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Background Information on clinical outcomes of coronavirus disease 19 (COVID-19) infection in patients with adrenal disorders is scarce. Methods A collaboration between the European Society of Endocrinology (ESE) Rare Disease Committee and European Reference Network on Rare Endocrine Conditions via the European Registries for Rare Endocrine Conditions allowed the collection of data on 64 cases (57 adrenal insufficiency (AI), 7 Cushing’s syndrome) that had been reported by 12 centres in 8 European countries between January 2020 and December 2021. Results Of all 64 patients, 23 were males and 41 females (13 of those children) with a median age of 37 and 51 years. In 45/57 (95%) AI cases, COVID-19 infection was confirmed by testing. Primary insufficiency was present in 45/57 patients; 19 were affected by Addison’s disease, 19 by congenital adrenal hyperplasia and 7 by primary AI (PAI) due to other causes. The most relevant comorbidities were hypertension (12%), obesity (n = 14%) and diabetes mellitus (9%). An increase by a median of 2.0 (IQR 1.4) times the daily replacement dose was reported in 42 (74%) patients. Two patients were administered i.m. injection of 100 mg hydrocortisone, and 11/64 were admitted to the hospital. Two patients had to be transferred to the intensive care unit, one with a fatal outcome. Four patients reported persistent SARS-CoV-2 infection, all others complete remission. Conclusion This European multicentre questionnaire is the first to collect data on the outcome of COVID-19 infection in patients with adrenal gland disorders. It suggests good clinical outcomes in case of duly dose adjustments and emphasizes the importance of patient education on sick day rules.

There is a lack of affordable and acceptable sanitation solutions for dense, low-income urban settlements. One option that has been proposed is container-based sanitation, where a sealed cartridge installed in a free-standing toilet is regularly changed and adequately separates users from their excreta. Though container-based toilets are considered a safely managed sanitation solution that meets the Sustainable Development Goal for sanitation, little is known about user experiences to inform how such a solution should be viewed by governments. We conducted a longitudinal prospective cohort study of changes in objective and subjective measures of sanitation quality due to the Clean Team Ghana (CTG) container- based toilet service in Kumasi, Ghana from June to December 2019. We collected data immediately prior to installation of a toilet and 10 weeks afterwards for 292 customers. Most initially used public toilets with good structural quality, but sometimes had poor cleanliness, a lack of handwashing facilities, and required a 14.3 minute mean round trip time to use. The evaluation found that CTG delivers a high-quality service that positively impacts the quality of life of CTG customers, as well as saving them money, reducing gender gaps in quality of life, and addressing the needs of those with physical disabilities. Satisfaction with CTG toilet and service characteristics was high, with the largest increases for satisfaction with smell, comfort, disgust, and privacy. Women in particular were positively impacted both for explicitly gendered indicators like the ability to practice menstrual hygiene management, and other indicators where women scored lower than men at baseline, including ease of access, ease of use, and cleanliness. Use of the service also benefitted those who had been unable to use a toilet for physical or social reasons beforehand. Problems with the CTG service, such as leaking, filling, smelling, or not being replaced as scheduled, were reported by fewer than 10% of customers. While one product or service does not fit the needs of all customers, this evaluation supports the growing body of evidence that container-based sanitation provides a service valued by users and acceptable to policymakers in dense urban settlements.

Background Hormone therapy in transgender individuals may impact processes that lead to changes in biochemical analytes, and therefore reference intervals. Currently, few reference interval studies are available for the transgender population. We determined biochemical reference intervals for transgender individuals receiving hormone therapy. Methods Our retrospective, laboratory-based, observational study included healthy transgender males ( N = 24) and transgender females ( N = 84) on hormone therapy. Various biochemical reference intervals were established for each cohort and compared to their cisgender counterparts. Results We detected significant differences in reference intervals for sodium, 139–142 mmol/L vs. 136–145 mmol/L when comparing transgender males (TM) with cisgender males (CM). The following significant changes in upper reference limits (URL) for TM versus CM were detected, ALP (URL: 96 U/L vs. 128 U/L), GGT (URL: 27 U/L vs. 67 U/L) and testosterone (URL: 46.7 nmol/L vs. 29.0 nmol/L), respectively. Moreover, when comparing transgender female (TF) to cisgender female (CF), significant differences in creatinine (URL: 117 μmol/L vs. 90 μmol/L), albumin (lower reference limit: 41 g/L, vs. 35 g/L), AST (URL: 50 U/L vs. 35 U/L), ALP (URL: 118 U/L vs. 98 U/L) and oestradiol (URL: 934 pmol/L vs. 213 pmol/L) were noted, respectively. Significantly higher LDL-C was observed for TM on hormone treatment, compared to baseline (2.9 mmol/L vs. 2.2 mmol/L, p Conclusions Biochemical results for TM and TF receiving hormone therapy can be evaluated against our transgender-specific reference intervals for some analytes, while others can be compared to their identified gender reference intervals.

Background Insulinomas are rare clinical entities, but concurrent diabetes mellitus is even more uncommon, and the combination is easily missed. Recurrent hypoglycemia could be misconstrued as improved glycemic control. We present an unusual patient with type 2 diabetes and neuroglycopenia, with apparent improved glycemic control due to an insulinoma. Case presentation A 54-year-old mixed ancestry man with a positive family history of type 2 diabetes mellitus was diagnosed with type 2 diabetes mellitus and hypertension 8 years prior to admission. He presented with episodes of abnormal behavior and hypoglycemia. Inappropriately high insulin and C-peptide concentrations were identified at the time of hypoglycemia. Despite poor adherence to his diabetic treatment, he had no target organ damage relating to diabetes, and his hemoglobin A1c (HbA1c) was 5.3%. A diagnosis of insulinoma was made, and he was started on diazoxide, with endoscopic ultrasound revealing a possible lesion in the pancreatic tail measuring 12 mm × 12 mm. A fine-needle aspiration biopsy could not be performed due to overlying splenic arteries and the risk of vascular perforation. An intraoperative ultrasound confirmed a 15 mm × 10 mm tumor in the pancreatic tail, necessitating a partial pancreatectomy and splenectomy, which were curative. A well-differentiated intermediate grade 2 pancreatic neuroendocrine tumor producing insulin was confirmed on histopathology. Conclusions Recurrent, progressive hypoglycemia and improved glycemic control in a diabetic, without an alternative explanation, may suggest an insulinoma. Insulinomas that exist with type 1 diabetes mellitus, particularly malignant insulinomas, must have escaped autoimmune attack through lack of autoantigen expression. Computed tomography on its own may be insufficiently sensitive for diagnosis of insulinomas, whereas endoscopic and intraoperative ultrasonography may improve the identification of the culprit lesion.

Over 3 billion years, photosynthetic algae have evolved complex uses for cellulose, the most abundant polymer worldwide. A major cell-wall component of lignocellulosic plants, seaweeds, microalgae, and bacteria, cellulose can be processed to nanocellulose, a promising nanomaterial with novel properties. The structural diversity of macro- and microalgal nanocelluloses opens opportunities to couple low-impact biomass production with novel, green-chemistry processing to yield valuable, sustainable nanomaterials for a multitude of applications ranging from novel wound dressings to organic solar cells. We review the origins of algal cellulose and the applications and uses of nanocellulose, and highlight the potential for microalgae as a nanocellulose source. Given the limited state of current knowledge, we identify research challenges and strategies to help to realise this potential.

BackgroundAlthough theory-driven evaluations should have empirical components, few evaluations of public health interventions quantitatively test the causal model made explicit in the theory of change (ToC). In the context of a shared sanitation trial (MapSan) in Maputo, Mozambique, we report findings of a quantitative process evaluation assessing intervention implementation, participant response and impacts on hypothesised intermediary outcomes on the pathway to trial health outcomes. We examine the utility of path analysis in testing intervention theory using process indicators from the intervention’s ToC.MethodsProcess data were collected through a cross-sectional survey of intervention and control compounds of the MapSan trial > 24-months post-intervention, sampling adult residents and compound leaders. Indicators of implementation fidelity (dose received, reach) and participant response (participant behaviours, intermediary outcomes) were compared between trial arms. The intervention’s ToC (formalised post-intervention) was converted to an initial structural model with multiple alternative pathways. Path analysis was conducted through linear structural equation modelling (SEM) and generalised SEM (probit model), using a model trimming process and grouped analysis to identify parsimonious models that explained variation in outcomes, incorporating demographics of respondents and compounds.ResultsAmong study compounds, the MapSan intervention was implemented with high fidelity, with a strong participant response in intervention compounds: improvements were made to intermediary outcomes related to sanitation ‘quality’ – latrine cleanliness, maintenance and privacy – but not to handwashing (presence of soap / soap residue). These outcomes varied by intervention type: single-cabin latrines or multiple-cabin blocks (designed for > 20 users). Path analysis suggested that changes in intermediary outcomes were likely driven by direct effects of intervention facilities, with little contribution from hygiene promotion activities nor core elements expected to mediate change: a compound sanitation committee and maintenance fund. A distinct structural model for two compound size subgroups (≤ 20 members vs. > 20 members) explained differences by intervention type, and other contextual factors influenced specific model parameters.ConclusionsWhile process evaluation found that the MapSan intervention achieved sufficient fidelity and participant response, the path analysis approach applied to test the ToC added to understanding of possible ‘mechanisms of change’, and has value in disentangling complex intervention pathways.Trial registrationMapSan trial registration:NCT02362932Feb-13-2015.

Shared sanitation is not currently accepted within the international normative definitions of “basic” or “safely managed” sanitation. We argue that pro-poor government strategies and investment plans must include high-quality shared sanitation as an intermediate step in some densely populated urban areas. User experience must be considered in establishing the definition of high quality. We call for additional research on effective interventions to reach these quality standards and for the development of rigorous measures applicable to global monitoring.

Background The burden and management of primary adrenal insufficiency (PAI) in Africa have not been well documented. We aimed to identify specific disease characteristics, patient demographics, and patterns of clinical management in established PAI in Africa. Methods An online survey of physicians’ experience relating to PAI. Results There were 1334 responses received, 589 were complete, and 332 respondents reported managing patients with hypoadrenalism. The described responses were related to a calculated pool of 5787 patients with hypoadrenalism (2746 females, 3041 males), of whom 2302 had PAI. The likely causes of PAI in Sub-Saharan Africa (SSA) vs the Middle East and North Africa (MENA) regions included autoimmune disease (20% vs 60.3%; P P P P P = 0.328), s-cortisol 49.4 % vs 26.7% (P = 0.004), s-ACTH 55.7% vs 53.3% (P = 0.217), and adrenal CT scans 52.4% vs 31.8% (P = 0.017) in the SSA and MENA region, respectively. Across the entire cohort, the overall hydrocortisone use and extrapolated proportion of synacthen use were 59.4% and 50.7%, respectively. Conclusions Through the perception and practice of healthcare professionals, we identified significant challenges in the diagnosis and management of PAI which may herald high mortality. Differences between regions may reflect the allocation of healthcare resources.

Permanganate (PM) has shown to be able to oxidize a range of organic contaminants including perfluorooctane sulfonate (PFOS). However, mechanisms of PFOS removal by PM have been questioned. To provide clarity to what may be happening to PFOS in PM systems, here we evaluated the ability of PM on PFOS destruction by conducting studies similar to previous studies that reported PFOS destruction which included PM solutions and PM combined with persulfate (PS). We also evaluated if addition of various soluble catalysts could enhance PM's potential to breakdown PFOS. We observed no PFOS destruction by PM. We also show that the F- and SO42- generation reported in a published study as evidence that PM was breaking bonds in PFOS were found below or not significantly higher than reported limits of quantitation and that SO42- impurities in technical PM approach the reported SO42- levels. For PM-PS systems, heterogeneous PFOS distribution was observed when subsampling reaction vessels at different depths and "salting-out" of PFOS was evident. In addition, subsequent sonication and filtering of the samples led to the apparent disappearance of most of the PFOS, which was an artifact arising from the behavior of PFOS aggregates or potential hemi-micelle formation. Given these findings, addition of salts may have application for collecting or concentrating PFOS and other PFAAs in a remediation or water treatment strategy.

IntroductionDomestic hand hygiene could prevent over 500,000 attributable deaths per year, but 6 in 10 people in least developed countries (LDCs) do not have a handwashing facility with soap and water available at home. We estimated the economic costs of universal access to basic hand hygiene services in household settings in 46 LDCs. MethodsOur model combines quantities of households with no handwashing facility (HWF) and prices of promotion campaigns, HWFs, soap, and water. For quantities, we used estimates from the WHO/UNICEF Joint Monitoring Programme. For prices, we collated data from recent impact evaluations and electronic searches. Accounting for inflation and purchasing power, we calculated costs over 2021-2030, and estimated total cost probabilistically using Monte Carlo simulation. ResultsAn estimated US$ 12.2 - 15.3 billion over 10 years is needed for universal hand hygiene in household settings in 46 LDCs. The average annual cost of hand hygiene promotion is $334 million (24% of annual total), with a further $233 million for top-up promotion (17%). Together, these promotion costs represent $0.47 annually per head of LDC population. The annual cost of HWFs, a purpose-built drum with tap and stand, is $174 million (13%). The annual cost of soap is $497 million (36%), and water $127 million (9%). ConclusionThe annual cost of behaviour change promotion to those with no handwashing facility represents 4.7% of median government health expenditure in LDCs, and 1% of their annual aid receipts. These costs could be covered by mobilising resources from across government and partners, and could be reduced by harnessing economies of scale and integrating hand hygiene with other behaviour change campaigns where appropriate. Innovation is required to make soap more affordable and available for the poorest households. Summary boxO_ST_ABSWhat is already known?C_ST_ABSO_LIUnderstanding resource requirements is important for planning, but data on the costs of improving domestic hand hygiene are scarce. C_LIO_LIWhile a 2016 study estimated the global cost of drinking water, sanitation and hygiene, it did not report hygiene-specific estimates of recurrent or total cost, nor did it describe the assumed promotion intervention and handwashing facility or consider alternatives to them. C_LI What are the new findings?O_LIThe total economic cost over 10 years is US$ 12.2 - 15.3 billion, of which $4.9 - 6.6 billion (42%) is for behaviour change promotion interventions. C_LIO_LIThe remainder is for facilities and supplies, with soap the biggest cost category (36%) followed by handwashing facilities (13%) and water (9%). C_LIO_LIThe facility and supply costs per household comprise an initial investment in a handwashing facility (lasting 5 years) at a median of US$ 17, accompanied by an annual cost of $17 for soap and $5 for water (Figure 1). C_LI O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=86 SRC="FIGDIR/small/21262011v1_fig1.gif" ALT="Figure 1"> View larger version (12K): org.highwire.dtl.DTLVardef@1c02d4org.highwire.dtl.DTLVardef@fde3bforg.highwire.dtl.DTLVardef@73228borg.highwire.dtl.DTLVardef@e0f9dc_HPS_FORMAT_FIGEXP M_FIG O_FLOATNOFigure 1:C_FLOATNO Distribution of key input price variables in international dollars (I$) * The base case promotion intervention includes one-to-one activities, group activities and mass media. The alternative case excludes one-to-one activities. This figure presents results in I$ - the median US$ prices per household after converting to local purchasing power are $33.9 for base case promotion, $16.6 for HWF, $17.1 for soap expenditure, and $17.2 for alternative case promotion. Median annual expenditure per household on water for handwashing was $5.7 in rural areas and $4.0 in urban areas. The US$ median for the home-made HWF considered under sensitivity analysis was $1.2. C_FIG What do the new findings imply?O_LIThe annual cost of behaviour change promotion to those with no handwashing facility represents 4.7% of median government health expenditure in LDCs. C_LIO_LIOn top of this, investments in infrastructure and supplies are required. Soap in particular is a substantial and recurrent cost, which may be unaffordable for the poorest households. C_LIO_LIPromotion costs could be covered by mobilising resources from across government and partners, and could be reduced by harnessing economies of scale and integrating hand hygiene with other behaviour change campaigns where appropriate. C_LI

Climate resilient development has become the new paradigm for sustainable development influencing theory and practice across all sectors globally—gaining particular momentum in the water sector, since water security is intimately connected to climate change. Climate resilience is increasingly recognised as being inherently political, yet efforts often do not sufficiently engage with context-specific socio-ecological, cultural and political processes, including structural inequalities underlying historically produced vulnerabilities. Depoliticised approaches have been shown to pose barriers to concerted and meaningful change. In this article, world-leading water specialists from academic and practitioner communities reflect on, and share examples of, the importance of keeping people and politics at the centre of work on climate resilient water security. We propose a roadmap to meaningfully engage with the complex politics of climate resilient water security. It is critical to re-politicise climate resilience to enable efforts towards sustainable development goal 6—clean water and sanitation for all.

Diarrhoeal disease remains a leading cause of mortality and morbidity worldwide. Cholera alone is estimated to cause 95,000 deaths per year, most of which occur in endemic settings with inadequate water access. Whilst a global strategy to eliminate cholera by 2030 calls for investment in improved drinking water services, there is limited rigorous evidence for the impact of improved water supply on endemic cholera transmission in low-income urban settings. Our protocol is designed to deliver a pragmatic health impact evaluation of a large-scale water supply intervention in Uvira (Democratic Republic of the Congo), a cholera transmission hotspot.A stepped-wedge cluster randomised trial (SW-CRT) was designed to evaluate the impact of a large-scale drinking water supply intervention on cholera incidence among the 280,000 inhabitants of Uvira. The city was divided into 16 clusters, where new community and household taps will be installed following a randomised sequence over a transition period of up to 8 weeks in each cluster. The primary trial outcomes are the monthly incidence of "confirmed" cholera cases (patients testing positive by rapid detection kit) and of "suspected" cholera cases (patients admitted to the cholera treatment centre). Concurrent process and economic evaluations will provide further information on the context, costs, and efficiency of the intervention.In this protocol, we describe a pragmatic approach to conducting rigorous research to assess the impacts of a complex water supply intervention on severe diarrhoeal disease and cholera in an unstable, low-resource setting representative of cholera-affected areas. In particular, we discuss a series of pre-identified risks and linked mitigation strategies as well as the value of combining different data collection methods and preparation of multiple analysis scenarios to account for possible deviations from the protocol. The study described here has the potential to provide robust evidence to support more effective cholera control in challenging, high-burden settings.This trial is registered on clinicaltrials.gov ( NCT02928341 , 10th October 2016) and has received ethics approval from the London School of Hygiene and Tropical Medicine (8913, 10603) and from the Ethics Committee from the School of Public Health, University of Kinshasa, Democratic Republic of the Congo (ESP/CE/088/2015).RESUME (VERSION FRANçAISE): Please note this translation has been generated by the authors and has not been checked against the original, peer-reviewed English version by the Journal. Any discrepancies between the two versions should be raised with the authors. Cette traduction a été préparée par les auteurs et sa conformité avec la version anglaise revue par les pairs n’a pas été vérifiée par le journal. Toute différence entre les deux versions doit être signalée aux auteurs. INTRODUCTION: Les maladies diarrhéiques restent une cause majeure de mortalité et morbidité dans le monde. Le choléra seul cause environ 95’000 morts par an, dont la plupart dans des contextes endémiques où l’accès à l’eau est inadéquat. Tandis qu’une stratégie globale pour l’élimination du choléra d’ici à 2030 appelle des investissements dans l’amélioration des services d’approvisionnement en eau, il y a peu de données probantes et rigoureuses sur l’impact d’un approvisionnement en eau amélioré sur la transmission endémique du choléra dans les contextes urbains à faibles ressources. Notre protocole d’étude est conçu pour livrer une évaluation d’impact épidémiologique pragmatique d’une intervention d’approvisionnement en eau à large échelle à Uvira, République Démocratique du Congo, un point focal de transmission du choléra. MéTHODES/CONCEPTION: Un essai randomisé par grappes par échelons (stepped-wedge cluster randomised trial, SW-CRT) a été conçu pour évaluer l’impact d’une intervention d’approvisionnement en eau potable à large échelle sur l’incidence du choléra parmi les 280'000 habitants d’Uvira. La ville a été divisée en 16 grappes, dans lesquelles de nouvelles bornes fontaines et branchements individuels seront installés suivant une séquence randomisée sur une période allant jusqu’à 8 semaines par grappe. Le principal résultat de l’essai sera l’incidence mensuelle des cas de choléra « confirmés » (patients positifs par tests de détection rapide) et des cas « suspects » (patients admis au centre de traitement du choléra). Des évaluations de processus et économique menées en parallèle fourniront des informations complémentaires sur le contexte, les coûts et l’efficience de l’intervention. DISCUSSION: Dans ce protocole, nous présentons une approche pragmatique pour effectuer une recherche rigoureuse visant à évaluer les impacts d’une intervention complexe d’approvisionnement en eau sur la diarrhée sévère et le choléra dans un contexte instable et à faibles ressources, représentatif des zones affectées par le choléra. En particulier, nous considérons une série de risques pré-identifiés et les stratégies de mitigation associées ainsi que la valeur de combiner différentes méthodes de collecte de données et de préparer de multiples scénarios d’analyse pour tenir compte d’éventuelles déviations du protocole. L’étude présentée ici a le potentiel de fournir des évidences scientifiques robustes pour soutenir des stratégies de contrôle du choléra plus efficientes dans les contextes difficiles qui sont fortement affectés. ENREGISTREMENT DE L’ESSAI: Cet essai est enregistré sur clinicaltrials.gov ( NCT02928341 , 10 octobre 2016) et a reçu les approbations éthiques de la London School of Hygiene and Tropical Medicine (8913, 10603) ainsi que de l’Ecole de Santé Publique de l’Université de Kinshasa, République Démocratique du Congo (ESP/CE/088/2015).

Background COVID-19 outcomes and risk factors, including comorbidities and medication regimens, in people living with diabetes (PLWD) are poorly defined for low- and middle-income countries. Methods The Provincial Health Data Centre (Western Cape, South Africa) is a health information exchange collating patient-level routine health data for approximately 4 million public sector health care seekers. Data from COVID-19 patients diagnosed between March and July 2020, including PLWD, were analysed to describe risk factors, including dispensed diabetes medications and comorbidities, and their association with COVID-19 outcomes in this population. Findings There were 64,476 COVID-19 patients diagnosed. Of 9305 PLWD, 44.9% were hospitalised, 4.0% admitted to ICU, 0.6% received ventilation and 15.4% died. In contrast, proportions of COVID-19 patients without diabetes were: 12.2% hospitalised, 1.0% admitted, 0.1% ventilated and 4.6% died. PLWD were significantly more likely to be admitted (OR:3.73, 95 %CI: 3.53, 3.94) and to die (OR:3.01, 95 %CI: 2.76,3.28). Significant hospitalised risk factors included HIV infection, chronic kidney disease, current TB, male sex and increasing age. Significant risk factors for mortality were CKD, male sex, HIV infection, previous TB and increasing age. Pre-infection use of insulin was associated with a significant increased risk for hospitalisation (OR:1·39, 95 %CI:1·24,1·57) and mortality (OR1·49, 95 %CI:1·27; 1·74) and metformin was associated with a reduced risk for hospitalisation (OR:0·62,95 %CI:0·55, 0·71) and mortality (OR 0·77, 95 %CI:0·64; 0·92). Interpretation Using routine health data from this large virtual cohort, we have described the association of infectious and noncommunicable comorbidities as well as pre-infection diabetes medications with COVID-19 outcomes in PLWD in the Western Cape, South Africa. Funding This research was funded in part, by the Wellcome Trust 203135/Z/16/Z, through support of NT. For the purpose of open access, the author has applied a CC BY public copyright licence to any Author Accepted Manuscript version arising from this submission. The Wellcome Centre for Infectious Diseases Research in Africa is supported by core funding from the Wellcome Trust [203135/Z/16/Z]. NT receives funding from the CIDRI-Africa Wellcome Trust grant (203135/Z/16/Z), and NT and TT receive funding from the NIH H3ABioNET award (U24HG006941). NT receives funding from the UKRI/MRC (MC_PC_MR/T037733/1).

Background In patients with tuberculous pericarditis [TBP] adjunctive prednisolone reduces the incidence of constrictive pericarditis. It is unknown whether prednisolone permeates adequately into pericardial fluid. Drug measurements in pericardial fluid require invasive procedures, and thus less invasive methods are needed to perform full pharmacokinetic characterization of prednisolone in large numbers of patients. We sought to evaluate the relationship between prednisolone concentrations in pericardial fluid, plasma, and saliva. Methods Plasma, pericardial fluid, and saliva samples were collected at 7 time points from TBP patients randomized to 120 mg prednisolone or placebo. Compartmental pharmacokinetic parameters, peak concentration [Cmax], and 0–24 h area under the concentration-time curve [AUC0–24] were identified in plasma, saliva and pericardial fluid. Results There were five patients each in the prednisolone and placebo groups. Prednisolone concentrations were best described using a one compartment model. The absorption half-life into plasma was 1 h, while that into pericardial fluid was 9.4 h, which led to a median time-to-maximum concentration in plasma of 2.0 h versus 5.0 h in pericardial fluid [p = 0.048]. The concentration-time profiles in pericardial fluid versus plasma exhibited system hysteresis. The pericardial fluid-to-plasma Cmax peak concentration ratio was 0.28 (p = 0.032), while the AUC0–24 ratio was 0.793. The concentration-time profiles in saliva had a similar shape to those in plasma, but the saliva-to-plasma Cmax was 0.59 [p = 0.032]. Conclusion The prednisolone AUC0–24 achieved in pericardial fluid approximates that in plasma, but the Cmax is low due to delayed absorption. Saliva can be used as surrogate sampling site for pericardial fluid prednisolone.

Microalgae-based bulk production, especially for biofuel, is not yet economically feasible. One way to improve financial performance of such systems is to maximise value through a biorefinery approach (e.g. co-production streams, waste minimisation). This can be implemented via extraction of valuable intracellular compounds upon cell disruption; however both low-cost, energy efficient, and scalable cell disruption techniques, and green chemicals are required. Waste heat is a readily available resource in most production plants, and can be used to power a hydrothermal pre-treatment (HTP) step to disrupt the cells. In this study, we use HTP (120–180 °C, 5–30 min) to disrupt Chlorella sp. cell walls. We perform a subsequent water-miscible solvent and/or urea extraction (UX) to solubilise and recover proteins. The maximum extraction efficiency of 62% was achieved after HTP at 180 °C for 10 min. Regardless of the reaction time, 120 °C was found to be ineffective for protein extraction. The efficiency can be further increased to 84% if a filter-washing step with acetone and urea is implemented. Most of the recovered proteins are between 8 to 14 kDa across all temperature ranges, suggesting that extraction efficiency depended both on partial protein hydrolysis and on accessibility to solvent (i.e. cell wall degradation, solid dispersion, membrane solubilisation). The most significant amino acid losses on a per mole basis were lysine (22%) and arginine (14%). The production of flexible and high-value protein-based products via HTP-UX may enable a circular and sustainable production step for microalgal biorefineries, while improving the downstream fuel processes through nitrogen heteroatom reduction.

This paper presents results of research that has developed a set of diagnostic and decision-support tools for assessing sanitation services city-wide. It highlights features of the tools and illustrates key results from their validation through application in five cities worldwide. Collective use of these tools reveals and explains the complexities of the enabling environment and political economy within which sanitation services are delivered. Results present not only the status quo of services but also reasons for them being so. The tools have proven effective in guiding the collection, analysis and discussion of evidence, as a precursor to detailed feasibility studies, necessary to ultimately plan appropriate city-wide sanitation interventions.

ObjectivesCortisol plays a key role in initiating and maintaining different sleep stages. Patients with Addison’s disease (AD) frequently report disrupted sleep, and their hydrocortisone medication regimes do not restore the natural diurnal rhythm of cortisol. However, few studies have investigated relations between sleep quality, especially as measured by polysomnographic equipment, and night-time cortisol concentrations in patients with AD.MethodsWe used sleep-adapted EEG to monitor a full night of sleep in seven patients with AD and seven healthy controls. We sampled salivary cortisol before bedtime, at midnight, upon awakening and at 30 min post waking.ResultsControls had lower cortisol concentrations than patients before bedtime and at midnight. During the second half of the night, patient cortisol concentrations declined steeply, while control concentrations increased steadily. Whereas most controls experienced a positive cortisol awakening response, all patients experienced a decrease in cortisol concentrations from waking to 30 min post waking (P = 0.003). Patients experienced significantly lower proportions of slow-wave sleep (SWS;P = 0.001), which was associated with elevated night-time cortisol concentrations.ConclusionOverall, these results suggest that patients with AD demonstrate different patterns of night-time cortisol concentrations to healthy controls and that relatively elevated concentrations are associated with a reduction of SWS. These hormonal and sleep architectural aberrations may disrupt the routine sleep-dependent processes of memory consolidation, and hence, may explain, at least partially, the memory impairments often experienced by patients with AD.

Sleep is a critical biological process, essential for cognitive well-being. Neuroscientific literature suggests there are mechanistic relations between sleep disruption and memory deficits, and that varying concentrations of cortisol may play an important role in mediating those relations. Patients with Addison’s disease (AD) experience consistent and predictable periods of sub- and supra-physiological cortisol concentrations due to lifelong glucocorticoid replacement therapy, and they frequently report disrupted sleep and impaired memory. These disruptions and impairments may be related to the failure of replacement regimens to restore a normal circadian rhythm of cortisol secretion. Available data provides support for existing theoretical frameworks which postulate that in AD and other neuroendocrine, neurological, or psychiatric disorders, disrupted sleep is an important biological mechanism that underlies, at least partially, the memory impairments that patients frequently report experiencing. Given the literature linking sleep disruption and cognitive impairment in AD, future initiatives should aim to improve patients’ cognitive performance (and, indeed, their overall quality of life) by prioritizing and optimizing sleep. This review summarizes the literature on sleep and cognition in AD, and the role that cortisol concentrations play in the relationship between the two.

Background Primary adrenal insufficiency (Addison's disease) is a rare medical condition usually associated with hyperkalemia or normokalemia. We report a rare case of Addison's disease, coexisting with hypokalemia, requiring treatment. Case presentation In this case, a 42-year-old man was admitted to the intensive care unit with a history of loss of consciousness and severe hypoglycemia. His blood tests showed metabolic acidosis, low concentrations of cortisol 6 nmol/L (normal 68–327 nmol/L), and high plasma adrenocorticotropic hormone 253 pmol/L (normal 1.6–13.9 pmol/L), and he was diagnosed with primary adrenal insufficiency. Surprisingly, his serum potassium was low, 2.3 mmol/L (normal 3.5–5.1 mmol/L), requiring replacement over the course of his admission. Computed tomography scan of the adrenal glands showed features suggestive of unilateral adrenal tuberculosis. Investigations confirmed renal tubulopathy. The patient responded favorably to cortisol replacement, but never required fludrocortisone. Conclusions Coexistence of hypokalemia with Addison’s disease is unusual. We recommend investigation of the cause of hypokalemia in its own right, if it occurs with primary adrenal insufficiency.

Objective We wished to determine the prevalence, etiology, presentation, and available management strategies for primary adrenal insufficiency (PAI) in South Africa (SA), hypothesizing a prevalence greater than the described 3.1 per million. There is great inequity in healthcare allocation, as two parallel healthcare systems exist, potentially modifying PAI patients’ clinical profiles, private being better resourced than public healthcare. Methods An online survey of physicians’ experience relating to PAI. Results The physicians were managing 811 patients, equal to a prevalence of 14.2 per million. Likely causes of PAI in public/ academic vs private settings included: AIDS-related [304 (44.8%) vs 5 (3.8%); pppp = 0.500], genetic including adrenoleukodystrophy (ALD) [5 (0.7%) vs 16 (12.0%); pp = 0.008 and 126 (15.5%) in adrenal crisis. Features suggestive of a crisis were hypoglycaemia [40 (78.4%) vs 42 (48.8%); p = 0.001], shock [36 (67.9%) vs 31(36.9%); pp = 0.031]. Greater unavailability of antibody testing in the public vs. the private sector [32 (66.7%) vs 30 (32.1%); p = 0.001], [serum-ACTH 25 (52.1%) vs 16 (19.5%); pp = 0.015]. Many patients, 389(66.7%) were not using identification, indicating that they need steroids in an emergency. Conclusion A survey of South African physicians suggests a higher prevalence than previously reported. Patients presented with typical symptoms, and 15.5% presented in adrenal crisis. Significant disparities in the availability of physicians’ expertise, diagnostic resources, and management options were noted in the public versus private settings. Greater awareness among health practitioners to timeously diagnose PAI is required to prevent a life-threatening outcome.

We estimated the costs and benefits of a community-led total sanitation (CLTS) intervention using the empirical results from a cluster-randomized controlled trial in rural Ethiopia. We modelled benefits and costs of the intervention over 10 years, as compared to an existing local government program. Health benefits were estimated as the value of averted mortality due to diarrheal disease and the cost of illness arising from averted diarrheal morbidity. We also estimated the value of time savings from avoided open defecation and use of neighbours&rsquo, latrines. Intervention delivery costs were estimated top-down based on financial records, while recurrent costs were estimated bottom-up from trial data. We explored methodological and parameter uncertainty using one-way and probabilistic sensitivity analyses. Avoided mortality accounted for 58% of total benefits, followed by time savings from increased access to household latrines. The base case benefit&ndash, cost ratio was 3.7 (95% CI: 1.9&ndash, 5.4) and the net present value was Int&rsquo, l $1,193,786 (95% CI: 406,017&ndash, 1,977,960). The sources of the largest uncertainty in one-way sensitivity analyses were the effect of the CLTS intervention and the assumed lifespan of an improved latrine. Our results suggest that CLTS interventions can yield favourable economic returns, particularly if follow-up after the triggering is implemented intensively and uptake of improved latrines is achieved (as opposed to unimproved).

We evaluated the performance of a commercial multiplex tandem polymerase chain reaction (PCR) for detection of dermatophytes and other fungi in skin and nail specimens by (1) testing a range of fungal and bacterial reference cultures, (2) retrospectively testing a set of skin and nail specimens with known microscopy and culture results, and (3) prospectively testing skin and nail specimens in parallel to microscopy and culture. The AusDiagnostics Dermatophytes and Other Fungi assay accurately detected and identified a range of common dermatophytes to species, species complex or genus level, as well as Candida, Aspergillus and Scopulariopsis spp. It was unable to detect uncommon dermatophytes such as Nannizzia fulva (previously Microsporum fulvum), and Paraphyton cookei (previously Microsporum cookei). PCR identified a dermatophyte in 25.9% of prospective specimens which were culture negative. Sensitivity, specificity, positive predictive value, and negative predictive value were highest where microscopy and PCR results were combined, versus microscopy and culture combined, which highlights the significant contribution of microscopy in the diagnostic pathway. This assay has the potential to reduce the workload and results turnaround time associated with culturing and identification of dermatophytes, although microscopy remains important.

Oxygenic photosynthetic organisms use solar energy to split water into protons, electrons, and oxygen. Unicellular green algae like Chlamydomonas reinhardtii have evolved the additional ability to reduce protons to produce hydrogen (H2) via chloroplast hydrogenases (HYDA1 and HYDA2) under light-driven anaerobic conditions. In wild type cells, H2 production is limited by proton and electron supply to HYDA; most electrons are diverted to ferredoxin-NADP+-reductase. To enhance electron supply to HYDA and improve H2 production, variant ferredoxins with reduced ferredoxin-NADP+-reductase affinity have been demonstrated in vitro. Ferredoxin-hydrogenase fusions have also been tested, but achieving robust expression in vivo has been challenging. To improve efficiency, we here combine (1) a ferredoxin-HYDA fusion containing (2) a mutant FDX1 ferredoxin (D19A, D58A) with lowered affinity for ferredoxin-NADP+-reductase, utilising (3) a strongly inducible lhcbm9 promoter for controllable expression, and (4) a transgene construct containing introns for higher nuclear expression levels. Fusion constructs with 15 (pDK6-15) or 25 (pDK6-25) amino acid linkers were expressed in the nucleus of a HYDA1/HYDA2 knockout strain. Under illuminated, sulfur-deprived conditions, the variant ferredoxin-HYDA fusion strains yielded 3.0 and 4.6-fold more H2 than the wild type background strain over a 6-day period (typical purity range attained; 92–97%), confirming that the variant ferredoxin fused to HYDA is functional in vivo, strongly inducible, expresses at a similar level to the native HYDA gene, and significantly increases light-driven H2 production over wild type levels, likely by reducing losses to other electron acceptors such as ferredoxin-NADP+-reductase.

Context: Patients with Addison's disease (AD) have increased cardiovascular mortality. Objective: To study visceral fat and conventional and exploratory cardiovascular risk factors in patients with AD. Subjects: Patients (n = 76; n = 51 women) with AD and 76 healthy control subjects were matched for sex, age, body mass index (BMI), and smoking habits. Main outcome measures: The primary outcome variable was visceral abdominal adipose tissue (VAT) measured using computed tomography. Secondary outcome variables were prevalence of metabolic syndrome (MetS) and 92 biomarkers of cardiovascular disease. Results: The mean 6 standard deviation age of all subjects was 53 6 14 years; mean BMI, 25 6 4 kg/ m2; and mean duration of AD, 17 6 12 years. The median (range) daily hydrocortisone dose was 30 mg (10 to 50 mg). Median (interquartile range) 24-hour urinary free cortisol excretion was increased in patients vs controls [359 nmol (193 to 601 nmol) vs 175 nmol (140 to 244 nmol); P, 0.001]. VAT did not differ between groups. After correction for multiple testing, 17 of the 92 studied biomarkers differed significantly between patients and control subjects. Inflammatory, proinflammatory, and proatherogenic risk biomarkers were increased in patients [fold change (FC),.1] and vasodilatory protective marker was decreased (FC, < 1). Twenty-six patients (34%) vs 12 control subjects (16%) fulfilled the criteria for MetS (P = 0.01). Conclusion: Despite higher cortisol exposure, VAT was not increased in patients with AD. The prevalence of MetS was increased and several biomarkers of cardiovascular disease were adversely affected in patients with AD.

Access to continuous water supply is key for improving health and economic outcomes in rural areas of low- and middle-income countries, but the factors associated with continuous water access in these areas have not been well characterized. We surveyed 4786 households for evidence of technical, financial, institutional, social, and environmental predictors of rural water service continuity (WSC), defined as the percentage of the year that water is available from a source. Multiply imputed fractional logistic regression models that account for the survey design were used to assess operational risks to WSC for piped supply, tube wells, boreholes, springs, dug wells, and surface water for the rural populations of Bangladesh, Pakistan, Ethiopia, and Mozambique. Multivariable regressions indicated that households using multiple water sources were associated with lower WSC in Bangladesh, Pakistan, and Mozambique. However, the possibility must be considered that households may use more than one water source because services are intermittent. Water scarcity and drought were largely unassociated with WSC, suggesting that service interruptions may not be primarily due to physical water resource constraints. Consistent findings across countries may have broader relevance for meeting established targets for service availability as well as human health.

Introduction: Post-prandial hypoglycaemia (PPH) after consumption of protein is a vanishingly rare condition. Congenital hyperinsulinism is the most common cause of persistent hypoglycemia in infants and children, although it is uncommon to be diagnosed in adulthood. Dominant activation of glutamate dehydrogenase, encoded for by the GLUD1 gene, causes the hyperinsulinemia/hyperammonemia syndrome (HHS). Within a family known to be affected by HHS, the first presentation in adulthood, is intriguing. Clinical case: A 32-year old male presented with new-onset generalised non-convulsive seizures and family history of genetically proven HHS in his mother, two siblings and two of their offspring. A heterozygous missense mutation (R269H) in exon 7 of the GLUD1 gene was identified several years ago in this family. Our patient was screened clinically for hypoglycemia in childhood, but he never underwent genetic testing, as he was not considered affected. Affected family members developed confusion and hypoglycaemia following high-protein meals, which was reversed with glucose and limiting protein intake, lessened further attacks. Our patient’s school performance was poor and described feeling unwell after eating large protein meals. He was fully orientated, but his mini-mental state examination was impaired at 21/30. He was hyper-reflexic with spreading of ankle and crossed adductor reflexes. Considering his family history, we performed continuous glucose monitoring for 14 days, revealing several post-prandial and fasting hypoglycaemic episodes (as low as 1.8 mmol/L) and an HbA1c of 3.5%. HHS was proven (serum ammonia 70 µmol/L; normal less than 35 µmol/L) and genetic analysis revealed an identical mutation to the aforementioned. Diazoxide was titrated to abrogate hypoglycaemia. Genetic screening of the remaining family members will be undertaken. Clinical lessons: Among causes of PPH, HHS is rare. Missed diagnoses can have profound neurological and cognitive consequences. The intrafamilial variability is demonstrable however; it is likely that HHS was missed in our patient’s initial presentation in childhood, as seizures and intellectual disability in adulthood are exceptionally rare complications of this condition. It demonstrates that it is critical to perform genetic testing on all members of an affected family, even in those asymptomatic. Genetic diagnoses of PPH are rarely made in adulthood, as there is often a low diagnostic suspicion at such a late presentation. References:1. K. E. Snider, S. Becker, L. Boyajian et al; Genotype and Phenotype Correlations in 417 Children With Congenital Hyperinsulinism; J Clin Endocrinol Metab, February 2013, 98(2):E355-E3632. Charles A. Stanley; Hyperinsulinism/hyperammonemia syndrome: insights into the regulatory role of glutamate dehydrogenase in ammonia metabolism; Molecular Genetics and Metabolism81 (2004) S45-S51 Unless otherwise noted, all abstracts presented at ENDO are embargoed until the date and time of presentation. For oral presentations, the abstracts are embargoed until the session begins. Abstracts presented at a news conference are embargoed until the date and time of the news conference. The Endocrine Society reserves the right to lift the embargo on specific abstracts that are selected for promotion prior to or during ENDO.

Sonolysis has been proposed as a promising treatment technology to remove per- and polyfluoroalkyl substances (PFASs) from contaminated water. The mechanism of degradation is generally accepted to be high temperature pyrolysis at the bubble surface with dependency upon surface reaction site availability. However, the parametric effects of the ultrasonic system on PFAS degradation are poorly understood, making upscale challenging and leading to less than optimal use of ultrasonic energy. Hence, a thorough understanding of these parametric effects could lead to improved efficiency and commercial viability. Here, reactor characterisation was performed at 44, 400, 500 and 1000 kHz using potassium iodide (KI) dosimetry, sonochemiluminescence (SCL), and sonoluminescence (SL) in water and PFOS solution. Then the degradation of PFOS (10 mg / L in 200 mL solution) was investigated at these four frequencies. At 44 kHz, no PFOS degradation was observed. At 400, 500 and 1000 kHz the amount of degradation was 96.9, 93.8 and 91.2%, respectively, over four hours and was accompanied by stoichiometric fluoride release, indicating mineralisation of the PFOS molecule. Close correlation of PFOS degradation trends with KI dosimetry and SCL intensity was observed, which suggested degradation occurred under similar conditions to these sonochemical processes. At 1000 kHz, where the overall intensity of collapse was significantly reduced (measured by SL), PFOS degradation was not similarly decreased. Discussion is presented that suggests a solvated electron degradation mechanism for PFOS may occur in ultrasonic conditions.

Preventing infectious disease has often been the primary rationale for public investment in sanitation. However, broader aspects of sanitation such as privacy and safety are important to users across settings, and have been linked to mental wellbeing. The aim of this study is to investigate what people most value about sanitation in low-income areas of Maputo, Mozambique, to inform a definition and conceptual model of sanitation-related quality of life. Our approach to qualitative research was rooted in economics and applied the capability approach, bringing a focus on what people had reason to value. We undertook 19 in-depth interviews and 8 focus group discussions. After eliciting attributes of “a good life” in general, we used them to structure discussion of what was valuable about sanitation. We applied framework analysis to identify core attributes of sanitation-related quality of life, and used pile-sorting and triad exercises to triangulate findings on attributes’ relative importance. The five core attributes identified were health, disgust, shame, safety, and privacy. We present a conceptual model illustrating how sanitation interventions might improve quality of life via changes in these attributes, and how changes are likely to be moderated by conversion factors (e.g. individual and environmental characteristics). The five capability-based attributes are consistent with those identified in studies of sanitation-related insecurity, stress and motives in both rural and urban areas, which is supportive of theoretical generalisability. Since two people might experience the same toilet or level of sanitation service differently, quality of life effects of interventions may be heterogeneous. Future evaluations of sanitation interventions should consider how changes in quality of life might be captured., Highlights • Different sanitation interventions might improve quality of life to varying degrees. • We explored attributes of sanitation-related quality of life as capabilities. • We identified five core attributes: health, disgust, shame, safety, and privacy. • Results aligned with studies framed in terms of insecurity, stress and motives. • Conversion factors moderate how sanitation (e.g. a toilet) supports capabilities.

BACKGROUND: Hydrogen is a clean, versatile fuel and energy carrier which can be produced by a range of renewable technologies for combustion, use in fuel cells, or as a manufacturing feedstock. Despite its attraction and significant technological innovation, commercial feasibility of photobiological hydrogen processes is far from demonstrated.OBJECTIVE: This review examines direct photobiological biohydrogen systems, with a particular focus on the main obstacles that must be overcome to deliver commercially viable, net energy positive systems. As part of this process the interactions between future photobiological biohydrogen systems and other parts of a renewable energy economy are examined to analyse potential technology integration paths.RESULTS: The primary driver for renewably produced hydrogen is the potential for CO2 emissions reductions. Renewable hydrogen is largely solar driven, either directly (e.g. natural photosynthesis, or bio-inspired devices) or indirectly (e.g. fermentation, electrical hydrolysis). A significant market for hydrogen already exists and is supported by extensive infrastructure providing significant opportunities for emerging renewable hydrogen streams. Several key physiological obstacles to efficient photobiohydrogen production have already been overcome, with oxygen tolerance as the most significant remaining problem.CONCLUSIONS: A much deeper understanding of photosynthetic biology is required before existing knowledge can be integrated with real world systems. Cross-fertilisation between engineering and biology represents the best path forward for implementation as a robust biotechnology.

Efficient photosynthetic biomass production in a high rate pond (HRP) or a photobioreactor (PBR) represents the first step of microalgae platforms for the production of renewable fuels, animal feeds and a diverse range of high value products. This study analyses the interplay between solar energy input, ambient temperature and system surface area to volume (SA:V) ratio in terms of photosynthetic performance (yield, areal and volumetric productivity, photon conversion efficiency). Ten pilot scale trials were conducted under subtropical conditions using 2 microalgae strains (Chlorella sorokiniana and Chlorella sp.) in 5 different cultivation system geometries: HRPs, flat panel PBRs (0.75 m and 1.5 m high) and tubular PBRs (0.74 m and 1.49 m high). The evaluation of culture temperature and biomass productivity response to solar irradiance in the five production systems suggests that the optimal SA:V ratio range lies between 43–73 m2 m− 3 for C. sorokiniana in non-cooled systems regardless of system geometry under the conditions tested. The overall photosynthetic performance at higher SA:V ratios was improved for Chlorella sp. using temperature regulation. The highest observed daily photon conversion efficiency (PCE) was 4.44% (based on illuminated PBR surface area and total solar spectrum) in the high flat panel PBR using C. sorokiniana (40.8 g m− 2 d− 1, 0.23 g L− 1 d− 1). The highest achieved mean PCE (based on illuminated PBR surface area and total solar spectrum) was 2.5% in the low tubular PBR with Chlorella sp. (24.9 g m− 2 d− 1, 0.43 g L− 1 d− 1). The trial data provides important design principles to help fast track systems optimisation for near optimal sub-tropical conditions.

Microalgae offer a promising route to the production of high-value products, foods, animal feeds, and biofuels. Efficient algal dewatering strategies are therefore important for minimising energy and costs. Bio-flocculation is a potentially low-cost, low-energy harvesting strategy which can be facilitated by the microbial production of extracellular polymeric substances (EPS), but must be inducible since productive algal culture generally requires cells to be in suspension. Here we show that algal bio-flocculation can be controllably induced using the protozoan Tetrahymena. As little as 1:400 starved Tetrahymena to algal cells can be used to initiate rapid bio-flocculation. We demonstrate that stimulators of ryanodine receptors (caffeine and p-chlorocresol) trigger exocytosis in Tetrahymena and that inexpensive physicochemical stimuli (ammonium ions, shifts in pH and salinity) can also be effective. We suggest that triggered EPS secretion by protozoans in the starved state may explain apparently spontaneous bioflocculation of algae in both natural and artificial systems.

Summary The global population is predicted to increase from ~7.3 billion to over 9 billion people by 2050. Together with rising economic growth, this is forecast to result in a 50% increase in fuel demand, which will have to be met while reducing carbon dioxide (CO 2) emissions by 50–80% to maintain social, political, energy and climate security. This tension between rising fuel demand and the requirement for rapid global decarbonization highlights the need to fast‐track the coordinated development and deployment of efficient cost‐effective renewable technologies for the production of CO 2 neutral energy. Currently, only 20% of global energy is provided as electricity, while 80% is provided as fuel. Hydrogen (H2) is the most advanced CO 2‐free fuel and provides a ‘common’ energy currency as it can be produced via a range of renewable technologies, including photovoltaic (PV), wind, wave and biological systems such as microalgae, to power the next generation of H2 fuel cells. Microalgae production systems for carbon‐based fuel (oil and ethanol) are now at the demonstration scale. This review focuses on evaluating the potential of microalgal technologies for the commercial production of solar‐driven H2 from water. It summarizes key global technology drivers, the potential and theoretical limits of microalgal H2 production systems, emerging strategies to engineer next‐generation systems and how these fit into an evolving H2 economy.

Outdoor microalgae systems are a promising platform for fuels and chemicals, but are currently limited by relatively low productivities. This study investigated the effects of photoacclimation on the productivity of Chlamydomonas reinhardtii grown under fluctuating light regimes which simulate well-mixed cultures in outdoor reactors. Simulations represented cells cycling between high light and dark zones in high-density ( HD Fluc , light fraction (LF) = 0.5) and low-density ( LD Fluc , LF = 0.9) cultures. Each fluctuating treatment was controlled by cultures grown under non-fluctuating light of the same hourly average irradiance ( HD Avg and LD Avg ) to differentiate between light dosage and regime. The large dark fraction of HD Fluc resulted in a low-light acclimated phenotype displaying up-regulation of light harvesting pigments and low NPQ caused by reduced levels of the dissipative protein LHCSR3. All other treatments led to high-light acclimation phenotypes. HD Fluc showed an estimated three-fold lower biomass yield relative to light absorbed and significant reductions in the quantum yield of PSII compared to HD Avg . This suggests that during high light periods of fluctuating cycles, higher absorption and an inability to safely dissipate excess light, resulted in greater photodamage and respiration required for repair. A framework for including these findings in predictive modelling of mass cultures is presented.

Many rural point-water sources in developing countries consist of wells or boreholes equipped with handpumps. Various estimates have been made of the functionality of such water points, and functionality is now routinely monitored in national and local surveys of service performance. We argue, however, that a single binary (functional/non-functional) indicator is crude and insufficient to provide much information about service sustainability. We set out a categorization of functionality which includes three sub-categories of functional water points and five non-functional sub-categories, with well/handpump water points in mind. We use a simple model to demonstrate that reduction of high rates of early post-construction abandonment and reduction of total downtimes would greatly improve service performance. We show that functionality levels for multi-age populations of wells or boreholes equipped with handpumps would not normally be expected to exceed about 85 per cent. We recommend going beyond functionality monitoring via the collection of quantitative data on rates of abandonment, frequency and duration of breakdown, combined with descriptive narratives of actions to manage and repair water points, in order to generate more nuanced understanding of service performance.