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BACKGROUND: Common bean (Phaseolus vulgaris) is one of the main nutritional resources in the world, and a low environmental impact source of protein. However, the majority of its cultivation areas are affected by drought and this scenario is only expected to worsen with climate change. Stomatal closure is one of the most important plant responses to drought and the MYB60 transcription factor is among the key elements regulating stomatal aperture. If targeting and mutating the MYB60 gene of common bean would be a valuable strategy to establish more drought-tolerant beans was therefore investigated. RESULTS: The MYB60 gene of common bean, with orthology to the Arabidopsis AtMYB60 gene, was found to have conserved regions with MYB60 typical motifs and architecture. Stomata-specific expression of PvMYB60 was further confirmed by q-RT PCR on organs containing stomata, and stomata-enriched leaf fractions. Further, function of PvMYB60 in promoting stomata aperture was confirmed by complementing the defective phenotype of a previously described Arabidopsis myb60-1 mutant. CONCLUSIONS: Our study finally points PvMYB60 as a potential target for obtaining more drought-tolerant common beans in the present context of climate change which would further greatly contribute to food security particularly in drought-prone countries.

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Potassium (K+) is an essential macronutrient which contributes to osmotic- and turgor-related processes in plants. Calcineurin-B like Interacting Protein Kinases (CIPKs) play crucial roles in plants under low-K+ supply since they activate root K+ uptake transport systems such as AKT1 and AtHAK5. In Arabidopsis, AtCIPK9 is important for low-K+ tolerance since atcipk9 plants exhibited poor growth and leaf chlorosis when K+ was scarce. Part of these phenotypes could be ascribed to the activation of AtHAK5 by AtCIPK9. It has been reported that important differences exist between Arabidopsis and other plant species such as tomato with respect to the regulation of K+ uptake systems. Thus, our aim was to evaluate the contribution of SlCIPK9, the homologous protein of AtCIPK9 in tomato, to K+ nutrition. Unexpectedly, phenotyping experiments carried out with slcipk9 loss-of-function mutants revealed that SlCIPK9 did not play a clear role in tomato K+ homeostasis. By contrast, it was found that SlCIPK9 contributed to pollen tube elongation, but not to pollen germination, via a K+-independent mechanism. Therefore, our results highlight the remarkable differences that exist in Ca2+ signaling pathways between plant species and encourage the realization of more comparative studies as the one presented here.

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SUMMARY: Hand rotation and the ability to apply force and overcome external load are due to the coordinated activity of forearm bones, the interosseous ligament, and involved muscles. The following review is a detailed description of the anatomy and mechanics which illustrates how the forearm works.

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BACKGROUND: O'Driscoll popularized the principle of linked column fixation for distal humerus fractures. Despite the linked column concept being widely accepted, there are few reported techniques to accomplish this goal. A novel device was designed based on the principles of linked columns. An interlocking beam is used to connect the medial and lateral plates, creating a unified fixed angle construct. Our primary objective was to report clinical outcomes across multiple institutions for a linking beam used in distal humerus fracture fixation. METHODS: A retrospective series was collected from 5 institutions for the TiBeam (Skeletal Dynamics) with a minimum follow-up of 6 months. Acute and chronic treatment of distal humerus fracture patterns and all plate configurations were included for analysis. RESULTS: A total of 36 cases were collected at a mean age of 52 years and a mean follow-up of 19.3 months. AO C-type fractures were 56% of the series. The median Mayo Elbow Performance Score was 85 (interquartile range [IQR] 76.3-90), the median DASH was 21.4 (IQR 15.9-30), and the median score on the visual analog scale for pain during activities of daily living was 3.5 (IQR 2-5). An olecranon osteotomy was used in 86% of cases, and an anatomic plate was used for fixation of the osteotomy in 94% of those cases. There were 3 cases of olecranon plate removal for a rate across the series of 13.7%. DISCUSSION: Our short-term results demonstrate satisfactory clinical outcomes with low rates of revision for distal humerus fracture fixed with a linking beam. Further, the rate of removal for the olecranon osteotomy plate was lower than historical reports for aggregate methods of osteotomy fixation.

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Navigating through complex road geometries, such as roundabouts, poses significant challenges and safety risks for drivers. These challenges may be exacerbated when drivers are distracted by mobile phone conversations. The interplay of road geometry, driving state, and driver characteristics in creating compound risks remains an underexplored area in existing literature. Proper understanding of such compound crash risk is not only crucial to improve road geometric design but also to educate young drivers, who are particularly risk-takers and to devise strict penalties for mobile phone usage whilst driving. To fill this gap, this study examines crash risks associated with gap acceptance manoeuvres at roundabouts in the simulated environment of the CARRS-Q driving simulators, where 32 licenced young drivers were exposed to a gap acceptance scenario in three phone conditions: baseline (no phone conversation), handheld, and hands-free. A parametric random parameters survival modelling approach is adopted to understand safety margins-characterised by gap times-during gap acceptance scenarios at roundabouts, concurrently uncover driver-level heterogeneity with mobile phone distraction and capture repeated measures of experiment design. The model specification includes the handheld phone condition as a random parameter and hands-free phone condition, acceleration noise, gap size, crash history, and gender as non-random parameters. Results suggest that the majority of handheld distracted drivers have smaller safety margins, reflecting the negative consequences of engaging in handheld phone conversations. Interestingly, a group of drivers in the same handheld phone condition have been found to exhibit cautious/safer behaviour, as evidenced by longer gap times, reflecting their risk compensation behaviour. Female distracted drivers are also found to exhibit safer gap acceptance behaviour compared to distracted male drivers. The findings of this study shed light on the compound risk of mobile phone distraction and gap acceptance at roundabouts, requiring policymakers and authorities to devise strict penalties and laws for distracted driving.

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Potassium (K+) selectivity of high-affinity K+ uptake systems is crucial for plant growth under low K+ and in the presence of inhibitors of K+ uptake that are toxic to plants such as Na+ or Cs+. Here, we express a mutated version of the Arabidopsis AtHAK5 high-affinity K+ transporter consisting on a change of phenylalanine 130 to serine (F130S) in athak5 akt1 double mutant plants. F130S-expressing plants show better growth, increased K+ uptake from low external concentrations and higher K+ contents when grown at low K+ (10 µM) and when grown at low K+ in the presence of Na+ (15 mM) or Cs+ (1 µM). In addition, these plants accumulate less Na+ and Cs+, resulting in lower Na+/K+ and Cs+/K+ ratios, which are important determinants of plant tolerance to salt stress and to Cs+-polluted soils. Structure analysis of AtHAK5 suggest that the F130 residue approaches the intracellular gate of the K+ tunnel of AtHAK5, affecting somehow its ionic selectivity. Modification of transport systems has a large potential to face challenges of future agriculture such as sustainable production under abiotic stress conditions imposed by climate change.

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BACKGROUND: Cancer survival is a key component to assess the overall effectiveness of healthcare systems in their cancer management efforts. A key supporting tool for planning and decision making was introduced with the development of an index of cancer survival that summarises survival for all adults and cancer types into one single estimate, but the implementation details have not been previously described. METHODS: We detail the construction of the index, including the structure, the calculation of 'sex-age-cancer' specific weights and our proposed modelling strategy to estimate net survival. We provide some practical recommendations through an illustration using a synthetic dataset ('Replica') that we generated for this purpose. An example of R code usage to estimate the index using our approach is provided. RESULTS: The 'Replica' contains 500 000 artificial cancer records that mimic a cohort of adult cancer patients diagnosed with cancer in England between 1980 and 2004. Using this dataset, we estimated an index of cancer survival at one, five, and ten years after diagnosis for five selected periods of diagnosis, and provide an example of interpretation of these results. DISCUSSION: We propose a flexible penalised regression modelling strategy to estimate the index's 'sex-age-cancer' specific cancer survival components that minimises the estimation challenge of these components. This tutorial will support researchers in constructing an index of cancer survival for their own setting, facilitating the enrichment of existing toolkits of cancer indicators to more effectively measure progress against cancer in their respective regions/countries.

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BACKGROUND: The incidence of radial head fractures is increasing, and radial head arthroplasty (RHA) is being more frequently used as treatment for irreparable fractures. Our objective was to compare radiocapitellar pressure between the native joint and 2 radial head prosthesis conditions: (1) a prosthetic head that was aligned to the forearm axis of rotation and (2) the same prosthesis with an axisymmetric nonaligned head. METHODS: Ten cadaveric specimens received a pressfit radial head prosthesis (Align; Skeletal Dynamics) for both prosthetic testing conditions. Anatomic alignment (AL) was defined as the prosthetic head aligned to the forearm axis of rotation. Axisymmetric alignment (AX) was defined as the prosthetic radial head aligned to the axis of the prosthetic stem. Axial load was applied with the elbow in extension and the forearm pronated. Data were collected using a Tekscan 4000 sensor. RESULTS: The mean pressure in the AL and AX groups were significantly higher than the mean pressure in the native joint. Compared with the native joint, the mean pressure was 19% higher in the AL group and 56% higher in the AX group. Peak pressure beyond 5 MPa occurred in 0 specimens in the native joint group, in 1 specimen (10%) in the AL group, and in 5 specimens (50%) in the AX group. DISCUSSION: Our results demonstrated that a pressfit radial head prosthesis aligned with the forearm axis of rotation yields capitellar pressures that were more similar to the native condition than a nonaligned pressfit prosthesis. These findings suggest that anatomic alignment may optimize capitellar wear properties, improving the long-term durability of radial head arthroplasty.

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BACKGROUND: More deprived cancer patients are at higher risk of Emergency Presentation (EP) with most studies pointing to lower symptom awareness and increased comorbidities to explain those patterns. With the example of colon cancer, we examine patterns of hospital emergency admissions (HEAs) history in the most and least deprived patients as a potential precursor of EP. METHODS: We analysed the rates of hospital admissions and their admission codes (retrieved from Hospital Episode Statistics) in the two years preceding cancer diagnosis by sex, deprivation and route to diagnosis (EP, non-EP). To select the conditions (grouped admission codes) that best predict emergency admission, we adapted the purposeful variable selection to mixed-effects logistic regression. RESULTS: Colon cancer patients diagnosed through EP had the highest number of HEAs than all the other routes to diagnosis, especially in the last 7 months before diagnosis. Most deprived patients had an overall higher rate and higher probability of HEA but fewer conditions associated with it. CONCLUSIONS: Our findings point to higher use of emergency services for non-specific symptoms and conditions in the most deprived patients, preceding colon cancer diagnosis. Health system barriers may be a shared factor of socio-economic inequalities in EP and HEAs.

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Relative survival represents the preferred framework for the analysis of population cancer survival data. The aim is to model the survival probability associated with cancer in the absence of information about the cause of death. Recent data linkage developments have allowed for incorporating the place of residence into the population cancer databases; however, modeling this spatial information has received little attention in the relative survival setting. We propose a flexible parametric class of spatial excess hazard models (along with inference tools), named "Relative Survival Spatial General Hazard," that allows for the inclusion of fixed and spatial effects in both time-level and hazard-level components. We illustrate the performance of the proposed model using an extensive simulation study, and provide guidelines about the interplay of sample size, censoring, and model misspecification. We present a case study using real data from colon cancer patients in England. This case study illustrates how a spatial model can be used to identify geographical areas with low cancer survival, as well as how to summarize such a model through marginal survival quantities and spatial effects.

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The beneficial effects of Na+ as a substitute for K+ have been well-documented at the physiological level. However, the transport systems and regulatory mechanisms that allow Na+ acquisition under K+ deficiency remain poorly understood in the majority of land plants. In tomato, SlCIPK23 kinase was involved in Na+ accumulation in K+-starved plants, in addition to activating the LKT1 K+ channel and the K+ transporter SlHAK5. We used the central role of SlCIPK23 in K+ and Na+ acquisition to study which molecular entities mediate Na+ uptake with knockout tomato mutants and expression in heterologous systems. Two main pathways for Na+ uptake were deduced in tomato plants: an NH4+-sensitive pathway dependent on SlCIPK23, and a second one sensitive to Ba2+, Ca2+, La3+, and Li+. The addition of Na+ (10 mM) to lkt1, slhak5, or slcipk23 mutant KO lines produced interesting changes in root morphology. In particular, the roots of slcipk23 plants were longer and lighter than those of the WT under K+-deficient conditions and this effect was reversed by the addition of 10 mM Na+. These results provide a stimulating perspective for the study of the beneficial effects of Na+ in crops.

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Acute-on-chronic liver failure is a syndrome associated with a high short-term mortality rate. Severe systemic inflammation and single- and multiple-organ failure are a hallmark of this syndrome, with pro-inflammatory precipitating events occurring in the liver or extrahepatic regions. We report a case of a 69-year-old man with a previous diagnosis of alcohol-induced liver cirrhosis who presented with a poorly defined, erythematous-purplish, and edematous plaque with multiple hemorrhagic blisters over the left leg, one day after receiving a spider bite. During the following hours, the skin lesion progressed, and the patient developed hepatic encephalopathy, respiratory failure, and arterial hypotension, requiring the administration of vasopressors; blood analysis revealed hypercreatininemia, an elevated international normalized ratio (INR) value, and hyperbilirubinemia. The patient was diagnosed with acute-on-chronic liver failure caused by cutaneous loxoscelism. There was no hemolytic anemia, rhabdomyolysis, or disseminated intravascular coagulation in the patient, thus excluding the possibility of visceral loxoscelism.

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Vehicle handling and stability performance and ride comfort is normally assessed through standard field test procedures, which are time consuming and expensive. However, the rapid development of digital technologies in the automotive industry have enabled to properly model and simulate the full-vehicle dynamics, thus drastically reducing design and manufacturing times and costs while enhancing the performance, safety, and longevity of vehicle systems. This paper focus on a computationally efficient multi-objective optimization framework for developing an optimal design of a vehicle steering system, which is carried out by coupling certain computer-aided design tools (CAD) and computer-aided engineering (CAE) software. The 3D CAD model of the steering system is made using SolidWorks, the Finite Element Analysis (FEA) is modelled using Ansys Workbench, while the multibody kinematic and dynamic is analysed using Adams/Car. They are embedded in a multidisciplinary optimization design framework (modeFrontier) with the aim of determining the optimal hardpoint locations of the suspension and steering systems. This is achieved by minimizing the Ackermann error and toe angle deviations, together with the volume, mass, and maximum stresses of the rack-and-pinion steering mechanism. This enhances the vehicle stability, safety, manoeuvrability, and passengers' comfort, extends the vehicle systems reliability and fatigue life, while reducing the tire wear. The method has been successfully applied to different driving scenarios and vehicle maneuvers to find the optimal Pareto front and analyse the performance and behaviour of the steering system. Results show that the design of the steering system can be significantly improved using this approach.

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Fractures of the phalanges encompass a wide range of injury patterns with variable articular and soft tissue involvement. The goals of treatment whether conservative or surgical are the restoration of function while limiting the risk of complications. An armamentarium of fixation options allows the surgeon to appropriately treat these fractures with the intention of initiating early postoperative mobilization. Previous publications report variable rates of complications following internal fixation of phalangeal fractures which represents an unsolved problem. It is incumbent on the surgeon to utilize meticulous surgical technique, achieve anatomic reduction with stable fixation and initiate early postoperative mobilization where indicated. In the following text, we review the management of most types of phalangeal fractures, except fracture-dislocations of the proximal interphalangeal joint. These injuries comprise a wide spectrum of presentation; thus, an understanding of anatomical and mechanical principles is integral to achieving a successful outcome.

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We study parametric inference on a rich class of hazard regression models in the presence of right-censoring. Previous literature has reported some inferential challenges, such as multimodal or flat likelihood surfaces, in this class of models for some particular data sets. We formalize the study of these inferential problems by linking them to the concepts of near-redundancy and practical nonidentifiability of parameters. We show that the maximum likelihood estimators of the parameters in this class of models are consistent and asymptotically normal. Thus, the inferential problems in this class of models are related to the finite-sample scenario, where it is difficult to distinguish between the fitted model and a nested nonidentifiable (i.e., parameter-redundant) model. We propose a method for detecting near-redundancy, based on distances between probability distributions. We also employ methods used in other areas for detecting practical nonidentifiability and near-redundancy, including the inspection of the profile likelihood function and the Hessian method. For cases where inferential problems are detected, we discuss alternatives such as using model selection tools to identify simpler models that do not exhibit these inferential problems, increasing the sample size, or extending the follow-up time. We illustrate the performance of the proposed methods through a simulation study. Our simulation study reveals a link between the presence of near-redundancy and practical nonidentifiability. Two illustrative applications using real data, with and without inferential problems, are presented.

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We describe a medial approach to the coronoid where the flexor-pronator mass is released from its humeral origin by creating a proximally based tendinous flap. This technique facilitates access to the coronoid, preservation of the medial collateral ligament origin, and repair of the flexor-pronator mass. This approach has utility for all coronoid fracture variations but especially the O'Driscoll anteromedial subtype 3, which includes fractures of the sublime tubercle, the anteromedial facet, and the coronoid tip.

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To reduce the breast cancer burden, the French National Organised Breast Cancer Screening Programme (FNOBCSP) was implemented in 2004. The recommended participation rate has never been achieved and socio-territorial inequities in participation have been reported on several occasions. We investigated the functional forms and consistency of the relationships between neighbourhood deprivation, travel time to the nearest accredited radiology centre and screening uptake. We used two-level hierarchical generalised additive models in 8 types of territories classified by socio-demographic and economic factors. The first level was 368,201 women aged 50-72 invited to the 2013-2014 screening campaign in metropolitan France. They were nested in 41 départements, the level of organisation of the FNOBCSP. The effect of travel time showed two main patterns: it was either linear (with participation decreasing as travel time increased) or participation first increased with increasing travel time to a peak around 5-15 min and decreased afterward. In nearly all types and départements, the probability of participation decreased linearly with increasing deprivation. Territorial inequities in participation were more context-dependent and complex than social inequities. Inequities in participation represent a loss of opportunity for individuals who already have the worst cancer outcomes. Evidence-based public health policies are needed to increase the effectiveness and equity of breast cancer screening.

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Introduction: Menopause is a vital stage in which the risk of the appearance of metabolic syndrome and cardiovascular diseases is increased. Cardiovascular risk in menopausal women must be monitored because it is one of the most common causes of mortality in these women. Smoking is an important risk factor for the development of many diseases, including cardiovascular diseases, so promoting smoking cessation in these women is important for the maintenance of cardiovascular health. Material and methods: Current smoking cessation programs mainly include nicotine and varenicline as therapeutic agents, due to their history of success, safety, and efficacy in aiding in cessation, but they do not include "new" agents such as cytisine as coadjuvant in the elimination of the habit of smoking. Results: Cytisine is a therapeutic agent traditionally used in Eastern Europe, which has demonstrated efficacy and safety in smoking cessation, also showing other new pharmacological actions. It has been widely used since World War II as a nicotine substitute. Conclusions: These pharmacological actions, together with their efficacy in smoking cessation, should be explored to evaluate the convenience of the use of cytisine in premenopausal and postmenopausal women, so that cytisine can be identified as a useful therapeutic tool in smoking cessation programs and in particular in menopausal women.

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Transport of K+ to the xylem is a key process in the mineral nutrition of the shoots. Although CIPK-CBL complexes have been widely shown to regulate K+ uptake transport systems, no information is available about the xylem ones. Here, we studied the physiological roles of the voltage-gated K+ channel SlSKOR and its regulation by the SlCIPK23-SlCBL1/9 complexes in tomato plants. We phenotyped gene-edited slskor and slcipk23 tomato knockout mutants and carried out two-electrode voltage-clamp (TEVC) and BiFC assays in Xenopus oocytes as key approaches. SlSKOR was preferentially expressed in the root stele and was important not only for K+ transport to shoots but also, indirectly, for that of Ca2+ , Mg2+ , Na+ , NO3 - , and Cl- . Surprisingly, the SlCIPK23-SlCBL1/9 complexes turned out to be negative regulators of SlSKOR. Inhibition of SlSKOR by SlCIPK23-SlCBL1/9 was observed in Xenopus oocytes and tomato plants. Regulation of SKOR-like channels by CIPK23-CBL1 complexes was also present in Medicago, grapevine, and lettuce but not in Arabidopsis and saltwater cress. Our results provide a molecular framework for coordinating root K+ uptake and its translocation to the shoot by SlCIPK23-SlCBL1/9 in tomato plants. Moreover, they evidenced that CIPK-CBL-target networks have evolved differently in land plants.

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