome. CLINICAL TRIAL REGISTRATION: NCT01872299.

The genomes of two key bumblebee species with primitive eusocial organization.

BACKGROUND: The shift from solitary to social behavior is one of the major evolutionary transitions. Primitively eusocial bumblebees are uniquely placed to illuminate the evolution of highly eusocial insect societies. Bumblebees are also invaluable natural and agricultural pollinators, and there is widespread concern over recent population declines in some species. High-quality genomic data will inform key aspects of bumblebee biology, including susceptibility to implicated population viability threats. RESULTS: We report the high quality draft genome sequences of Bombus terrestris and Bombus impatiens, two ecologically dominant bumblebees and widely utilized study species. Comparing these new genomes to those of the highly eusocial honeybee Apis mellifera and other Hymenoptera, we identify deeply conserved similarities, as well as novelties key to the biology of these organisms. Some honeybee genome features thought to underpin advanced eusociality are also present in bumblebees, indicating an earlier evolution in the bee lineage. Xenobiotic detoxification and immune genes are similarly depauperate in bumblebees and honeybees, and multiple categories of genes linked to social organization, including development and behavior, show high conservation. Key differences identified include a bias in bumblebee chemoreception towards gustation from olfaction, and striking differences in microRNAs, potentially responsible for gene regulation underlying social and other traits. CONCLUSIONS: These two bumblebee genomes provide a foundation for post-genomic research on these key pollinators and insect societies. Overall, gene repertoires suggest that the route to advanced eusociality in bees was mediated by many small changes in many genes and processes, and not by notable expansion or depauperation.

Development of a Human Model for the Study of Effects of Hypoxia, Exercise, and Sildenafil on Cardiac and Vascular Function in Chronic Heart Failure.

BACKGROUND: Pulmonary hypertension is associated with poor outcome in patients with chronic heart failure (CHF) and may be a therapeutic target. Our aims were to develop a noninvasive model for studying pulmonary vasoreactivity in CHF and characterize sildenafil's acute cardiovascular effects. METHODS AND RESULTS: In a crossover study, 18 patients with CHF participated 4 times [sildenafil (2 × 20 mg)/or placebo (double-blind) while breathing air or 15% oxygen] at rest and during exercise. Oxygen saturation (SaO2) and systemic vascular resistance were recorded. Left and right ventricular (RV) function and transtricuspid systolic pressure gradient (RVTG) were measured echocardiographically. At rest, hypoxia caused SaO2 (P = 0.001) to fall and RVTG to rise (5 ± 4 mm Hg; P = 0.001). Sildenafil reduced SaO2 (-1 ± 2%; P = 0.043), systemic vascular resistance (-87 ± 156 dyn·s·cm; P = 0.034), and RVTG (-2 ± 5 mm Hg; P = 0.05). Exercise caused cardiac output (2.1 ± 1.8 L/min; P < 0.001) and RVTG (19 ± 11 mm Hg; P < 0.0001) to rise. The reduction in RVTG with sildenafil was not attenuated by hypoxia. The rise in RVTG with exercise was not substantially reduced by sildenafil. CONCLUSIONS: Sildenafil reduces SaO2 at rest while breathing air, this was not exacerbated by hypoxia, suggesting increased ventilation-perfusion mismatching due to pulmonary vasodilation in poorly ventilated lung regions. Sildenafil reduces RVTG at rest and prevents increases caused by hypoxia but not by exercise. This study shows the usefulness of this model to evaluate new therapeutics in pulmonary hypertension.

Finding the missing honey bee genes: lessons learned from a genome upgrade.

BACKGROUND: The first generation of genome sequence assemblies and annotations have had a significant impact upon our understanding of the biology of the sequenced species, the phylogenetic relationships among species, the study of populations within and across species, and have informed the biology of humans. As only a few Metazoan genomes are approaching finished quality (human, mouse, fly and worm), there is room for improvement of most genome assemblies. The honey bee (Apis mellifera) genome, published in 2006, was noted for its bimodal GC content distribution that affected the quality of the assembly in some regions and for fewer genes in the initial gene set (OGSv1.0) compared to what would be expected based on other sequenced insect genomes. RESULTS: Here, we report an improved honey bee genome assembly (Amel_4.5) with a new gene annotation set (OGSv3.2), and show that the honey bee genome contains a number of genes similar to that of other insect genomes, contrary to what was suggested in OGSv1.0. The new genome assembly is more contiguous and complete and the new gene set includes ~5000 more protein-coding genes, 50% more than previously reported. About 1/6 of the additional genes were due to improvements to the assembly, and the remaining were inferred based on new RNAseq and protein data. CONCLUSIONS: Lessons learned from this genome upgrade have important implications for future genome sequencing projects. Furthermore, the improvements significantly enhance genomic resources for the honey bee, a key model for social behavior and essential to global ecology through pollination.