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Background Fluid overload in patients undergoing hemodialysis contributes to cardiovascular morbidity and mortality. There is a global trend to lower dialysate sodium with the goal of reducing fluid overload. Methods To investigate whether lower dialysate sodium during hemodialysis reduces left ventricular mass, we conducted a randomized trial in which patients received either low-sodium dialysate (135 mM) or conventional dialysate (140 mM) for 12 months. We included participants who were aged >18 years old, had a predialysis serum sodium ≥135 mM, and were receiving hemodialysis at home or a self-care satellite facility. Exclusion criteria included hemodialysis frequency >3.5 times per week and use of sodium profiling or hemodiafiltration. The main outcome was left ventricular mass index by cardiac magnetic resonance imaging. Results The 99 participants had a median age of 51 years old; 67 were men, 31 had diabetes mellitus, and 59 had left ventricular hypertrophy. Over 12 months of follow-up, relative to control, a dialysate sodium concentration of 135 mmol/L did not change the left ventricular mass index, despite significant reductions at 6 and 12 months in interdialytic weight gain, in extracellular fluid volume, and in plasma B-type natriuretic peptide concentration (ratio of intervention to control). The intervention increased intradialytic hypotension (odds ratio [OR], 7.5; 95% confidence interval [95% CI], 1.1 to 49.8 at 6 months and OR, 3.6; 95% CI, 0.5 to 28.8 at 12 months). Five participants in the intervention arm could not complete the trial because of hypotension. We found no effect on health-related quality of life measures, perceived thirst or xerostomia, or dietary sodium intake. Conclusions Dialysate sodium of 135 mmol/L did not reduce left ventricular mass relative to control, despite improving fluid status. Clinical trial registry name and registration number The Australian New Zealand Clinical Trials Registry, ACTRN12611000975998.

BackgroundIn April 2016 Greater Manchester gained control of its health and social care budget, a devolution that aimed to reduce health inequities both within Greater Manchester and between Greater Manchester and the rest of the country.AimTo describe the relationship between practice location deprivation and primary care funding and care quality measurements in the first year of Greater Manchester devolution (2016/2017).Design and settingCross-sectional analysis of 472 general practices in Greater Manchester in England.MethodFinancial data for each general practice were linked to the area deprivation of the practice location, as measured by the 2015 Index of Multiple Deprivation. Practices were categorised into five quintiles relative to national deprivation. NHS Payments data and indicators of care quality were compared across social deprivation quintiles.ResultsPractices in areas of greater deprivation did not receive additional funding per registered patient. Practices in less deprived quintiles received higher National Enhanced Services payments from NHS England than practices in the most deprived quintile. A trend was observed towards funding to more deprived practices being supported by Local Enhanced Service payments from clinical commissioning groups, but these represent a small proportion of overall practice income. Practices in less deprived areas had better care quality measurements according to Quality and Outcomes Framework achievement and Care Quality Commission ratings.ConclusionFollowing devolution, primary care practices in Greater Manchester are still reliant on funding from national funding schemes, which poorly reflect its deprivation. The devolved administration’s ability to address health inequities at the primary care level seems uncertain.

BackgroundCOVID-19 has led to rapid and widespread use of remote consultations in general practice, but the health inequalities impact remains unknown.AimTo explore the impact of remote consultations in general practice, compared to face-to-face consultations, on utilisation and clinical outcomes across socioeconomic and disadvantaged groups.Design & settingSystematic review.MethodThe authors undertook an electronic search of MEDLINE, EMBASE, and Web of Science from inception to June 2020. The study included studies that compared remote consultations to face-to-face consultations in primary care and reported outcomes by PROGRESS Plus criteria. Risk of bias was assessed using ROBINS-I. Data were synthesised narratively.ResultsBased on 13 studies that explored telephone and internet-based consultations, this review found that telephone consultations were used by younger people of working age, the very old, and non-immigrants, with internet-based consultations more likely to be used by younger people. Women consistently used more remote forms of consulting than men. Socioeconomic and ethnicity findings were mixed, with weak evidence that patients from more affluent areas were more likely to use internet-based communication. Remote consultations appeared to help patients with opioid dependence remain engaged with primary care. No studies reported on the impact on quality of care or clinical outcomes.ConclusionRemote consultations in general practice are likely to be used more by younger, working people, non-immigrants, older patients, and women, with internet-based consultations more by younger, affluent, and educated groups. Widespread use of remote consultations should be treated with caution until the inequalities impact on clinical outcomes and quality of care is known.

As with most diseases, COVID-19 has hit the poorest and most vulnerable in society the hardest. In the UK, people living in the most deprived areas have twice the mortality rate from COVID-19 as those in the least deprived areas. They face increased exposure to the disease and have been most affected by the wider unintended consequences of social distancing measures and the economic downturn. Furthermore, the disproportionate impact of the pandemic on people from black, Asian, and minority ethnic (BAME) communities is partly explained by socioeconomic disadvantage. And all of this is in the context of a decade of widening social and health inequalities. Yet, through this adversity, there is hope and opportunity: the pandemic offers a ‘compassion window’ of societal, political, and professional awareness and willingness to act, and general practice has a key role to play in putting equity at the heart of our health system renewal. Throughout the pandemic there has rightly been …

Growing demands on primary care services have led to policymakers promoting video consultations (VCs) to replace routine face-to-face consultations (FTFCs) in general practice.To explore the content, quality, and patient experience of VC, telephone (TC), and FTFCs in general practice.Comparison of audio-recordings of follow-up consultations in UK primary care.Primary care clinicians were provided with video-consulting equipment. Participating patients required a smartphone, tablet, or computer with camera. Clinicians invited patients requiring a follow-up consultation to choose a VC, TC, or FTFC. Consultations were audio-recorded and analysed for content and quality. Participant experience was explored in post-consultation questionnaires. Case notes were reviewed for NHS resource use.Of the recordings, 149/163 were suitable for analysis. VC recruits were younger, and more experienced in communicating online. FTFCs were longer than VCs (mean difference +3.7 minutes, 95% confidence interval [CI] = 2.1 to 5.2) or TCs (+4.1 minutes, 95% CI = 2.6 to 5.5). On average, patients raised fewer problems in VCs (mean 1.5, standard deviation [SD] 0.8) compared with FTFCs (mean 2.1, SD 1.1) and demonstrated fewer instances of information giving by clinicians and patients. FTFCs scored higher than VCs and TCs on consultation-quality items.VC may be suitable for simple problems not requiring physical examination. VC, in terms of consultation length, content, and quality, appeared similar to TC. Both approaches appeared less 'information rich' than FTFC. Technical problems were common and, though patients really liked VC, infrastructure issues would need to be addressed before the technology and approach can be mainstreamed in primary care.

We describe a broad class of problems, called “uncompromising problems,” which are characterized by the requirement that solutions must perform optimally on each of many test cases. Many of the problems that have long motivated genetic programming research, including the automation of many traditional programming tasks, are uncompromising. We describe and analyze the recently proposed “lexicase” parent selection algorithm and show that it can facilitate the solution of uncompromising problems by genetic programming. Unlike most traditional parent selection techniques, lexicase selection does not base selection on a fitness value that is aggregated over all test cases; rather, it considers test cases one at a time in random order. We present results comparing lexicase selection to more traditional parent selection methods, including standard tournament selection and implicit fitness sharing, on four uncompromising problems: 1) finding terms in finite algebras; 2) designing digital multipliers; 3) counting words in files; and 4) performing symbolic regression of the factorial function. We provide evidence that lexicase selection maintains higher levels of population diversity than other selection methods, which may partially explain its utility as a parent selection algorithm in the context of uncompromising problems.

After the publication of our paper Dunlop et al. “Rationale and design of the Sodium Lowering In Dialysate (SoLID) trial: a randomised controlled trial of low versus standard dialysate sodium concentration during hemodialysis for regression of left ventricular mass”, we became aware of further data correlating left ventricular (LV) mass index at baseline and their correpsonding mass at 12 months, using cardiac margnetic resonanace imaging (MRI) in patients on hemodialysis. The original published sample size for the SoLID trial of 118 was a conservative estimate, calculated using analysis of covariance and a within person Pearson’s correlation for LV mass index of 0.75. New data communicated to the SoLID trial group has resulted in re-calcuation of the sample size, based upon a within person Pearson’s correlation of 0.8 but otherwise unchanged assumptions. As a result, the SoLID trial will now recruit 96 participants.

Background The Sodium Lowering in Dialysate (SoLID) trial is an ongoing a multi-center, prospective, randomised, single-blind (assessor), controlled, parallel assignment clinical trial, enrolling 96 home and self-care hemodialysis (HD) patients from 7 centers in New Zealand. The trial will evaluate the hypothesis that lower dialysate [Na+] during HD results in lower left ventricular (LV) mass. Since it’s inception, observational evidence has suggested increased mortality risk with lower dialysate [Na+], possibly due to exacerbation of intra-dialytic hypotension and subsequent myocardial micro-injury. The Myocardial Micro-injury and Cardiac Remodeling Extension Study in the Sodium Lowering In Dialysate Trial (Mac-SoLID study) aims to determine whether lower dialysate [Na+] results in (i) increased levels of high-sensitivity Troponin T (hsTnT), a well-established marker of intra-dialytic myocardial micro-injury in HD populations, and (ii) increased fixed LV segmental wall motion abnormalities, a marker of recurrent myocardial stunning and micro-injury, and (iii) detrimental changes in LV geometry due to maladaptive homeostatic mechanisms. Methods/design The SoLID trial and the Mac-SoLID study are funded by the Health Research Council of New Zealand. Key exclusion criteria: patients who dialyse > 3.5 times per week, pre-dialysis serum sodium

Background The current literature recognises that left ventricular hypertrophy makes a key contribution to the high rate of premature cardiovascular mortality in dialysis patients. Determining how we might intervene to ameliorate left ventricular hypertrophy in dialysis populations has become a research priority. Reducing sodium exposure through lower dialysate sodium may be a promising intervention in this regard. However there is clinical equipoise around this intervention because the benefit has not yet been demonstrated in a robust prospective clinical trial, and several observational studies have suggested sodium lowering interventions may be deleterious in some dialysis patients. Methods/design The Sodium Lowering in Dialysate (SoLID) study is funded by the Health Research Council of New Zealand. It is a multi-centre, prospective, randomised, single-blind (outcomes assessor), controlled parallel assignment 3-year clinical trial. The SoLID study is designed to study what impact low dialysate sodium has upon cardiovascular risk in dialysis patients. The study intends to enrol 118 home hemodialysis patients from 6 sites in New Zealand over 24 months and follow up each participant over 12 months. Key exclusion criteria are: patients who dialyse more frequently than 3.5 times per week, pre-dialysis serum sodium of Discussion The SoLID study is designed to clarify the effect of low dialysate sodium upon the cardiovascular outcomes of dialysis patients. The study results will provide much needed information about the efficacy of a cost effective, economically sustainable solution to a condition which is curtailing the lives of so many dialysis patients. Trial registration Australian and New Zealand Clinical Trials Registry number: ACTRN12611000975998

Language can impact emotion, even when it makes no reference to emotion states. For example, reading sentences with positive meanings (“The water park is refreshing on the hot summer day”) induces patterns of facial feedback congruent with the sentence emotionality (smiling), whereas sentences with negative meanings induce a frown. Moreover, blocking facial afference with botox selectively slows comprehension of emotional sentences. Therefore, theories of cognition should account for emotion-language interactions above the level of explicit emotion words, and the role of peripheral feedback in comprehension. For this special issue exploring frontiers in the role of the body and environment in cognition, we propose a theory in which facial feedback provides a context-sensitive constraint on the simulation of actions described in language. Paralleling the role of emotions in real-world behavior, our account proposes that (1) facial expressions accompany sudden shifts in wellbeing as described in language; (2) facial expressions modulate emotional action systems during reading; and (3) emotional action systems prepare the reader for an effective simulation of the ensuing language content. To inform the theory and guide future research, we outline a framework based on internal models for motor control. To support the theory, we assemble evidence from diverse areas of research. Taking a functional view of emotion, we tie the theory to behavioral and neural evidence for a role of facial feedback in cognition. Our theoretical framework provides a detailed account that can guide future research on the role of emotional feedback in language processing, and on interactions of language and emotion. It also highlights the bodily periphery as relevant to theories of embodied cognition.

James Matheson (1796–1878) became a leading taipan, with significant influence and power in Hong Kong. When this pamphlet was published, in 1836, he was still trading from Canton (Guangzhou) and, following the abolition of the East India Company's monopoly on trade with China, appealed to the British government to pressure the Chinese to lift the severe restrictions on trading. He suggests that despite the efforts of the merchants, China refuses to acknowledge the law of nations, to trade fairly, and as such has 'long since surrendered her rights and is no longer in a position to enforce them'. Matheson's personal appeal to the Duke of Wellington was rebuffed, but his business partner, William Jardine, later persuaded Lord Palmerston to adopt a tougher approach, which ultimately led to the First Opium War. This is a powerful and provocative text: a defence of both free trade and an aggressive foreign policy.

Andrew Reed (1787–1862) was a Congregational Minister and one of the leading philanthropists of his day, fund-raising for and founding a number of orphanages and asylums. In 1834, he and fellow Congregational Minister James Matheson (1766–1840) were sent to the Congregational churches of the United States, in order to promote peace and friendship between the two communities. This two-volume 1835 work consists of thirty-nine letters in which the authors recount their journey, and their meetings with their fellow Congregationalists. They visited a large number of cities, mostly on the Eastern Seaboard, and made one excursion to Canada. Volume 2 tells of the many different communities that Reed and Matheson encounter in America, and the focus is mostly on theological and educational issues. They approve of female academies, asking rhetorically, 'why should not our daughters, equally with our sons, possess the advantages, which these institutions … so readily supply?'.

A case of a 44-yr-old Maori female presenting with chronic renal failure due to karyomegalic interstitial nephritis is reported. To our knowledge, this is the first instance this disorder has been reported in a New Zealand Maori. Karyomegalic interstitial nephritis is a rare cause of progressive renal failure, which may be familial, and is frequently associated with a history of recurrent respiratory infections. The urine in this case contained large, pleomorphic cells, mimicking carcinoma. The case therefore illustrates a rare cause of chronic renal failure, and presents an important diagnostic pitfall in the practice of urine cytopathology.