Dissolved organic matter quantity and quality response of tropical rainforest headwater rivers to the transition from dry to wet season.

Dissolved organic matter (DOM) and its composition in aquatic ecosystems is a key indicator of ecosystem function and an important component of the global carbon cycle. Tropical rainforest headwaters play an important role in global carbon cycling. However, there is a large uncertainty on how DOM sources interact during mobilisation and the potential fate of associated carbon and nutrients. Using field techniques to measure dissolved organic carbon (DOC) concentration and composition, changes in DOM source from headwaters to larger downstream rivers were observed. This study shows that the hydrological connectivity, developed during the transition from dry to wet seasons, changes the DOM supply and transport across a tropical river catchment. The observed variability in the DOC-river discharge relationship provides further evidence of the changes in the DOM supply in a small headwater. This novel insight into the seasonal changes of the dynamics of DOM supply to the river helps understanding the mobilization of terrestrial DOM to tropical headwaters and its export from smaller to larger rivers. It also highlights the data gap in the study of smaller headwaters which may account for uncertainty in estimating the terrestrial carbon transported by inland waters.

The effect of a 'Sip til Send' policy on patient satisfaction: a quality improvement project.

Patients often are nil by mouth for prolonged periods pre-operatively, which is associated with adverse effects including discomfort, anxiety, thirst and nausea. As a result, several hospitals have introduced a more liberal regimen of pre-operative drinking, with patients encouraged to sip small volumes of water until transfer to the operating theatre ('Sip til Send'). The impact of 'Sip til Send' on patient satisfaction is still to be determined. We hypothesised that the introduction of a 'Sip til Send' policy would increase patient's satisfaction with their pre-operative fluid management regimen. We conducted a staged implementation of a 'Sip til Send' quality improvement initiative in two campuses of a large tertiary teaching hospital. This involved a targeted education and implementation programme that was refined and delivered through 'plan, do, study and act' cycles. Patient satisfaction with their pre-operative fluid management was measured by rating the statement "I am happy with the management of pre-operative drinking", against a five-point Likert scale (0, strongly disagree; 1, disagree; 2, neutral; 3, agree; and 4, strongly agree). Patient satisfaction with pre-operative fluid management was high at baseline, with pooled data for both campuses showing a median (IQR [range]) satisfaction score of 4 (3-4 [1-4]). After the implementation of 'Sip til Send', this improved to a median (IQR [range]) satisfaction score of 4 (4-4 [2-4]) (p < 0.001). The introduction of a 'Sip til Send' policy resulted in an increase in patient satisfaction. Key factors in successful implementation included the provision of a clear explanation of the underlying rationale to patients, nursing and anaesthetic staff, and establishing the policy as the default position for all elective patients.

Phonon Hall Viscosity of Ionic Crystals.

When time-reversal symmetry is broken, the low-energy description of acoustic lattice dynamics allows for a dissipationless component of the viscosity tensor, the phonon Hall viscosity, which captures how phonon chirality grows with the wave vector. In this work, we show that, in ionic crystals, a phonon Hall viscosity contribution is produced by the Lorentz forces on moving ions. We calculate typical values of the Lorentz force contribution to the Hall viscosity using a simple square lattice toy model, and we compare it with literature estimates of the strengths of other Hall-viscosity mechanisms.

A phase IIb, open-label, randomized controlled dose ranging multi-centre trial to evaluate the safety, tolerability, pharmacokinetics and exposure-response relationship of different doses of delpazolid in combination with bedaquiline delamanid moxifloxacin in adult subjects with newly diagnosed, uncomplicated, smear-positive, drug-sensitive pulmonary tuberculosis.

BACKGROUND: Linezolid is an effective, but toxic anti-tuberculosis drug that is currently recommended for the treatment of drug-resistant tuberculosis. Improved oxazolidinones should have a better safety profile, while preserving efficacy. Delpazolid is a novel oxazolidinone developed by LegoChem Biosciences Inc. that has been evaluated up to phase 2a clinical trials. Since oxazolidinone toxicity can occur late in treatment, LegoChem Biosciences Inc. and the PanACEA Consortium designed DECODE to be an innovative dose-ranging study with long-term follow-up for determining the exposure-response and exposure-toxicity relationship of delpazolid to support dose selection for later studies. Delpazolid is administered in combination with bedaquiline, delamanid and moxifloxacin. METHODS: Seventy-five participants with drug-sensitive, pulmonary tuberculosis will receive bedaquiline, delamanid and moxifloxacin, and will be randomized to delpazolid dosages of 0 mg, 400 mg, 800 mg, 1200 mg once daily, or 800 mg twice daily, for 16 weeks. The primary efficacy endpoint will be the rate of decline of bacterial load on treatment, measured by MGIT liquid culture time to detection from weekly sputum cultures. The primary safety endpoint will be the proportion of oxazolidinone class toxicities; neuropathy, myelosuppression, or tyramine pressor response. Participants who convert to negative liquid media culture by week 8 will stop treatment after the end of their 16-week course and will be observed for relapse until week 52. Participants who do not convert to negative culture will receive continuation phase treatment with rifampicin and isoniazid to complete a six-month treatment course. DISCUSSION: DECODE is an innovative dose-finding trial, designed to support exposure-response modelling for safe and effective dose selection. The trial design allows assessment of occurrence of late toxicities as observed with linezolid, which is necessary in clinical evaluation of novel oxazolidinones. The primary efficacy endpoint is the change in bacterial load, an endpoint conventionally used in shorter dose-finding trials. Long-term follow-up after shortened treatment is possible through a safety rule excluding slow-and non-responders from potentially poorly performing dosages. TRIAL REGISTRATION: DECODE was registered in ClinicalTrials.gov before recruitment start on 22 October 2021 (NCT04550832).

Laparoscopic large hiatus hernia repair with mesh reinforcement versus suture cruroplasty alone: a systematic review and meta-analysis.

BACKGROUND: To compare the difference in outcomes in laparoscopic large hiatus hernia (LHH) repair using suture-based and mesh-based repair techniques. METHODS: A systematic search of articles was conducted in PubMed, Medline and Embase using the PRISMA guidelines. Studies comparing recurrences and reoperations in those patients with large hiatal hernia repair (> 30% stomach in the chest, > 5 cm hiatal defect, hiatal surface area > 10 cm2) who had mesh vs no mesh were assessed quantitatively. The impact of mesh on significant intraoperative/postoperative surgical complications was qualitatively assessed. RESULTS: Pooled data included six randomized controlled trials and thirteen observational studies with 1670 patients (824 with no mesh, 846 with mesh). There was a significant reduction in the total recurrence rate with mesh (OR 0.44, 95% CI 0.25-0.80, p = 0.007). Mesh use did not cause significant reduction in recurrences > 2 cm (OR 0.94, 95% CI 0.52-1.67, p = 0.83) or in reoperation rates (OR 0.64, 95% CI 0.39-1.07, p = 0.09). None of the specific meshes assessed were found to be superior in the reduction of recurrence or reoperation rates. Cases of mesh erosion with eventual foregut resection were noted and were associated with synthetic meshes only. CONCLUSION: Mesh reinforcement seemed protective against total recurrence in LHH although this has to be interpreted with caution given the level of heterogeneity introduced by the inclusion of observational studies in the analysis. There was no significant reduction in large recurrences (> 2 cm) or reoperation rate. If the synthetic mesh is to be used patients need to be informed of the risk of mesh erosion.

Pulmonary inflammation promoted by type-2 dendritic cells is a feature of human and murine schistosomiasis.

Schistosomiasis is a parasitic disease affecting over 200 million people in multiple organs, including the lungs. Despite this, there is little understanding of pulmonary immune responses during schistosomiasis. Here, we show type-2 dominated lung immune responses in both patent (egg producing) and pre-patent (larval lung migration) murine Schistosoma mansoni (S. mansoni) infection. Human pre-patent S. mansoni infection pulmonary (sputum) samples revealed a mixed type-1/type-2 inflammatory cytokine profile, whilst a case-control study showed no significant pulmonary cytokine changes in endemic patent infection. However, schistosomiasis induced expansion of pulmonary type-2 conventional dendritic cells (cDC2s) in human and murine hosts, at both infection stages. Further, cDC2s were required for type-2 pulmonary inflammation in murine pre-patent or patent infection. These data elevate our fundamental understanding of pulmonary immune responses during schistosomiasis, which may be important for future vaccine design, as well as for understanding links between schistosomiasis and other lung diseases.

Contribution of physical factors to handpump borehole functionality in Africa.

Handpumps are the main water supply for rural communities across sub-Saharan Africa. However, studies show that >25 % of handpumps are non-functional at any time. We present results from a systematic field study of handpump borehole functionality. The study was designed to investigate the contribution of physical factors to functionality outcomes, including; hydrogeology, borehole configuration, and handpump components. To achieve this, we deconstructed and examined 145 handpump boreholes in Ethiopia, Uganda and Malawi. Pumping tests showed that 19 % of boreholes were located in aquifers with transmissivity below the minimum required to sustain a handpump. Water levels, measured during the dry season, had a complex relationship with borehole configuration and transmissivity. The handpump cylinder was <10 m below the water table at 38 % of sites, which increases the risk of the handpump running dry during intensive use and/or in areas of low transmissivity. The water column was <20 m at 23 % of sites and screens were <10 m long at 29 % of sites and often sub-optimally positioned in the borehole. Borehole depth had no clear relationship with functionality. Using multinomial regression and four functionality categories (functional; unreliable; low yield; unreliable and low yield) as dependant variables, we found that transmissivity is a significant risk factor for the classification of handpump boreholes as low yield. The configuration of the borehole (e.g. cylinder position, screen/casing configuration and water column) is a statistically significant risk factor for the classification of handpump boreholes as unreliable. Handpump components were in poor overall condition but rising main pipes were a particular problem with 53 % of galvanised pipes corroded and 82 % of uPVC pipes damaged, with implications for handpump performance. Our study highlights the importance of; understanding aquifer properties, investing in borehole siting, construction (including supervision) and commissioning, and improving the quality of components and maintenance of handpumps.

Left ventricular dysfunction and intra-ventricular dyssynchrony in idiopathic pulmonary arterial hypertension.

BACKGROUND: Left ventricular (LV) filling pressures are normal in idiopathic pulmonary arterial hypertension (IPAH). However, direct and indirect interactions between the RV and LV can affect LV performance. We explored LV strain and LV intra-ventricular dyssynchrony in IPAH using feature tracking CMR (CMR-FT). METHODS: Seventy IPAH patients and 40 healthy volunteers were included. Patients underwent CMR and right heart catheterisation. The 4-chamber cine was used to calculate LV longitudinal strain (EllLV). LV circumferential (EccLV) and radial strain (ErrLV) were derived from a short axis cine. LV longitudinal, circumferential and radial intra-ventricular dyssynchrony indices were calculated. RESULTS: There were no differences between the IPAH and healthy volunteer group in LV ejection fraction (66.1% vs 64.2% p = 0.6672). EccLV (-29.1 vs -32.1 p = 0.0323) and EllLV (-16.6 vs -23.7 p < 0.0001) were lower in IPAH. In patients with more severe disease, there was greater impairment of ErrLV compared to mild disease (50.9 vs 87.5 P < 0.0001). LV synchrony was impaired in all directions in IPAH. ErrLV was associated with RV ejection fraction (r = 0.66), RV end-systolic volume index (r = -0.59), pulmonary vascular resistance (PVR)(r = 0.51) and stroke volume index (SVI)(r = 0.44). In a multivariate model with age, SVI and PVR, ErrLV (HR 0.970 p = 002) and radial dyssynchrony (HR 3.759 p < 0.0001) independently predicted survival. CONCLUSION: In IPAH, LV is dyssynchronous with impaired function. Measures of LV strain and intraventricular synchrony were associated with known markers of disease severity. These LV variables which are likely to be related to ventricular interaction, may add incremental value to known prognostic variables in IPAH.

Weak-Field Hall Resistivity and Spin-Valley Flavor Symmetry Breaking in Magic-Angle Twisted Bilayer Graphene.

Near a magic twist angle, the lowest energy conduction and valence bands of bilayer graphene moiré superlattices become extremely narrow. The band dispersion that remains is sensitive to the moiré's strain pattern, nonlocal tunneling between layers, and filling-factor-dependent Hartree and exchange band renormalizations. In this Letter, we analyze the influence of these band-structure details on the pattern of flavor symmetry breaking observed in this narrow band system and on the associated pattern of Fermi surface reconstructions revealed by weak-field Hall and Shubnikov-de Haas magnetotransport measurements.

Exact Diagonalization for Magic-Angle Twisted Bilayer Graphene.

We report on finite-size exact-diagonalization calculations in a Hilbert space defined by the continuum-model flat moiré bands of magic angle twisted bilayer graphene. For moiré band filling 3>|ν|>2, where superconductivity is strongest, we obtain evidence that the ground state is a spin ferromagnet. Near |ν|=3, we find Chern insulator ground states that have spontaneous spin, valley, and sublattice polarization, and demonstrate that the anisotropy energy in this order-parameter space is strongly band-filling-factor dependent. We emphasize that inclusion of the remote band self-energy is necessary for a reliable description of magic angle twisted bilayer graphene flat band correlations.

Development of innovative simulation teaching for advanced general practice clinical pharmacists.

BACKGROUND: Advanced General Practice Clinical Pharmacists (GPCPs) are expected to manage patients by undertaking clinical assessment then make safe, competent autonomous decisions. Simulation provides a safe learning environment to develop clinical skills, but is rarely used for postgraduate pharmacist development. AIM: Design and deliver innovative simulation teaching to support Advanced GPCPs in Scotland. SETTING: General Practice. DEVELOPMENT: Experienced clinical pharmacy educators designed a simulation day with ten scenarios based on general practice clinical presentations. Learning objectives were mapped to the National Advanced GPCP competency framework. IMPLEMENTATION: Simulation took place at the National Skills Education Hub, Louisa Jordan National Hospital, Glasgow, November 2020. Participants were briefed prior to each immersive simulation. Mannequins were used if clinical signs were expected to be identified on examination. Verbal and written feedback was given after each simulation. EVALUATION: Pre and post simulation questionnaires were developed. Increase in confidence and competence were reported in all areas pertaining to application of consultation and clinical skills. Qualitative comments from the participants regarding the training course were also favourable with respondents highlighting the value of the training, especially in terms of developing confidence via the real-time feedback. CONCLUSION: This innovative simulation evaluated as being of value to GPCPs in developing clinical confidence and competence when dealing with a variety of typical General Practice scenarios. Plans are underway to establish a Scottish Pharmacy Simulation Faculty which could support this training in each health board.

The effect of organic carbon content on soil compression characteristics.

We investigated the effect of soil organic carbon (SOC) on the consolidation behaviour of soil from two long term field experiments at Rothamsted; the Broadbalk Wheat Experiment and Hoosfield Spring Barley. These experiments are located on soil with similar particle size distributions, and include treatments with SOC contents ranging from approximately 1-3.5 g/100 g. Soils taken from plots with contrasting SOC contents were compressed and deformed in a triaxial cell and the normal consolidation and critical state lines were determined. We found that the compression index was independent of SOC, but the void ratio at any given effective stress was highly correlated with organic carbon content. By comparison with uniaxial compression data, the apparent influence of SOC on the compression index is likely to be due to its effect on soil hydraulic properties rather than any intrinsic effects of strength. The plastic limit test appears to be a useful and simple test to allow direct comparison of soil physical behaviour and expected soil density.

Development and internal validation of clinical prediction models for outcomes of complicated intra-abdominal infection.

BACKGROUND: Complicated intra-abdominal infections (cIAIs) are associated with significant morbidity and mortality. The aim of this study was to describe the clinical characteristics of patients with cIAI in a multicentre study and to develop clinical prediction models (CPMs) to help identify patients at risk of mortality or relapse. METHODS: A multicentre observational study was conducted from August 2016 to February 2017 in the UK. Adult patients diagnosed with cIAI were included. Multivariable logistic regression was performed to develop CPMs for mortality and cIAI relapse. The c-statistic was used to test model discrimination. Model calibration was tested using calibration slopes and calibration in the large (CITL). The CPMs were then presented as point scoring systems and validated further. RESULTS: Overall, 417 patients from 31 surgical centres were included in the analysis. At 90 days after diagnosis, 17.3 per cent had a cIAI relapse and the mortality rate was 11.3 per cent. Predictors in the mortality model were age, cIAI aetiology, presence of a perforated viscus and source control procedure. Predictors of cIAI relapse included the presence of collections, outcome of initial management, and duration of antibiotic treatment. The c-statistic adjusted for model optimism was 0.79 (95 per cent c.i. 0.75 to 0.87) and 0.74 (0.73 to 0.85) for mortality and cIAI relapse CPMs. Adjusted calibration slopes were 0.88 (95 per cent c.i. 0.76 to 0.90) for the mortality model and 0.91 (0.88 to 0.94) for the relapse model; CITL was -0.19 (95 per cent c.i. -0.39 to -0.12) and - 0.01 (- 0.17 to -0.03) respectively. CONCLUSION: Relapse of infection and death after complicated intra-abdominal infections are common. Clinical prediction models were developed to identify patients at increased risk of relapse or death after treatment, these now require external validation.

Defining tetrahydrobiopterin responsiveness in phenylketonuria: Survey results from 38 countries.

BACKGROUND: A subset of patients with phenylketonuria benefit from treatment with tetrahydrobiopterin (BH4), although there is no consensus on the definition of BH4 responsiveness. The aim of this study therefore was to gain insight into the definitions of long-term BH4 responsiveness being used around the world. METHODS: We performed a web-based survey targeting healthcare professionals involved in the treatment of PKU patients. Data were analysed according to geographical region (Europe, USA/Canada, other). RESULTS: We analysed 166 responses. Long-term BH4 responsiveness was commonly defined using natural protein tolerance (95.6%), improvement of metabolic control (73.5%) and increase in quality of life (48.2%). When a specific value for a reduction in phenylalanine concentrations was reported (n = 89), 30% and 20% were most frequently used as cut-off values (76% and 19% of respondents, respectively). When a specific relative increase in natural protein tolerance was used to define long-term BH4 responsiveness (n = 71), respondents most commonly reported cut-off values of 30% and 100% (28% of respondents in both cases). Respondents from USA/Canada (n = 50) generally used less strict cut-off values compared to Europe (n = 96). Furthermore, respondents working within the same center answered differently. CONCLUSION: The results of this study suggest a very heterogeneous situation on the topic of defining long-term BH4 responsiveness, not only at a worldwide level but also within centers. Developing a strong evidence- and consensus-based definition would improve the quality of BH4 treatment.

Patient's thoughts and expectations about centres of expertise for PKU.

BACKGROUND: In the Netherlands (NL) the government assigned 2 hospitals as centres of expertise (CE) for Phenylketonuria (PKU), while in the United Kingdom (UK) and Germany no centres are assigned specifically as PKU CE's. METHODS: To identify expectations of patients/caregivers with PKU of CEs, a web-based survey was distributed through the national Phenylketonuria societies of Germany, NL and UK. RESULTS: In total, 105 responded (43 patients, 56 parents, 4 grandparents, 2 other) of whom 59 were from NL, 33 from UK and 13 from Germany. All participants (n = 105) agreed that patients and/or practitioners would benefit from CEs. The frequency patients would want to visit a CE, when not treated in a CE (n = 83) varied: every hospital visit (24%, n = 20), annual or bi-annual (45%, n = 37), at defined patient ages (6%, n = 5), one visit only (22%, n = 18), or never (4%, n = 3). Distance was reported as a major barrier (42%, n = 35). 78% (n = 65) expected CE physicians and dieticians to have a higher level of knowledge than in non-CE centres. For participants already treated in a CE (n = 68), 66% requested a more extensive annual or bi-annual review. In general, psychology review and neuropsychologist assessment were identified as necessary by approximately half of the 105 participants. In addition, 66% (n = 68) expected a strong collaboration with patient associations. CONCLUSION: In this small study, most participants expected that assigning CEs will change the structure of and delivery of Phenylketonuria care.

WKB Estimate of Bilayer Graphene's Magic Twist Angles.

Graphene bilayers exhibit zero-energy flatbands at a discrete series of magic twist angles. In the absence of intrasublattice interlayer hopping, zero-energy states satisfy a Dirac equation with a non-Abelian SU(2) gauge potential that cannot be diagonalized globally. We develop a semiclassical WKB approximation scheme for this Dirac equation by introducing a dimensionless Planck's constant proportional to the twist angle, solving the linearized Dirac equation around AB and BA turning points, and connecting Airy function solutions via bulk WKB wave functions. We find zero-energy solutions at a discrete set of values of the dimensionless Planck's constant, which we obtain analytically. Our analytic flatband twist angles correspond closely to those determined numerically in previous work.

Complications and functional outcomes after ileo-anal pouch excision-a systematic review of 14 retrospective observational studies.

PURPOSE: The ileo-anal pouch (IAP) has been the gold standard procedure for maintenance of bowel continuity after panproctocolectomy for ulcerative colitis, familial adenomatous polyposis or hereditary non-polyposis colorectal cancer. However, the IAP has an estimated failure rate of 13% at 10 years post-procedure (Tulchinsky et al., Ann Surg 238(2):229-34, 2003), which can result in pouch excision (P.E.). This systematic review aims to synthesise all the available studies reporting post-operative outcomes of P.E. and its impact on patient quality of life (QoL), when available, which have not previously been summarised. METHODS: PubMed, Embase, Medline and the Cochrane library databases were searched with terms 'Pouch AND excision' OR 'Pouch AND removal' OR 'Pouch AND remove' OR 'IAP AND excision'. All studies reporting post-operative morbidity, mortality or functional outcomes in patients who had P.E. were included. Studies with < 5 patients, non-English studies and conference abstracts were excluded. RESULTS: 14 studies comprising 1601 patients were included. Overall complications varied from 18 to 63% with the most common being persistent perineal sinus (9-40%) or surgical site infection (wound-2 to 30%; intra-abdominal collection-3 to 24%). The mortality rate was between 0.58 and 1.4%. QoL is generally lower in P.E. patients compared to the normal population across various QoL measures and P.E. patients often had urinary and sexual dysfunction post-operatively. CONCLUSIONS: There is a substantial incidence of complications after P.E.; however, there is no evidence describing QoL pre- and post-P.E. Further longitudinal research comparing QoL in patients undergoing P.E. and other treatment options such as indefinite diversion is required to definitively assess QoL post-procedure.

Voltage-Controlled Magnetic Reversal in Orbital Chern Insulators.

Chern insulator ferromagnets are characterized by a quantized anomalous Hall effect and have so far been identified experimentally in magnetically doped topological insulator thin films and in bilayer graphene moiré superlattices. We classify Chern insulator ferromagnets as either spin or orbital, depending on whether the orbital magnetization results from spontaneous spin polarization combined with spin-orbit interactions, as in the magnetically doped topological insulator case, or directly from spontaneous orbital currents, as in the moiré superlattice case. We argue that, in a given magnetic state, characterized, for example, by the sign of the anomalous Hall effect, the magnetization of an orbital Chern insulator will often have opposite signs for weak n and weak p electrostatic or chemical doping. This property enables pure electrical switching of a magnetic state in the presence of a fixed magnetic field.

Electrical switching of magnetic order in an orbital Chern insulator.

Magnetism typically arises from the joint effect of Fermi statistics and repulsive Coulomb interactions, which favours ground states with non-zero electron spin. As a result, controlling spin magnetism with electric fields-a longstanding technological goal in spintronics and multiferroics1,2-can be achieved only indirectly. Here we experimentally demonstrate direct electric-field control of magnetic states in an orbital Chern insulator3-6, a magnetic system in which non-trivial band topology favours long-range order of orbital angular momentum but the spins are thought to remain disordered7-14. We use van der Waals heterostructures consisting of a graphene monolayer rotationally faulted with respect to a Bernal-stacked bilayer to realize narrow and topologically non-trivial valley-projected moiré minibands15-17. At fillings of one and three electrons per moiré unit cell within these bands, we observe quantized anomalous Hall effects18 with transverse resistance approximately equal to h/2e2 (where h is Planck's constant and e is the charge on the electron), which is indicative of spontaneous polarization of the system into a single-valley-projected band with a Chern number equal to two. At a filling of three electrons per moiré unit cell, we find that the sign of the quantum anomalous Hall effect can be reversed via field-effect control of the chemical potential; moreover, this transition is hysteretic, which we use to demonstrate non-volatile electric-field-induced reversal of the magnetic state. A theoretical analysis19 indicates that the effect arises from the topological edge states, which drive a change in sign of the magnetization and thus a reversal in the favoured magnetic state. Voltage control of magnetic states can be used to electrically pattern non-volatile magnetic-domain structures hosting chiral edge states, with applications ranging from reconfigurable microwave circuit elements to ultralow-power magnetic memories.