Altered Mental Status and Cardiac Failure Due to Thiamine Deficiency in an Overweight Teen.

We describe an overweight but otherwise previously healthy 17-year-old female who presented with altered mental status and rapidly progressive weakness. She was ultimately diagnosed with Wernicke encephalopathy and wet beriberi resulting from severe thiamine deficiency. She required admission to the pediatric ICU because of hypoventilation with progressive weakness and worsening encephalopathy and was found to have impaired cardiac function as assessed by echocardiography. Her heart function and encephalopathy improved on initiation of thiamine repletion. She remained in inpatient rehabilitation for 10 months but still remained weak at discharge. Thiamine deficiency is not commonly considered in the United States as a diagnosis other than in patients with severe alcohol use disorder. However, thiamine may be depleted in as little as 2 weeks if nutrition is inadequate. In such a setting, thiamine deficiency is an important etiology to consider early in the pediatric patient with altered mentation especially because it can be readily and safely treated.

Flow similarity, stochastic branching, and quarter-power scaling in plants.

The origin of allometric scaling patterns that are multiples of one-fourth has long fascinated biologists. While not universal, quarter-power scaling relationships are common and have been described in all major clades. Several models have been advanced to explain the origin of such patterns, but questions regarding the discordance between model predictions and empirical data have limited their widespread acceptance. Notable among these is a fractal branching model that predicts power-law scaling of both metabolism and physical dimensions. While a power law is a useful first approximation to some data sets, nonlinear data compilations suggest the possibility of alternative mechanisms. Here, we show that quarter-power scaling can be derived using only the preservation of volume flow rate and velocity as model constraints. Applying our model to land plants, we show that incorporating biomechanical principles and allowing different parts of plant branching networks to be optimized to serve different functions predicts nonlinearity in allometric relationships and helps explain why interspecific scaling exponents covary along a fractal continuum. We also demonstrate that while branching may be a stochastic process, due to the conservation of volume, data may still be consistent with the expectations for a fractal network when one examines sub-trees within a tree. Data from numerous sources at the level of plant shoots, stems, and petioles show strong agreement with our model predictions. This theoretical framework provides an easily testable alternative to current general models of plant metabolic allometry.

Thermal imagery of woodland tree canopies provides new insights into drought-induced tree mortality.

Our understanding of how water dynamics determines the probability of tree mortality during drought is incomplete. Here we help address this shortcoming by coupling approaches from the disciplines of ecophysiology, geophysics and remote sensing in a woodland ecosystem undergoing protracted drying. Water uptake and use strategies varied between the dominant canopy species of the ecosystem. At one extreme were species that tightly regulate their water status, which is broadly consistent with the definition of isohydry. The higher leaf temperatures revealed by thermal imagery of these isohydric species are likely a reflection of reduced latent cooling owing to a stringent control of transpiration rate. Where silty sediments occur in the root zone, this strategy may have the effect of limiting the water sources available to these species during prolonged drought because of an insufficient hydraulic gradient for water uptake. In contrast were species that allowed their water status to fluctuate, operating in a fashion more consistent with anisohydry. For these species, latent cooling owing to relatively high transpiration rates maintained leaf temperatures near, or below, the ambient air temperature. The resulting drawdown in leaf water potential between soil and leaves in these anisohydric species may generate a sufficient hydraulic gradient to enable water uptake from silty soil during seasonal or prolonged droughts. In this way the spatial distribution of fine textured soil could indicate areas where the isohydric hydraulic control strategy is disadvantageous during prolonged droughts or where annual soil water recharge has fallen below a critical threshold.

The Role of Virtual Consultations in Plastic Surgery During COVID-19 Lockdown.

BACKGROUND: COVID-19 has led to government enforced 'lockdown' in the UK severely limiting face-to-face patient interaction. Virtual consultations present a means for continued patient access to health care. Our aim was to evaluate the use of virtual consultations (VCons) during lockdown and their possible role in the future. METHODS: An anonymous survey was disseminated to UK and European plastic surgeons via social media, email sharing and via the European Association of Societies of Aesthetic Plastic Surgery newsletter. Uptake of VCons, modality, effectiveness, safety and future utility were assessed. RESULTS: Forty-three senior plastic surgeons responded to the survey. The majority of the respondents (97.7%) reported using VCons during COVID-19 lockdown, of which 74.4% had no prior experience. Two-thirds of surgeons utilised commercial platforms such as Zoom, FaceTime and Skype, 38.1% of respondents did not know about or were unsure about adequate encryption for health care use, and just under a half (47.6%) reported they were unaware of or lacking GDPR compliance. Most (97.6%) say they are likely to use virtual consultations after lockdown. CONCLUSION: Virtual consultations have had a crucial role in patient care during UK lockdown. It is clear that they will serve as an adjunct to face-to-face consultation in the future. Further regulation is required to ensure platforms offer adequate safety and security measures and are compliant with relevant data protection laws. LEVEL OF EVIDENCE IV: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Evaluating the patient experience of an emergency burns assessment service in a UK burn unit using a service user evaluation questionnaire and process mapping.

An evaluation of the patient experience, from referral to first assessment, at an outpatient emergency burns assessment service in a UK burn unit. All patients attending their first appointment were invited to complete a questionnaire, covering patient expectations following referral, their journey to the hospital and an evaluation of the appointment. Process mapping was used to map the patient journey within the department and identify functional bottlenecks and waits. 35 new patients completed the questionnaire over a four-week period in February 2019. 70% of respondents had received no printed information about their condition or the hospital prior to the appointment and 28% of patients did not know what to expect from attending the clinic. Patients incurred high direct and indirect costs in order to attend their appointments. 86% patients felt more confident about looking after their injury following their appointment. The patient journey through the clinic was observed for 19 patients; four functional bottlenecks were identified. The longest waits were for clinical photography and completion of nursing paperwork. A multimodal approach to this quality improvement project has enabled the service to identify process bottlenecks and through consultation with stakeholders, develop staff training and patient information to improve the service.

Two sides to every leaf: water and CO2 transport in hypostomatous and amphistomatous leaves.

Leaves with stomata on both upper and lower surfaces, termed amphistomatous, are relatively rare compared with hypostomatous leaves with stomata only on the lower surface. Amphistomaty occurs predominantly in fast-growing herbaceous annuals and in slow-growing perennial shrubs and trees. In this paper, we present the current understanding and hypotheses on the costs and benefits of amphistomaty related to water and CO2 transport in contrasting leaf morphologies. First, there is no evidence that amphistomatous species achieve higher stomatal densities on a projected leaf area basis than hypostomatous species, but two-sided gas exchange is less limited by boundary layer effects. Second, amphistomaty may provide a specific advantage in thick leaves by shortening the pathway for CO2 transport between the atmosphere and the chloroplasts. In thin leaves of fast-growing herbaceous annuals, in which both the adaxial and abaxial pathways are already short, amphistomaty enhances leaf-atmosphere gas-exchange capacity. Third, amphistomaty may help to optimise the leaf-interior water status for CO2 transport by reducing temperature gradients and so preventing the condensation of water that could limit CO2 diffusion. Fourth, a potential cost of amphistomaty is the need for additional investments in leaf water transport tissue to balance the water loss through the adaxial surface.

Development and validation of the Burnt Hand Outcome Tool (BHOT): A patient-led questionnaire for adults with hand burns.

Hand burns are unique in their functional, aesthetic and emotional impact on patients. Measuring the progress of a patient's ability to carry out essential and desired tasks, their emotional state, interaction with society as well as scar, pain and itch as their burn heals, has until now relied on the use of a combination of several different tools. We have developed a questionnaire specifically to address the multiple different aspects of the impact of a hand burn on a patient. This has been validated in a study of adult patients with hand burns in a UK unit, by a variety of psychometric tests. Ninety-four patients entered the study and questionnaires were completed over the course of a year at five time points. The total BHOT and DASH questionnaires completed at each time point was as follows: 86 before; 52 healed; 29 at 3 months; 31 at 6 months; 28 at 1 year, i.e. 226 DASH and 226 BHOT questionnaires in total. The questionnaire has been shown to have excellent reliability, criterion validity, construct validity, and responsiveness. The result is the Burnt Hand Outcome Tool (BHOT), a patient reported, quick and easy to use yet comprehensive questionnaire specifically for adult patients with burns to the hand.

Apparent Overinvestment in Leaf Venation Relaxes Leaf Morphological Constraints on Photosynthesis in Arid Habitats.

Leaf veins supply the mesophyll with water that evaporates when stomata are open to allow CO2 uptake for photosynthesis. Theoretical analyses suggest that water is optimally distributed in the mesophyll when the lateral distance between veins (dx) is equal to the distance from these veins to the epidermis (dy), expressed as dx:dy ≈ 1. Although this theory is supported by observations of many derived angiosperms, we hypothesize that plants in arid environments may reduce dx:dy below unity owing to climate-specific functional adaptations of increased leaf thickness and increased vein density. To test our hypothesis, we assembled leaf hydraulic, morphological, and photosynthetic traits of 68 species from the Eucalyptus and Corymbia genera (termed eucalypts) along an aridity gradient in southwestern Australia. We inferred the potential gas-exchange advantage of reducing dx beyond dy using a model that links leaf morphology and hydraulics to photosynthesis. Our observations reveal that eucalypts in arid environments have thick amphistomatous leaves with high vein densities, resulting in dx:dy ratios that range from 1.6 to 0.15 along the aridity gradient. Our model suggests that, as leaves become thicker, the effect of reducing dx beyond dy is to offset the reduction in leaf gas exchange that would result from maintaining dx:dy at unity. This apparent overinvestment in leaf venation may be explained from the selective pressure of aridity, under which traits associated with long leaf life span, high hydraulic and thermal capacitances, and high potential rates of leaf water transport confer a competitive advantage.

Morphological and moisture availability controls of the leaf area-to-sapwood area ratio: analysis of measurements on Australian trees.

The leaf area-to-sapwood area ratio (LA:SA) is a key plant trait that links photosynthesis to transpiration. The pipe model theory states that the sapwood cross-sectional area of a stem or branch at any point should scale isometrically with the area of leaves distal to that point. Optimization theory further suggests that LA:SA should decrease toward drier climates. Although acclimation of LA:SA to climate has been reported within species, much less is known about the scaling of this trait with climate among species. We compiled LA:SA measurements from 184 species of Australian evergreen angiosperm trees. The pipe model was broadly confirmed, based on measurements on branches and trunks of trees from one to 27 years old. Despite considerable scatter in LA:SA among species, quantile regression showed strong (0.2 < R1 < 0.65) positive relationships between two climatic moisture indices and the lowermost (5%) and uppermost (5-15%) quantiles of log LA:SA, suggesting that moisture availability constrains the envelope of minimum and maximum values of LA:SA typical for any given climate. Interspecific differences in plant hydraulic conductivity are probably responsible for the large scatter of values in the mid-quantile range and may be an important determinant of tree morphology.

Isometric partitioning of hydraulic conductance between leaves and stems: balancing safety and efficiency in different growth forms and habitats.

Recent advances in modelling the architecture and function of the plant hydraulic network have led to improvements in predicting and interpreting the consequences of functional trait variation on CO2 uptake and water loss. We build upon one such model to make novel predictions for scaling of the total specific hydraulic conductance of leaves and shoots (kL and kSH , respectively) and variation in the partitioning of hydraulic conductance. Consistent with theory, we observed isometric (slope = 1) scaling between kL and kSH across several independently collected datasets and a lower ratio of kL and kSH , termed the leaf-to-shoot conductance ratio (CLSCR ), in arid environments and in woody species. Isometric scaling of kL and kSH supports the concept that hydraulic design is coordinated across the plant. We propose that CLSCR is an important adaptive trait that represents the trade-off between efficiency and safety at the scale of the whole plant.

Smaller, faster stomata: scaling of stomatal size, rate of response, and stomatal conductance.

Maximum and minimum stomatal conductance, as well as stomatal size and rate of response, are known to vary widely across plant species, but the functional relationship between these static and dynamic stomatal properties is unknown. The objective of this study was to test three hypotheses: (i) operating stomatal conductance under standard conditions (g (op)) correlates with minimum stomatal conductance prior to morning light [g (min(dawn))]; (ii) stomatal size (S) is negatively correlated with g (op) and the maximum rate of stomatal opening in response to light, (dg/dt)(max); and (iii) g (op) correlates negatively with instantaneous water-use efficiency (WUE) despite positive correlations with maximum rate of carboxylation (Vc (max)) and light-saturated rate of electron transport (J (max)). Using five closely related species of the genus Banksia, the above variables were measured, and it was found that all three hypotheses were supported by the results. Overall, this indicates that leaves built for higher rates of gas exchange have smaller stomata and faster dynamic characteristics. With the aid of a stomatal control model, it is demonstrated that higher g (op) can potentially expose plants to larger tissue water potential gradients, and that faster stomatal response times can help offset this risk.

Linking hydraulic conductivity and photosynthesis to water-source partitioning in trees versus seedlings.

The relationships between hydraulic and photosynthetic properties in plants have been widely studied, but much less is known about how these properties are linked to water-source partitioning, the spatial and temporal separation of water sources in ecosystems. Plant water-source partitioning is often influenced by the proximity of groundwater from the natural surface. We studied the water acquisition strategy and hydraulic and photosynthetic properties of Tuart (Eucalyptus gomphocephala D.C.), a large coastal tree species that occupies seasonally dry habitats underlain by superficial aquifers. Our goal was to quantify water-source partitioning as the proportion of xylem water derived from the vadose and saturated zones with respect to stage of development and proximity of groundwater. We then sought to associate the proportional contribution of a given water source with xylem hydraulic and photosynthetic properties, thus conferring a linkage. Seedlings were more inclined to use surface soil water when rainfall recharge of the upper profile occurred, suggesting that they maintained or rapidly developed a proportionally high amount of functional roots in the upper, seasonally dry, soil profile. This strategy was associated with a lower xylem-area-specific hydraulic conductivity (K(S)), leaf-area-specific hydraulic conductivity (K(L)) and maximum photon yield of photosystem II (F(V)/F(M)). In contrast, trees acquired water from a variety of sources in different seasons and had a higher K(S), K(L) and F(V)/F(M). Despite the higher K(S) and K(L) in trees, the midday hydrodynamic water potential gradient from soil to leaves, ΔΨ, was similar. We conclude that there was a linkage between hydraulic and photosynthetic properties with the partitioning of water sources and that this adaptation to long-term hydrological regimes accommodated the different hydraulic characteristics and hydrological environments of trees versus seedlings.

Plasticity in maximum stomatal conductance constrained by negative correlation between stomatal size and density: an analysis using Eucalyptus globulus.

Maximum stomatal conductance to water vapour and CO2 (gwmax, gcmax, respectively), which are set at the time of leaf maturity, are determined predominantly by stomatal size (S) and density (D). In theory, many combinations of S and D yield the same gwmax and gcmax, so there is no inherent correlation between S and D, or between S, D and maximum stomatal conductance. However, using basic equations for gas diffusion through stomata of different sizes, we show that a negative correlation between S and D offers several advantages, including plasticity in gwmax and gcmax with minimal change in epidermal area allocation to stomata. Examination of the relationship between S and D in Eucalyptus globulus seedlings and coppice shoots growing in the field under high and low rainfall revealed a strong negative relationship between S and D, whereby S decreased with increasing D according to a negative power function. The results provide evidence that plasticity in maximum stomatal conductance may be constrained by a negative S versus D relationship, with higher maximum stomatal conductance characterized by smaller S and higher D, and a tendency to minimize change in epidermal space allocation to stomata as S and D vary.

A comparison of growth, photosynthetic capacity and water stress in Eucalyptus globulus coppice regrowth and seedlings during early development.

Eucalyptus globulus Labill., a globally significant plantation species, is grown commercially in a multiple rotation framework. Second and subsequent crops of E. globulus may be established either by allowing the cut stumps to resprout (commonly referred to as coppice) or by replanting a new crop of seedlings. Currently, long-term growth data comparing coppice and seedling productivity in second or later rotations in southern Australia is limited. The capacity to predict productivity using these tools is dependent on an understanding of the physiology of seedlings and coppice in response to light, water and nutrient supply. In this study, we compared the intrinsic (independent of the immediate environment) and native (dependent on the immediate environment) physiology of E. globulus coppice and second-generation seedlings during their early development in the field. Coppice not only grew more rapidly, but also used more water and drew on stored soil water to a depth of at least 4.5 m during the first 2 years of growth, whereas the seedlings only accessed the top 0.9 m of the soil profile. During the same period, there was no significant difference between coppice and seedlings in either their stomatal response to leaf-to-air vapour pressure difference (D) or intrinsic water-use efficiency; CO(2)- and light-saturated rates of photosynthesis were greater in seedlings than that in coppice as were the quantum yield of photosynthesis and total leaf chlorophyll content. Thus, at a leaf scale, seedlings are potentially more productive per unit leaf area than coppice during early development, but this is not realised under ambient conditions. The underlying cause of this inherent difference is discussed in the context of the allocation of resources to above- and below-ground organs during early development.

Anisohydric but isohydrodynamic: seasonally constant plant water potential gradient explained by a stomatal control mechanism incorporating variable plant hydraulic conductance.

Isohydric and anisohydric regulations of plant water status have been observed over several decades of field, glasshouse and laboratory studies, yet the functional significance and mechanism of both remain obscure. We studied the seasonal trends in plant water status and hydraulic properties in a natural stand of Eucalyptus gomphocephala through cycles of varying environmental moisture (rainfall, groundwater depth, evaporative demand) in order to test for isohydry and to provide physiological information for the mechanistic interpretation of seasonal trends in plant water status. Over a 16 month period of monitoring, spanning two summers, midday leaf water potential (psi(leaf)) correlated with predawn psi(leaf), which was correlated with water table depth below ground level, which in turn was correlated with total monthly rainfall. Eucalyptus gomphocephala was therefore not seasonally isohydric. Despite strong stomatal down-regulation of transpiration rate in response to increasing evaporative demand, this was insufficient to prevent midday psi(leaf) from falling to levels below -2 MPa in the driest month, well into the region likely to induce xylem air embolisms, based on xylem vulnerability curves obtained in the study. However, even though midday psi(leaf) varied by over 1.2 MPa across seasons, the hydrodynamic (transpiration-induced) water potential gradient from roots to shoots (delta psi(plant)), measured as the difference between predawn and midday psi(leaf), was relatively constant across seasons, averaging 0.67 MPa. This unusual pattern of hydraulic regulation, referred to here as isohydrodynamic, is explained by a hydromechanical stomatal control model where plant hydraulic conductance is dependent on transpiration rate.

Divergent routes to oral cancer.

Most head and neck squamous cell carcinoma (HNSCC) patients present with late-stage cancers, which are difficult to treat. Therefore, early diagnosis of high-risk premalignant lesions and incipient cancers is important. HNSCC is currently perceived as a single progression mechanism, resulting in immortal invasive cancers. However, we have found that approximately 40% of primary oral SCCs are mortal in culture, and these have a better prognosis. About 60% of oral premalignancies (dysplasias) are also mortal. The mortal and immortal tumors are generated in vivo as judged by p53 mutations and loss of p16(INK4A) expression being found only in the original tumors from which the immortal cultures were derived. To investigate the relationships of dysplasias to SCCs, we did microarray analysis of primary cultures of 4 normal oral mucosa biopsies, 19 dysplasias, and 16 SCCs. Spectral clustering using the singular value decomposition and other bioinformatic techniques showed that development of mortal and immortal SCCs involves distinct transcriptional changes. Both SCC classes share most of the transcriptional changes found in their respective dysplasias but have additional changes. Moreover, high-risk dysplasias that subsequently progress to SCCs more closely resemble SCCs than nonprogressing dysplasias. This indicates for the first time that there are divergent mortal and immortal pathways for oral SCC development via intermediate dysplasias. We believe that this new information may lead to new ways of classifying HNSCC in relation to prognosis.

Home care outsourcing strategy.

PURPOSE: This paper aims to help public sector managers that are formulating strategies for outsourcing home care from the independent sector. DESIGN/METHODOLOGY/APPROACH: A review was performed of relevant literature on the outsourcing of home care and its political drivers in the U.K. This indicates that the future of home care services, taking into consideration outsourcing and how Best Value will be achieved, has not been researched widely. Therefore, an exploratory approach to research was adopted here using in-depth analysis of a small number of particularly informative local authorities and private providers selected by purposive/judgemental (extreme and critical case) sampling. Personal contact was deemed necessary in order to perform an intensive investigation to pursue in-depth information. FINDINGS: The British Government's Best Value regime is driving local authorities towards increasing levels of outsourcing in the provision of home care. A local authority may choose to outsource all of its home care or maintain some in-house provision based on capacity or capabilities that are complementary to those provided by the independent sector. The 100 per cent outsourcing strategy places enabling demands on the local authority, whereas the alternative strategy requires decisions to be made on what should be outsourced. Across the authorities surveyed, six strategies for creating a mixed economy of care have been identified, with the mix being based on complementary capacity and/or capabilities. With Best Value driving authorities to consider lower-cost options, the outcome may be a reduction in the amount of complementary capacity provided in-house, in favour of strategies involving complementary capabilities that deliver the Best Value possible. Re-enablement is emerging as a common, complementary or core capability that is remaining in-house. Outsourcing also requires decisions to be made on the number of independent providers to be used and the type of contracts to be employed. This paper considers the decisions that have been made in the local authorities surveyed and critiques the alternative home care outsourcing strategies so derived. RESEARCH LIMITATIONS/IMPLICATIONS: To date, the research has focused on Wales in general plus a few local authorities in England. The next stage will be to survey England in more detail along with other countries that are implementing substantial outsourcing of home care, such as Canada. PRACTICAL IMPLICATIONS: This paper provides timely guidance to public sector and health care managers seeking Best Value in home care through outsourcing. ORIGINALITY/VALUE: Little has been found in the literature on strategies for outsourcing home care, yet such strategies are needed urgently in the U.K. to achieve Best Value. The World Health Organization stresses that strategies should be drawn up for providing support to patients and carers at community level in order to avoid costly institutional care.

A novel strategy for the development of selective active-site inhibitors of the protein tyrosine phosphatase-like proteins islet-cell antigen 512 (IA-2) and phogrin (IA-2beta).

Islet-cell antigen 512 (IA-2) and phogrin (IA-2beta) are atypical members of the receptor protein tyrosine phosphatase (PTP) family that are characterized by a lack of activity against conventional PTP substrates. The physiological role(s) of these proteins remain poorly defined, although recent studies indicate that IA-2 may be involved in granule trafficking and exocytosis. To further understand their function, we have embarked upon developing low-molecular-mass inhibitors of IA-2 and IA-2beta. Previously, we have shown that a general PTP inhibitor, 2-(oxalylamino)benzoic acid (OBA), can be developed into highly selective and potent inhibitors of PTP1B. However, since wild-type IA-2 and IA-2beta lack conventional PTP activity, a novel strategy was designed whereby catalytically active species were generated by 'back-mutating' key non-consensus catalytic region residues to those of PTP1B. These mutants were then used as tools with which to test the potency and selectivity of OBA and a variety of its derivatives. Catalytically competent IA-2 and IA-2beta species were generated by 'back-mutation' of only three key residues (equivalent to Tyr(46), Asp(181) and Ala(217) using the human PTP1B numbering) to those of PTP1B. Importantly, enzyme kinetic analyses indicated that the overall fold of both mutant and wild-type IA-2 and IA-2beta was similar to that of classic PTPs. In particular, one derivative of OBA, namely 7-(1,1-dioxo-1 H -benzo[ d ]isothiazol-3-yloxymethyl)-2-(oxalylamino)-4,7-dihydro-5 H -thieno[2,3- c ]pyran-3 -carboxylic acid ('Compound 6 ' shown in the main paper), which inhibited IA-2beta((S762Y/Y898P/D933A)) (IA-2beta in which Ser(762) has been mutated to tyrosine, Tyr(898) to proline, and Asp(933) to alanine) with a K (i) value of approximately 8 microM, appeared ideal for future lead optimization. Thus molecular modelling of this classical, competitive inhibitor in the catalytic site of wild-type IA-2beta identified two residues (Ser(762) and Asp(933)) that offer the possibility for unique interaction with an appropriately modified 'Compound 6 '. Such a compound has the potential to be a highly selective and potent active-site inhibitor of wild-type IA-2beta.