Priority setting for adult malnutrition and nutritional screening in healthcare: a James Lind Alliance.

BACKGROUND: Malnutrition is one the greatest global health challenges of our generation, leading to the increased utilisation of healthcare resources, as well as morbidity and mortality. Research has primarily been driven by industry, academia and clinical working groups and has had little involvement from patients and carers. The project described in the present study aimed to establish a priority setting partnership allowing patients, carers and healthcare professionals an opportunity to influence the research agenda. METHODS: A national survey was conducted to gather malnutrition uncertainties and identify key issues (i.e. areas within scope where an evidence-base is lacking) from those with experience of malnutrition. Uncertainties were analysed according to themes. Similar questions were grouped and summary questions were developed. A second survey was conducted and respondents were asked to choose their 10 most important summary questions. A workshop was conducted to finalise the top 10 research priorities from the most frequently indicated uncertainties on the interim survey. RESULTS: Overall, 1128 uncertainty questions were submitted from 268 people. The interim survey had 71 responses and a list of the top 26 questions was generated for the workshop. There were 26 questions discussed, ranked and agreed by healthcare professionals, carers and patients at the workshop. The top 10 research priorities were then chosen. These included questions on oral nutritional supplements, vulnerable groups, screening, community care, use of body mass index and technology. CONCLUSIONS: The top 10 research priorities in malnutrition and nutritional screening have been identified from a robust process involving patients, carers and healthcare professionals.

Collapse of superconductivity in cuprates via ultrafast quenching of phase coherence.

The possibility of driving phase transitions in low-density condensates through the loss of phase coherence alone has far-reaching implications for the study of quantum phases of matter. This has inspired the development of tools to control and explore the collective properties of condensate phases via phase fluctuations. Electrically gated oxide interfaces1,2, ultracold Fermi atoms3,4 and cuprate superconductors5,6, which are characterized by an intrinsically small phase stiffness, are paradigmatic examples where these tools are having a dramatic impact. Here we use light pulses shorter than the internal thermalization time to drive and probe the phase fragility of the Bi2Sr2CaCu2O8+δ cuprate superconductor, completely melting the superconducting condensate without affecting the pairing strength. The resulting ultrafast dynamics of phase fluctuations and charge excitations are captured and disentangled by time-resolved photoemission spectroscopy. This work demonstrates the dominant role of phase coherence in the superconductor-to-normal state phase transition and offers a benchmark for non-equilibrium spectroscopic investigations of the cuprate phase diagram.

Practical measurement of body composition using bioelectrical impedance, air displacement plethysmography and ultrasound in stable outpatients with short bowel syndrome receiving home parenteral nutrition: comparison of agreement between the methods.

BACKGROUND: People diagnosed with intestinal failure (IF) as a result of short bowel syndrome are dependent on home parenteral nutrition (HPN). Measuring nutritional status is essential for monitoring treatment. The present study aimed to determine the agreement and feasibility of three methods bioelectrical impedance analysis (BIA), ultrasound and air displacement plethysmography (ADP) for measuring body composition in people receiving HPN. METHODS: Body composition data were collected from patients attending an IF clinic. RESULTS: There were 50 participants recruited and data were collected for BIA (n = 46), ultrasound (n = 49) and ADP (n = 9). Numbers for ADP were much lower because of a lack of participant uptake. Fat-free mass (FFM) measured by BIA and ultrasound in comparison to ADP was found to have good intraclass correlation (ICC) 0.791 (95% confidence interval (CI) CI  -0.21 to 0.96) and a moderate ICC 0.659 [95% (CI) -0.27 to 0.92], respectively. Fat mass (FM) measured by both BIA and ultrasound in comparison to ADP was found to have moderate ICC 0.660 (95% CI -0.28 to 0.92) and poor ICC -0.005 (95% CI -0.73 to 0.65), respectively. CONCLUSIONS: Compared to ADP, BIA indicated moderate to good agreement for measuring body composition, whereas ultrasound indicated far less agreement, particularly when measuring FM. The lack of uptake of ADP suggests that participants found the Bodpod (COSMED Srl, Shepperton, UK) unfavourable. Considering that ultrasound has limited agreement and ADP was not the preferred option for participants, BIA shows some potential. However, the difference between ADP and BIA was larger for FM compared to FFM, which needs to be considered in the clinical setting.

Regional Spatial-Temporal Spread of Citrus Huanglongbing Is Affected by Rain in Florida.

Citrus huanglongbing (HLB), associated with 'Candidatus Liberibacter asiaticus' (Las), disseminated by Asian citrus psyllid (ACP), has devastated citrus in Florida since 2005. Data on HLB occurrence were stored in databases (2005 to 2012). Cumulative HLB-positive citrus blocks were subjected to kernel density analysis and kriging. Relative disease incidence per county was calculated by dividing HLB numbers by relative tree numbers and maximum incidence. Spatiotemporal HLB distributions were correlated with weather. Relative HLB incidence correlated positively with rainfall. The focus expansion rate was 1626 m month-1, similar to that in Brazil. Relative HLB incidence in counties with primarily large groves increased at a lower rate (0.24 year-1) than in counties with smaller groves in hotspot areas (0.67 year-1), confirming reports that large-scale HLB management may slow epidemic progress.

The use of turbulent flow chromatography for rapid, on-line analysis of tryptic digests.

RATIONALE: Following digestion of proteins with trypsin, digests are typically subjected to further 'clean-up' prior to liquid chromatography/mass spectometry (LC/MS) analysis, in order to reduce the complexity of the digested matrix, as well as helping to remove residual denaturants and reduction/alkylation reagents prior to injection onto the analytical HPLC column. Often, this is carried out using off-line techniques, and is not ideally suited to high-throughput workloads, for example in clinical laboratories. METHODS: Bovine serum albumin (BSA) was used as a model protein. Following denaturation with urea, reduction/alkylation, and digestion with trypsin, the analytical recovery of a selection of proteotypic BSA peptides was assessed using a two-dimensional, turbulent flow chromatography method. Peptides were identified using a Q Exactive™ mass spectometer operating in full-scan mode. RESULTS: Total analysis time (including the on-line sample clean-up) was 15 min per injection. Aside from the most hydrophilic peptide selected, ATEEQLK, recovery using the turbulent flow chromatography systems was greater than 30% for all remaining peptides (N = 17), and exceeded 50% for 12 of the 18 peptides studied. There was a broad correlation between the hydrophobicity factor and the observed recovery. CONCLUSIONS: This study suggests that turbulent flow chromatography offers a rapid, on-line alternative to solid-phase extraction for the analysis of peptide digests by LC/MS. A wide range of column chemistries are available, and the technique can be further optimised for analyses which are targetted to specific peptides. As with turbulent flow chromatography for small-molecule workflows, this approach may be ideally suited to high-throughput applications, such as those which are emerging from within clinical laboratories.

A versatile laser-based apparatus for time-resolved ARPES with micro-scale spatial resolution.

We present the development of a versatile apparatus for 6.2 eV laser-based time and angle-resolved photoemission spectroscopy with micrometer spatial resolution (time-resolved µ-ARPES). With a combination of tunable spatial resolution down to ∼11 µm, high energy resolution (∼11 meV), near-transform-limited temporal resolution (∼280 fs), and tunable 1.55 eV pump fluence up to 3 mJ/cm2, this time-resolved µ-ARPES system enables the measurement of ultrafast electron dynamics in exfoliated and inhomogeneous materials. We demonstrate the performance of our system by correlating the spectral broadening of the topological surface state of Bi2Se3 with the spatial dimension of the probe pulse, as well as resolving the spatial inhomogeneity contribution to the observed spectral broadening. Finally, after in situ exfoliation, we performed time-resolved µ-ARPES on a ∼30 µm flake of transition metal dichalcogenide WTe2, thus demonstrating the ability to access ultrafast electron dynamics with momentum resolution on micro-exfoliated materials.

Detection of subpopulations of leucocytes in different subgroups of semen sample qualities.

The role of leucocytospermia in male subfertility is a much debated topic despite being a frequent finding. This study aimed to identify the role of leucocytes, leucocyte subpopulations and natural killer cells in male subfertility. Seventy-sex subfertile men attending a regional andrology unit were recruited into this prospective study and subdivided into groups based on their semen analysis. The different leucocyte subpopulations were identified using immunocytochemical staining. Significant levels of CD3 helper T lymphocytes (P < 0.001) were present in the oligospermic, asthenospermic, oligoasthenospermic and obstructive azoospermic group compared to the normospermic group. Significant levels of B cells (P < 0.05) were present in the asthenospermic, oligoasthenospermic and obstructive azoospermic group. The natural killer cells (CD56) were significantly raised in the oligoasthenospermic and obstructive azoospermic group (P < 0.05). Our study suggests that leucocytospermia impairs sperm function through enhanced T helper cell modulation, increased B cell population which leads to increased levels of antisperm antibody and natural killer cells mediated sperm damage. The site of seminal leucocyte production is not necessarily confined to the vas or the epididymis.

General practice in the Armed Forces: a definition and model.

Armed Forces General Practice is in an unprecedented time of challenge with the demands of contiguous worldwide operations in austere environments, reorganisation of defence, budgetary constraints and manpower shortfalls. We propose a model of this crucial area of military medical care as a key academic and practical reference point, which will help retain, and perhaps even enable, the development of this clinical speciality over the next decade. It provides a formalised definition and a basis for education, training and research in Military General Practice; it also has the advantage of highlighting the all-encompassing nature of military primary care when compared to the nearest equivalent model--that of civilian General Practice.

Optical manipulation of Rashba-split 2-dimensional electron gas.

In spintronics, the two main approaches to actively control the electrons' spin involve static magnetic or electric fields. An alternative avenue relies on the use of optical fields to generate spin currents, which can bolster spin-device performance, allowing for faster and more efficient logic. To date, research has mainly focused on the optical injection of spin currents through the photogalvanic effect, and little is known about the direct optical control of the intrinsic spin-splitting. To explore the optical manipulation of a material's spin properties, we consider the Rashba effect. Using time- and angle-resolved photoemission spectroscopy (TR-ARPES), we demonstrate that an optical excitation can tune the Rashba-induced spin splitting of a two-dimensional electron gas at the surface of Bi2Se3. We establish that light-induced photovoltage and charge carrier redistribution - which in concert modulate the Rashba spin-orbit coupling strength on a sub-picosecond timescale - can offer an unprecedented platform for achieving optically-driven spin logic devices.

Enhancing the activity and stability of carbon-supported platinum-gadolinium nanoalloys towards the oxygen reduction reaction.

The activity/stability towards the ORR of Pt x Gd/C nanoalloys has been enhanced by controlling the atmosphere during the dealloying process. By minimising the formation of porous nanoarchitectures, the ORR activity is increased, and is accompanied by higher activity retention and attenuation of metal dissolution on cycling to high voltage.

Manchester Arena bombing: lessons learnt from a mass casualty incident.

On 22 May 2017 Salman Abedi detonated an improvised explosive device in the Manchester Arena resulting in 23 deaths (including the attacker). This was the deadliest terrorist attack on UK soil since the 2005 London bombings, but was only one of five mass casualty terrorist attacks in the UK in 2017. Preparation for mass casualty incidents (MCI) is obligatory, involving such methods as multiagency tabletop exercises, mock hospital exercises, as well as simulation and training for clinicians in managing the injuries that would be anticipated in such an event. Even in the best prepared units, such an incident will pose significant challenges due to the unpredictable nature of these events with respect to timing and number of casualties. Following an MCI, local and national reviews are undertaken to assess the effectiveness of the response, but also to identify areas where lessons can be learnt and to disseminate these to allow inclusion in future planning. We present the experience following a mass casualty terrorist incident along with a number of lessons learnt from this event.

Radiotherapy-Induced Senescence and its Effects on Responses to Treatment.

Radiotherapy is still a treatment of choice for many malignancies, often in combination with other strategies. However, its efficacy is limited by the dose that can be safely administered without eliciting serious side-effects, as well as the fact that recurrence is common, particularly in large tumours. Combining radiotherapy with drugs that could sensitise cells to radiation and/or reduce the factors that promote the recovery of the surviving cancer cells is a promising approach. Ionising radiation has been shown to induce senescence and the accumulation of senescent cells creates a microenvironment that facilitates neoplastic growth. This provides a rationale to test the addition of anti-senescent drugs, some of which are already available in the clinic, to radiotherapy protocols. Here, we discuss the relevance of radiotherapy-induced senescent cell accumulation and the potential interventions to minimise its negative effects.

Cavity-enhanced high harmonic generation for extreme ultraviolet time- and angle-resolved photoemission spectroscopy.

With its direct correspondence to electronic structure, angle-resolved photoemission spectroscopy (ARPES) is a ubiquitous tool for the study of solids. When extended to the temporal domain, time-resolved (TR)-ARPES offers the potential to move beyond equilibrium properties, exploring both the unoccupied electronic structure as well as its dynamical response under ultrafast perturbation. Historically, ultrafast extreme ultraviolet sources employing high-order harmonic generation (HHG) have required compromises that make it challenging to achieve a high energy resolution-which is highly desirable for many TR-ARPES studies-while producing high photon energies and a high photon flux. We address this challenge by performing HHG inside a femtosecond enhancement cavity, realizing a practical source for TR-ARPES that achieves a flux of over 1011 photons/s delivered to the sample, operates over a range of 8-40 eV with a repetition rate of 60 MHz. This source enables TR-ARPES studies with a temporal and energy resolution of 190 fs and 22 meV, respectively. To characterize the system, we perform ARPES measurements of polycrystalline Au and MoTe2, as well as TR-ARPES studies on graphite.

Direct determination of mode-projected electron-phonon coupling in the time domain.

Ultrafast spectroscopies have become an important tool for elucidating the microscopic description and dynamical properties of quantum materials. In particular, by tracking the dynamics of nonthermal electrons, a material's dominant scattering processes can be revealed. Here, we present a method for extracting the electron-phonon coupling strength in the time domain, using time- and angle-resolved photoemission spectroscopy (TR-ARPES). This method is demonstrated in graphite, where we investigate the dynamics of photoinjected electrons at the [Formula: see text] point, detecting quantized energy-loss processes that correspond to the emission of strongly coupled optical phonons. We show that the observed characteristic time scale for spectral weight transfer mediated by phonon-scattering processes allows for the direct quantitative extraction of electron-phonon matrix elements for specific modes.

Effects of parathyroid hormone on plasma and urinary adenosine 3',5'-monophosphate in man.

The effects of parathyroid hormone (PTH) on plasma and urinary adenosine 3',5'-monophosphate (cyclic AMP) levels were studied in normal subjects. Under basal conditions normal adults have plasma concentrations of cyclic AMP ranging from 10 to 25 nmoles/liter and excrete from 1.5 to 5 mumoles of cyclic AMP per g of urinary creatinine. About one-half to two-thirds of the cyclic AMP excreted in the urine is derived from the plasma by glomerular filtration, and the remainder is produced by the kidney. Renal production of cyclic AMP is partly under the control of PTH. It can be suppressed by infusions of calcium and stimulated by infusions of the calcium chelating agent, EDTA. Infusions of PTH in doses up to 10 mU/kg per min were associated with dose-related increases both in urinary cyclic AMP and phosphate. Infusions of PTH in doses ranging from 20 to 80 mU/kg per min did not lead to any further increase in phosphaturia but did lead to further marked increases in urinary cyclic AMP. A modest increase in plasma cyclic AMP was noted when PTH was infused at 40 mU/kg per min. Anephric patients failed to show appreciable increases in plasma cyclic AMP in response to large doses of PTH but did show expected increases in response to glucagon. Surgical removal of parathyroid adenomas from nine patients with primary hyperparathyroidism was invariably followed by a decrease in urinary cyclic AMP, PTH, in large doses, and calcium infusion produced up to 2-fold increases in the other known naturally occurring cyclic nucleotide, guanosine 3',5'-monophosphate (cyclic GMP).

Characterization of metabolites of the chemopreventive agent curcumin in human and rat hepatocytes and in the rat in vivo, and evaluation of their ability to inhibit phorbol ester-induced prostaglandin E2 production.

Curcumin, the yellow pigment in turmeric, has been shown to prevent malignancies in a variety of tissues in rodents, especially in the intestinal tract. Pharmacological activities of curcumin in cells in situ germane to chemoprevention, such as inhibition of expression of cyclooxygenase-2 (COX-2), require drug concentrations in the 10(-5) - 10(-4) M range. The systemic bioavailability of curcumin is low, so that its pharmacological activity may be mediated, in part, by curcumin metabolites. To investigate this possibility, we compared curcumin metabolism in human and rat hepatocytes in suspension with that in rats in vivo. Analysis by high-performance liquid chromatography with detection at 420 and 280 nm permitted characterization of metabolites with both intact diferoylmethane structure and increased saturation of the heptatrienone chain. Chromatographic inferences were corroborated by mass spectrometry. The major metabolites in suspensions of human or rat hepatocytes were identified as hexahydrocurcumin and hexahydrocurcuminol. In rats, in vivo, curcumin administered i.v. (40 mg/kg) disappeared from the plasma within 1 h of dosing. After p.o. administration (500 mg/kg), parent drug was present in plasma at levels near the detection limit. The major products of curcumin biotransformation identified in rat plasma were curcumin glucuronide and curcumin sulfate whereas hexahydrocurcumin, hexahydrocurcuminol, and hexahydrocurcumin glucuronide were present in small amounts. To test the hypothesis that curcumin metabolites resemble their progenitor in that they can inhibit COX-2 expression, curcumin and four of its metabolites at a concentration of 20 microM were compared in terms of their ability to inhibit phorbol ester-induced prostaglandin E2 (PGE2) production in human colonic epithelial cells. Curcumin reduced PGE2 levels to preinduction levels, whereas tetrahydrocurcumin, previously shown to be a murine metabolite of curcumin, hexahydrocurcumin, and curcumin sulfate, had only weak PGE2 inhibitory activity, and hexahydrocurcuminol was inactive. The results suggest that (a) the major products of curcumin biotransformation by hepatocytes occur only at low abundance in rat plasma after curcumin administration; and (b) metabolism of curcumin by reduction or conjugation generates species with reduced ability to inhibit COX-2 expression. Because the gastrointestinal tract seems to be exposed more prominently to unmetabolized curcumin than any other tissue, the results support the clinical evaluation of curcumin as a colorectal cancer chemopreventive agent.

The effects of chemical or surgical deafferentation on [3H]-acetylcholine release from rat spinal cord.

Cholinergic modulation of nociceptive transmission through both nicotinic and muscarinic receptors in the spinal cord represents an important mechanism in pain signaling. However, what neuronal elements release acetylcholine and how release might change in response to deafferentation are unclear. The present studies demonstrated Ca++- and K+-dependent release of [3H]-acetylcholine from slices of regional areas of rat spinal cord. That [3H]-acetylcholine was synthesized from [3H]-choline was demonstrated by the lack of [3H]-acetylcholine release following incubation with either the choline uptake inhibitor hemicholinium or the choline acetyltransferase inhibitor bromoacetylcholine. Rats treated neonatally with capsaicin or with spinal nerve ligation as adults showed a significantly decreased K+-stimulated release of [3H]-acetylcholine from dorsal horn but not ventral horn lumbar spinal cord slices. In rats subjected to dorsal rhizotomy, while basal release from lumbar dorsal spinal cord slices was reduced, K+-stimulated [3H]-acetylcholine release, while decreased, was not significantly different compared with controls. The data presented here show that there are regional differences in the release of acetylcholine from spinal cord and that this release can be modulated by chemical or surgical deafferentation. These results also indicate that the source of acetylcholine in the dorsal cord originates mainly from resident somata and their collaterals, interneurons and/or descending terminals, with only very minor contributions coming from primary afferents. The present data help to further elucidate the role of acetylcholine in spinal signaling, particularly with respect to the effects of nerve injury and nociceptive neurotransmission.