Tunable Pnictogen Bonding at the Service of Hydroxide Transport across Phospholipid Bilayers.

Our growing interest in the design of pnictogen-based strategies for anion transport has prompted an investigation into the properties of three simple triarylcatecholatostiboranes (1-3) of the general formula (o-C6Cl4O2)SbAr3 with Ar = Ph (1), o-tolyl (2), and o-xylyl (3) for the complexation and transport of hydroxide across phospholipid bilayers. A modified hydroxypyrene-1,3,6-trisulfonic acid (HPTS) assay carried out in artificial liposomes shows that 1 and 2 are potent hydroxide transporters while 3 is inactive. These results indicate that the steric hindrance imposed by the three o-xylyl groups prevents access by the hydroxide anion to the antimony center. Supporting this interpretation, 1 and 2 quickly react with TBAOH·30 H2O ([TBA]+ = [nBu4N]+) to form the corresponding hydroxoantimonate salts [nBu4N][1-OH] and [nBu4N][2-OH], whereas 3 resists hydroxide coordination and remains unperturbed. Moreover, the hydroxide transport activities of 1 and 2 are correlated to the +V oxidation state of the antimony atom as the parent trivalent stibines show no hydroxide transport activity.

Binding, Sensing, And Transporting Anions with Pnictogen Bonds: The Case of Organoantimony Lewis Acids.

Motivated by the discovery of main group Lewis acids that could compete or possibly outperform the ubiquitous organoboranes, several groups, including ours, have engaged in the chemistry of Lewis acidic organoantimony compounds as new platforms for anion capture, sensing, and transport. Principal to this approach are the intrinsically elevated Lewis acidic properties of antimony, which greatly favor the addition of halide anions to this group 15 element. The introduction of organic substituents to the antimony center and its oxidation from the + III to the + V state provide for tunable Lewis acidity and a breadth of applications in supramolecular chemistry and catalysis. The performances of these antimony-based Lewis acids in the domain of anion sensing in aqueous media illustrate the favorable attributes of antimony as a central element. At the same time, recent advances in anion binding catalysis and anion transport across phospholipid membranes speak to the numerous opportunities that lie ahead in the chemistry of these unique main group compounds.

SMART Silly Putty: Stretchable, Malleable, Adherable, Reusable, and Tear-Resistible Hydrogels.

Cell engineering, soft robotics, and wearable electronics often desire soft materials that are easy to deform, self-heal readily, and can relax stress rapidly. Hydrogels, a type of hydrophilic networks, are such kind of materials that can be made responsive to environmental stimuli. However, conventional hydrogels often suffer from poor stretchability and repairability. Here, hydrogels consisting of boronic ester dynamic covalent bonds in a double network of poly(vinyl alcohol)/boric acid and chitosan are synthesized, which demonstrate extreme stretchability (up to 310 times the original length), instant self-healing (within 5 s), and reusability and inherent adhesion. Their instant stress relaxation stems from a low activation energy of the boronic ester bond exchange (≤20 kJ mol-1 ) and contributes to the extreme stretchability and self-healing behaviors. Various water-dispersible additives can be readily incorporated in the hydrogels via hand kneading for potential applications such as soft electronics, bio-signal sensing, and soft artificial joints.

Exploring metapopulation-scale suppression alternatives for a global invader in a river network experiencing climate change.

Invasive species can dramatically alter ecosystems, but eradication is difficult, and suppression is expensive once they are established. Uncertainties in the potential for expansion and impacts by an invader can lead to delayed and inadequate suppression, allowing for establishment. Metapopulation viability models can aid in planning strategies to improve responses to invaders and lessen invasive species' impacts, which may be particularly important under climate change. We used a spatially explicit metapopulation viability model to explore suppression strategies for ecologically damaging invasive brown trout (Salmo trutta), established in the Colorado River and a tributary in Grand Canyon National Park. Our goals were to estimate the effectiveness of strategies targeting different life stages and subpopulations within a metapopulation; quantify the effectiveness of a rapid response to a new invasion relative to delaying action until establishment; and estimate whether future hydrology and temperature regimes related to climate change and reservoir management affect metapopulation viability and alter the optimal management response. Our models included scenarios targeting different life stages with spatially varying intensities of electrofishing, redd destruction, incentivized angler harvest, piscicides, and a weir. Quasi-extinction (QE) was obtainable only with metapopulation-wide suppression targeting multiple life stages. Brown trout population growth rates were most sensitive to changes in age 0 and large adult mortality. The duration of suppression needed to reach QE for a large established subpopulation was 12 years compared with 4 with a rapid response to a new invasion. Isolated subpopulations were vulnerable to suppression; however, connected tributary subpopulations enhanced metapopulation persistence by serving as climate refuges. Water shortages driving changes in reservoir storage and subsequent warming would cause brown trout declines, but metapopulation QE was achieved only through refocusing and increasing suppression. Our modeling approach improves understanding of invasive brown trout metapopulation dynamics, which could lead to more focused and effective invasive species suppression strategies and, ultimately, maintenance of populations of endemic fishes.

Las especies invasoras pueden alterar dramáticamente un ecosistema, pero erradicarlas es complicado y suprimirlas es costoso una vez que están establecidas. Las incertidumbres en el potencial de expansión y el impacto de un invasor pueden derivar en una supresión retardada e inadecuada que permite el establecimiento. Los modelos de viabilidad meta poblacional pueden auxiliar en la planeación de estrategias para mejorar las respuestas ante especies invasoras y disminuir su impacto, lo cual puede ser particularmente importante ante el cambio climático. Usamos un modelo meta poblacional espacialmente explícito para explorar las estrategias de supresión usadas con la trucha café (Salmo trutta), una especie invasora y dañina establecida en el Río Colorado en el Parque Nacional del Gran Cañón. Nuestros objetivos fueron estimar la efectividad de las estrategias enfocadas en diferentes etapas de vida y subpoblaciones dentro de una meta población; cuantificar la efectividad de una respuesta rápida ante una nueva invasión en relación a retardar la acción hasta que ocurra el establecimiento; y estimar si los sistemas térmicos e hidrológicos relacionados con el cambio climático y la gestión de cuencas afectarán la viabilidad meta poblacional y alterarán la respuesta óptima de gestión en el futuro. Nuestros modelos incluyeron escenarios enfocados en diferentes etapas de vida con intensidades espacialmente variables de pesca eléctrica, destrucción de redes, cultivo incentivado de pescadores, piscicidas y un dique. La cuasi extinción (CE) sólo se obtuvo con una supresión a nivel meta poblacional enfocada en múltiples etapas de vida. Las tasas de crecimiento poblacional de la trucha fueron más sensibles a los cambios en edad cero y una gran mortalidad adulta. La duración de la supresión requerida para llegar a la CE para una subpoblación grande establecida fue de doce años en comparación con los cuatro de una respuesta rápida a una nueva invasión. Las subpoblaciones aisladas fueron vulnerables a la supresión; sin embargo, las subpoblaciones conectadas por medio de tributarios incrementaron la persistencia meta poblacional al fungir como refugios climáticos. La escasez de agua, cambios impulsores en el almacenamiento de la cuenca y el calentamiento subsecuente causarían declinaciones de la trucha, pero la CE meta poblacional sólo se logró con el reenfoque e incremento de la supresión. Nuestra estrategia de modelado mejora el entendimiento de las dinámicas meta poblacionales de la trucha café invasora, lo cual podría llevar a estrategias de supresión más enfocadas y efectivas y, finalmente, al mantenimiento de las poblaciones de peces endémicos. Exploración de alternativas a la supresión a escala meta poblacional de un invasor mundial en una red de ríos que experimenta el cambio climático.

Chemical weathering as a mechanism for the climatic control of bedrock river incision.

Feedbacks between climate, erosion and tectonics influence the rates of chemical weathering reactions, which can consume atmospheric CO2 and modulate global climate. However, quantitative predictions for the coupling of these feedbacks are limited because the specific mechanisms by which climate controls erosion are poorly understood. Here we show that climate-dependent chemical weathering controls the erodibility of bedrock-floored rivers across a rainfall gradient on the Big Island of Hawai'i. Field data demonstrate that the physical strength of bedrock in streambeds varies with the degree of chemical weathering, which increases systematically with local rainfall rate. We find that incorporating the quantified relationships between local rainfall and erodibility into a commonly used river incision model is necessary to predict the rates and patterns of downcutting of these rivers. In contrast to using only precipitation-dependent river discharge to explain the climatic control of bedrock river incision, the mechanism of chemical weathering can explain strong coupling between local climate and river incision.

Time Evolution of the Skin-Electrode Interface Impedance under Different Skin Treatments.

A low and stable impedance at the skin-electrode interface is key to high-fidelity acquisition of biosignals, both acutely and in the long term. However, recording quality is highly variable due to the complex nature of human skin. Here, we present an experimental and modeling framework to investigate the interfacial impedance behavior, and describe how skin interventions affect its stability over time. To illustrate this approach, we report experimental measurements on the skin-electrode impedance using pre-gelled, clinical-grade electrodes in healthy human subjects recorded over 24 h following four skin treatments: (i) mechanical abrasion, (ii) chemical exfoliation, (iii) microporation, and (iv) no treatment. In the immediate post-treatment period, mechanical abrasion yields the lowest initial impedance, whereas the other treatments provide modest improvement compared to untreated skin. After 24 h, however, the impedance becomes more uniform across all groups (<20 kΩ at 10 Hz). The impedance data are fitted with an equivalent circuit model of the complete skin-electrode interface, clearly identifying skin-level versus electrode-level contributions to the overall impedance. Using this model, we systematically investigate how time and treatment affect the impedance response, and show that removal of the superficial epidermal layers is essential to achieving a low, long-term stable interface impedance.

Toward a Molecular Understanding of the Impact of Crystal Size and Shape on Punch Sticking.

Punch sticking during tablet manufacturing is a common problem facing the pharmaceutical industry. Using several model compounds, effects of crystal size and shape of active pharmaceutical ingredients (API) on punch sticking propensity were systematically investigated in this work to provide molecular insights into the punch-sticking phenomenon. In contrast to the common belief that smaller API particles aggravate punch sticking, results show that particle size reduction can either reduce or enhance API punch sticking, depending on the complex interplay among the particle surface area, plasticity, cohesive strength, and specific surface functional groups. Therefore, other factors, such as crystal mechanical properties, surface chemistry of crystal facets exposed to the punch face, and choice of excipients in a formulation, should be considered for a more reliable prediction of the initiation and progression of punch sticking. The exposure of strong electronegative groups to the punch face facilitates the onset of sticking, while higher plasticity and cohesive strength aggravate sticking.

Formula supplementation remains a risk for cow's milk allergy in breast-fed infants.

BACKGROUND: Many breastfed babies in Ireland receive formula supplementation within 24 hours of birth. We explored (a) impact of formula supplementation on the likelihood of developing cow's milk protein allergy (CMPA) and (b) current practice of formula supplementation (<24 hours) among mothers intending to breastfeed. METHOD: Fifty-five CMPA-diagnosed children, fed at <24 hours of age (breast only, formula only or breast with formula supplementation), were recruited, and 55 milk-tolerant age- and sex-matched controls were identified retrospectively in Cork University Maternity Hospital. Two logistic regressions (LoR) examined neonatal feed types on likelihood of developing CMPA while controlling for parental atopy and infant sex. Formula supplementation was then prospectively measured among a separate group of 179 breastfeeding mothers. Linear regression (LiR) analysis was used to examine the subjective and objective reasons for formula supplementation, in addition to examining pre-existing factors. RESULTS: Two LoR examined the infant groups: exclusively breastfed, exclusively formula-fed or breastfed with formula supplementation. The first LoR model which showed only formula supplementation was significant in prediction of development of CMPA (χ2 (3) = 25.74, P < .05), with 74% diagnostic accuracy when parental atopy and infant sex were controlled for. Breastfed infants given formula supplements were 7.03 (95% CI, 1.82-27.25) times more likely to exhibit CMPA than those who were exclusively breastfed. Formula supplementation was significant (OR 16.62, 95% CI 3.89-71.11), indicating that breastfed infants who were given formula supplements were 16 times more likely to exhibit CMPA than those who were exclusively bottle-fed. Exclusively formula-fed infants (odds ratio 0.42, 95% CI, 0.16-1.07) were not significantly more likely to exhibit CMPA than those who were exclusively breastfed in either model (P > .05). About 45.8% of breastfed infants (<24 hours) received supplemental formula. LiR investigated importance of the subjective and objective reasons, in predicting formula supplementation. This model was significant F(8,170) = 66.95, P < .05) explaining 75% of total variance. The subjective factors 'no latch' and 'mum unwell' were the strongest predictors (ß > .45). Objective factors and pre-existing factors had lower ß values with only mode of delivery and infant hypoglycaemia being significant. CONCLUSION: Breastfed babies are still being put at significantly increased risk of CMPA by receiving supplemental formula in the first 24 hours of life, despite the major predictors of supplementation being subjective and remediable in other ways. Mothers and healthcare providers should be better educated on the benefits of exclusive breastfeeding and resourced adequately to avoid unnecessary formula supplementation to reduce risk of development of CMPA.

Is Poor Hamstring Flexibility a Risk Factor for Hamstring Injury in Gaelic Games?

CONTEXT: Hamstring injuries are a leading cause of injury in Gaelic games. Hamstring flexibility as a risk factor for hamstring injury has not yet been examined prospectively in Gaelic games. OBJECTIVE: To examine whether hamstring flexibility, using the modified active knee extension (AKE) test, and previous injury are risk factors for hamstring injury in Gaelic players and to generate population-specific AKE cutoff points. DESIGN: Prospective cohort study. SETTING: School and colleges. Patients (or Other Participants): Adolescent and collegiate Gaelic footballers and hurlers (n = 570). INTERVENTION(S): The modified AKE test was completed at preseason, and hamstring injuries were assessed over the course of one season. Any previous hamstring injuries were noted in those who presented with a hamstring injury. MAIN OUTCOME MEASURES: Bilateral AKE scores and between-leg asymmetries were recorded. Receiver operating characteristic curves were implemented to generate cutoff points specific to Gaelic players. Univariate and backward stepwise logistic regression analyses were completed to predict hamstring injuries, hamstring injuries on the dominant leg, and hamstring injuries on the nondominant leg. RESULTS: Mean flexibility of 64.2° (12.3°) and 64.1° (12.4°) was noted on the dominant and nondominant leg, respectively. Receiver operating characteristic curves generated a cutoff point of < 65° in the AKE on the nondominant leg only. When controlled for age, AKE on the nondominant leg was the only predictor variable left in the multivariate model (odds ratio = 1.03) and significantly predicted hamstring injury (χ2 = 9.20, P = .01). However, the sensitivity was 0% and predicted the same amount of cases as the null model. It was not possible to generate a significant model for hamstring injuries on the dominant leg (P > .05), and no variables generated a P value < .20 in the univariate analysis on the nondominant leg. CONCLUSIONS: Poor flexibility noted in the AKE test during preseason screening and previous injury were unable to predict those at risk of sustaining a hamstring strain in Gaelic games with adequate sensitivity.

The viability of probiotics in water, breast milk, and infant formula.

The aim of this study was to determine bacteriological stability of a probiotic mixture dispersed in various diluents. The commercially available probiotic (Infloran®), containing Bifidobacterium bifidum (109 CFU/250 mg tablet) and Lactobacillus acidophilus (109 CFU/250 mg tablet), was dispersed within expressed breast milk, sterile water, and infant formula and examined at temperatures of 4 and 21 °C. When stored at 4 °C, significant decreases (P < 0.05) in the level of L. acidophilus and B. bifidum were observed in expressed breast milk and sterile water after a 6-h period. However, when stored in infant formula, both strains remained stable over a 12-h period. When stored at 21 °C, a significant decrease (P < 0.05) was observed in the level of L. acidophilus in sterile water, expressed breast milk and infant formula throughout a 12-h period. However, no significant decrease was observed overtime in B. bifidum in all three diluents at this temperature. CONCLUSION: Our findings suggest that, when stored at 4 °C, this probiotic product can remain at a stable condition for 6 h in sterile water and infant formula; however, the viability of the probiotic decreases significantly after this period of time. Administration of this probiotic in sterile water can be an acceptable alternative to dispersion and administration in expressed breast milk. What is Known: • Administration of probiotics containing lactobacilli and bifidobacteria has become more widespread in neonatology, mainly as prophylaxis for the prevention of necrotising entercolitis in preterm infants. • Probiotic reconstitution, from its powder base, is not standardized and various diluents, including sterile water, breast milk, and infant formula, have been used. What is New: • When stored at 4 °C, a probiotic containing lactobacilli and bifidobacteria remains at a stable microbological condition for up to 6 h in sterile water. • Administration of this probiotic dispersed in sterile water, followed by an EBM feed, can be an acceptable alternative to dispersion and administration in EBM.

In Vitro Anticancer Activity and in Vivo Biodistribution of Rhenium(I) Tricarbonyl Aqua Complexes.

Seven rhenium(I) complexes of the general formula fac-[Re(CO)3(NN)(OH2)]+ where NN = 2,2'-bipyridine (8), 4,4'-dimethyl-2,2'-bipyridine (9), 4,4'-dimethoxy-2,2'-bipyridine (10), dimethyl 2,2'-bipyridine-4,4'-dicarboxylate (11), 1,10-phenanthroline (12), 2,9-dimethyl-1,10-phenanthroline (13), or 4,7-diphenyl-1,10-phenanthroline (14), were synthesized and characterized by 1H NMR spectroscopy, IR spectroscopy, mass spectrometry, and X-ray crystallography. With the exception of 11, all complexes exhibited 50% growth inhibitory concentration (IC50) values that were less than 20 µM in HeLa cells, indicating that these compounds represent a new potential class of anticancer agents. Complexes 9, 10, and 13 were as effective in cisplatin-resistant cells as wild-type cells, signifying that they circumvent cisplatin resistance. The mechanism of action of the most potent complex, 13, was explored further by leveraging its intrinsic luminescence properties to determine its intracellular localization. These studies indicated that 13 induces cytoplasmic vacuolization that is lysosomal in nature. Additional in vitro assays indicated that 13 induces cell death without causing an increase in intracellular reactive oxygen species or depolarization of the mitochondrial membrane potential. Further studies revealed that the mode of cell death does not fall into one of the canonical categories such as apoptosis, necrosis, paraptosis, and autophagy, suggesting that a novel mode of action may be operative for this class of rhenium compounds. The in vivo biodistribution and metabolism of complex 13 and its 99mTc analogue 13* were also evaluated in naïve mice. Complexes 13 and 13* exhibited comparable biodistribution profiles with both hepatic and renal excretion. High-performance liquid chromatography inductively coupled plasma mass-spectrometry (HPLC-ICP-MS) analysis of mouse blood plasma and urine postadministration showed considerable metabolic stability of 13, rendering this potent complex suitable for in vivo applications. These studies have shown the biological properties of this class of compounds and demonstrated their potential as promising theranostic anticancer agents that can circumvent cisplatin resistance.

Quetiapine v. lithium in the maintenance phase following a first episode of mania: randomised controlled trial.

BackgroundLithium and quetiapine are considered standard maintenance agents for bipolar disorder yet it is unclear how their efficacy compares with each other.AimsTo investigate the differential effect of lithium and quetiapine on symptoms of depression, mania, general functioning, global illness severity and quality of life in patients with recently stabilised first-episode mania.MethodMaintenance trial of patients with first-episode mania stabilised on a combination of lithium and quetiapine, subsequently randomised to lithium or quetiapine monotherapy (up to 800 mg/day) and followed up for 1 year. (Trial registration: Australian and New Zealand Clinical Trials Registry - ACTRN12607000639426.)ResultsIn total, 61 individuals were randomised. Within mixed-model repeated measures analyses, significant omnibus treatment × visit interactions were observed for measures of overall psychopathology, psychotic symptoms and functioning. Planned and post hoc comparisons further demonstrated the superiority of lithium treatment over quetiapine.ConclusionsIn people with first-episode mania treated with a combination of lithium and quetiapine, continuation treatment with lithium rather than quetiapine is superior in terms of mean levels of symptoms during a 1-year evolution.

Analysis of population inquiry on practices for ultraviolet radiation protection.

UV radiation exposure is one of the key modifiable risk factors for skin cancer. Hence, patient education regarding skin protection and sunscreen use is of tremendous importance to public health. To better understand patient practices regarding skin protection in a population level, we looked into the Internet search behavior of the US-based population. We investigated patient inquires on the United States Food and Drug Administration (FDA) announcements regarding sunscreen use by quantifying search terms such as "broad spectrum sunscreen", "sunscreen" and "sunblock" with Google Trends, a novel methodology for understanding internet search practices. Our findings show that "broad spectrum sunscreen" searches were significantly increased post 2011 FDA announcements, which suggest increased public awareness regarding the importance of broad spectrum protection. It is encouraging these preliminary results indicate that skin protection practices are being increasingly investigated by the general public and may serve as a novel approach for identifying areas of improvement regarding patient education on the reduction of the risk for skin cancer.

Two mirror X-ray pulse split and delay instrument for femtosecond time resolved investigations at the LCLS free electron laser facility.

We built a two-mirror based X-ray split and delay (XRSD) device for soft X-rays at the Linac Coherent Light Source free electron laser facility. The instrument is based on an edge-polished mirror design covering an energy range of 250 eV-1800 eV and producing a delay between the two split pulses variable up to 400 femtoseconds with a sub-100 attosecond resolution. We present experimental and simulation results regarding molecular dissociation dynamics in CH3I and CO probed by the XRSD device. We observed ion kinetic energy and branching ratio dependence on the delay times which were reliably produced by the XRSD instrument.

Seizure burden and neurodevelopmental outcome in neonates with hypoxic-ischemic encephalopathy.

AIM: To examine the relationship between electrographic seizures and long-term outcome in neonates with hypoxic-ischemic encephalopathy (HIE). METHOD: Full-term neonates with HIE born in Cork University Maternity Hospital from 2003 to 2006 (pre-hypothermia era) and 2009 to 2012 (hypothermia era) were included in this observational study. All had early continuous electroencephalography monitoring. All electrographic seizures were annotated. The total seizure burden and hourly seizure burden were calculated. Outcome (normal/abnormal) was assessed at 24 to 48 months in surviving neonates using either the Bayley Scales of Infant and Toddler Development, Third Edition or the Griffiths Mental Development Scales; a diagnosis of cerebral palsy or epilepsy was also considered an abnormal outcome. RESULTS: Continuous electroencephalography was recorded for a median of 57.1 hours (interquartile range 33.5-80.5h) in 47 neonates (31 males, 16 females); 29 out of 47 (62%) had electrographic seizures and 25 out of 47 (53%) had an abnormal outcome. The presence of seizures per se was not associated with abnormal outcome (p=0.126); however, the odds of an abnormal outcome increased over ninefold (odds ratio [OR] 9.56; 95% confidence interval [95% CI] 2.43-37.67) if a neonate had a total seizure burden of more than 40 minutes (p=0.001), and eightfold (OR: 8.00; 95% CI: 2.06-31.07) if a neonate had a maximum hourly seizure burden of more than 13 minutes per hour (p=0.003). Controlling for electrographic HIE grade or treatment with hypothermia did not change the direction of the relationship between seizure burden and outcome. INTERPRETATION: In HIE, a high electrographic seizure burden is significantly associated with abnormal outcome, independent of HIE severity or treatment with hypothermia.

Mode of neonatal death in an Irish maternity centre.

UNLABELLED: Modes of neonatal dying vary among maternity centres, both within and between countries. There have been few reports concerning mode of dying from countries with low rates of termination of pregnancy, such as Ireland. We conducted a retrospective chart review of all neonatal deaths, between January 2010 and January 2013, within a single Irish maternity centre. The mode of dying was classified as one of (1) withholding life-sustaining treatment (LST), (2) withdrawal of LST in moribund infants, (3) withdrawal of LST for quality of life reasons or (4) death despite maximal intensive care treatment. There were a total of 64 deaths during the study period. Congenital abnormalities accounted for 47 % of deaths and prematurity for 41 % of deaths. Withholding LST was the most frequent mode of dying, occurring in 38 % of all deaths. A total of 12 % of neonatal deaths occurred despite maximal intensive care treatment. CONCLUSIONS: Congenital abnormalities were the most common cause of neonatal deaths. A high proportion followed LST being withheld, most likely a reflection of the low rates of medical termination in Ireland. Modes of dying in the neonatal period vary between maternity centres with culturally different backgrounds.

Double-core-hole spectroscopy for chemical analysis with an intense X-ray femtosecond laser.

Theory predicts that double-core-hole (DCH) spectroscopy can provide a new powerful means of differentiating between similar chemical systems with a sensitivity not hitherto possible. Although DCH ionization on a single site in molecules was recently measured with double- and single-photon absorption, double-core holes with single vacancies on two different sites, allowing unambiguous chemical analysis, have remained elusive. Here we report that direct observation of double-core holes with single vacancies on two different sites produced via sequential two-photon absorption, using short, intense X-ray pulses from the Linac Coherent Light Source free-electron laser and compare it with theoretical modeling. The observation of DCH states, which exhibit a unique signature, and agreement with theory proves the feasibility of the method. Our findings exploit the ultrashort pulse duration of the free-electron laser to eject two core electrons on a time scale comparable to that of Auger decay and demonstrate possible future X-ray control of physical inner-shell processes.

Discovery of an intravenous hepatoselective glucokinase activator for the treatment of inpatient hyperglycemia.

Glucokinase (hexokinase IV) continues to be a compelling target for the treatment of type 2 diabetes given the wealth of supporting human genetics data and numerous reports of robust clinical glucose lowering in patients treated with small molecule allosteric activators. Recent work has demonstrated the ability of hepatoselective activators to deliver glucose lowering efficacy with minimal risk of hypoglycemia. While orally administered agents require a considerable degree of passive permeability to promote suitable exposures, there is no such restriction on intravenously delivered drugs. Therefore, minimization of membrane diffusion in the context of an intravenously agent should ensure optimal hepatic targeting and therapeutic index. This work details the identification a hepatoselective GKA exhibiting the aforementioned properties.

Introduction of a Single Electronic Health Record for Maternity Units in Ireland: Outline of the Experiences of the Project Management Team.

Electronic health records (EHRs) are being introduced worldwide. The change from paper to electronic records has not always been a seamless or quick process; however, EHRs are viewed as central to updating modern health care, especially organization structures and delivery of sustainable care with the potential for joint decision-making with the patient. The objective of this viewpoint paper is to outline how an EHR is being developed in Ireland. The focus of the Maternal & Newborn Clinical Management System project is the design and implementation of an EHR for all women and babies in the maternity services in the Republic of Ireland. The paper also outlines the lessons learned from the planning to the optimization stage of the project. The paper was developed through discussions with the project management team and their completed reports that outline the lessons they acquired from each project stage. Key lessons learned from each stage of the project are highlighted. This viewpoint paper explains how the national project management team is implementing the EHR and outlines the experiences and lessons learned and the challenges ahead following the phase one introduction. The Maternal & Newborn Clinical Management System is an example of a clinician-led, patient-focused, change management project from its inception to implementation. The introduction of EHRs is essential in modernizing health care and optimizing patient outcomes through the accurate and appropriate use of data.

Effect of the deposition process on the stability of Ti3C2Tx MXene films for bioelectronics.

Ti3C2Tx MXene is emerging as the enabling material in a broad range of wearable and implantable medical technologies, thanks to its outstanding electrical, electrochemical, and optoelectronic properties, and its compatibility with high-throughput solution-based processing. While the prevalence of Ti3C2Tx MXene in biomedical research, and in particular bioelectronics, has steadily increased, the long-term stability and degradation of Ti3C2Tx MXene films have not yet been thoroughly investigated, limiting its use for chronic applications. Here, we investigate the stability of Ti3C2Tx films and electrodes under environmental conditions that are relevant to medical and bioelectronic technologies: storage in ambient atmosphere (shelf-life), submersion in saline (akin to the in vivo environment), and storage in a desiccator (low-humidity). Furthermore, to evaluate the effect of the MXene deposition method and thickness on the film stability in the different conditions, we compare thin (25 nm), and thick (1.0 µm) films and electrodes fabricated via spray-coating and blade-coating. Our findings indicate that film processing method and thickness play a significant role in determining the long-term performance of Ti3C2Tx films and electrodes, with highly aligned, thick films from blade coating remarkably retaining their conductivity, electrochemical impedance, and morphological integrity even after 30 days in saline. Our extensive spectroscopic analysis reveals that the degradation of Ti3C2Tx films in high-humidity environments is primarily driven by moisture intercalation, ingress, and film delamination, with evidence of only minimal to moderate oxidation.