Temporal stability and directional change in a color cline of a marine snail from NW Spain.

The evolution and maintenance of color clines is a classic topic of research in evolutionary ecology. However, studies analyzing the temporal dynamics of such clines are much less frequent, due to the difficulty of obtaining reliable data about past color distributions along environmental gradients. In this article, we describe a case of decades-long temporal stability and directional change in a color cline of the marine snail Littorina saxatilis along the coastal inlet of the Ría de Vigo (NW Spain). L. saxatilis from this area shows a clear color cline with 3 distinct areas from the innermost to the more wave-exposed localities of the Ría: the inner, protected localities show an abundance of fawn-like individuals; the intermediate localities show a high diversity of colors; and the outer, wave-exposed localities show populations with a high frequency of a black and lineated morph. We compare data from the 1970s and 2022 in the same localities, showing that the cline has kept relatively stable for at least over half a century, except for some directional change and local variability in the frequency of certain morphs. Multiple regression analyses and biodiversity measures are presented to provide clues into the selective pressures that might be involved in the maintenance of this color cline. Future research avenues to properly test the explanatory power of these selective agents as well as the possible origins of the cline are discussed.

Precision medicine: "Point of Care Ultrasound" (PoCUS) in the diagnostic approach to the patient with hyponatremia.

Hyponatremia is a multifactorial disorder defined as a decrease in plasma sodium concentration. Its differential diagnosis requires an adequate evaluation of the extracellular volume (ECV). However, ECV determination, simply based on the clinical history, vital signs, physical examination, and laboratory findings can leads to misdiagnosis and inappropriate treatment. The use of Point-of-Care Ultrasound (POCUS), through the combination of Lung Ultrasound (LUS), Venous Excess UltraSound (VExUS) and Focused Cardiac Ultrasound (FoCUS), allows a much more accurate holistic assessment of the patient's ECV status in combination with the other parameters.

Serum phosphate is associated with increased risk of bone fragility fractures in hemodialysis patients.

BACKGROUND: Bone fragility fractures are associated with high morbidity and mortality. This study analysed the association between the current biochemical parameters of CKD-MBD and bone fragility fractures in the COSMOS project. METHODS: COSMOS is a 3-year, multicentre, open cohort, prospective, observational study carried out in 6797 hemodialysis patients (227 centres from 20 European countries). The association of bone fragility fractures (outcome) with serum calcium, phosphate and PTH (exposure), was assessed using Standard Cox proportional hazards regression and Cox proportional hazards regression for recurrent events. Additional analyses were performed considering all-cause mortality as a competitive event for bone fragility fracture occurrence. Multivariable models were used in all strategies, with the fully adjusted model including a total of 24 variables. RESULTS: During a median follow-up of 24 months 252 (4%) patients experienced at least one bone fragility fracture (incident bone fragility fracture rate 28.5 per 1000 patient-years). In the fractured and non-fractured patients, the percentage of men was 43.7% and 61.4%, mean age 68.1 and 63.8 years and a haemodialysis vintage of 55.9 and 38.3 months respectively. Baseline serum phosphate > 6.1 mg/dL (reference value 4.3-6.1 mg/dL) was significantly associated with a higher bone fragility fracture risk in both regression models (HR: 1.53[95%CI: 1.10-2.13] and HR: 1.44[95%CI: 1.02-2.05]. The significant association persisted after competitive risk analysis (subHR: 1.42[95%CI: 1.02-1.98]) but the finding was not confirmed when serum phosphate was considered as a continuous variable. Baseline serum calcium showed no association with bone fragility fracture risk in any regression model. Baseline serum PTH > 800 pg/mL was significantly associated with a higher bone fragility fracture risk in both regression models, but the association disappeared after a competitive risk analysis. CONCLUSIONS: Hyperphosphatemia was independently and consistently associated with an increased bone fracture risk, suggesting serum phosphate could be a novel risk factor for bone fractures in hemodialysis patients.

Chronic Kidney Disease-Associated Pruritus and Quality of Life: Learning from Our Patients.

Chronic kidney disease-associated pruritus is itching directly related to kidney disease that cannot be explained by any other condition. Despite technological advances in the different aspects of dialysis sessions and the best treatment for chronic kidney disease patients, it is still a common problem in our patients. The many complex physiological mechanisms involved, the different hypotheses made over the years on the aetiology of the condition, and the great clinical variability may partially explain the limited knowledge about this problem and the difficulties in treating it. The presence of all these factors leads to the persistence of unpleasant symptoms, which must affect the disease burden and quality of life of kidney patients. Through the presentation of an illustrative clinical case, the aim of this review article is to highlight the need for adequate diagnosis and an improved approach to all aspects of chronic kidney disease-associated pruritus, in view of the heavy burden of the disease and the huge impact on the patient's quality of life.

The 'Phosphorus Week': involvement of Spanish nephrologists in the control of phosphorus blood levels.

BACKGROUND: The adequate control of phosphorus levels is a major concern for professionals involved in the care of patients with chronic kidney disease (CKD), since high phosphorus levels are directly related to an increase in mortality. OBJECTIVES: To know the perception and involvement of Spanish nephrologists on the control of phosphorus levels, the so-called 'Phosphorus Week' was organized (November 13-17, 2017). METHODS: All members of the Spanish Society of Nephrology were invited to participate in an online survey, which included questions on aspects related to phosphorus control in patients with advanced CKD (aCKD) (glomerular filtration rate <30 ml/min/1, 73 m2) and in the different modalities of renal replacement therapies [peritoneal dialysis (PD), hemodialysis (HD) and renal transplantation (KT)]. RESULTS: 72 data entries were obtained in the survey with an inclusion of 7463 patients. Of them, 35.4% were on HD, 34.8% were KT, 24.2% had aCKD and 5.5% were on PD. The serum phosphorus level target for the four groups of patients was 4.5 mg/dl, with minimal variations depending on the area of ​​the national territory. The patients with better control of phosphataemia were patients with KT (93.3% had phosphorus values ​​<4.5 mg/dl), followed by patients with aCKD (65.6% with phosphorus <4.5 mg/dl). Only 53.6% of the patients on HD and 39.4% of those on PD reached the phosphorus goal <4.5 mg/dl. The group of patients on dialysis was the one in whom phosphorus binders prescribed the most (73.5% and 75.6% in HD and PD, respectively), being less frequent in patients with patients with aCKD (39.9%) and only 4.5 % in KT. CONCLUSIONS: The objectives of the Spanish nephrologists are in line with those recommended by the national and international clinical guidelines; however, there is still a wide room for improvement to achieve these goals, especially in HD and PD patients.

Functional Status of Patients over 65 Years Old Intervened on for a Hip Fracture One Year after the Operation.

OBJECTIVES: Evaluation of the functional status one year after a hip fracture surgery and the influence of sarcopenia and other clinical factors at the time of admission. METHOD: Prospective observational study with 135 patients over 65 years of age. Functional status of basic (modified Katz) and instrumental activities (Lawton and Brody) and walking ability (Functional Ambulation Classification, FAC) was measured on admission, at discharge, and telephonically one year later. The risk or positive screening of sarcopenia (SARC-F) and cognitive status (Pfeiffer), as well as clinical variables, were evaluated. RESULTS: 72% of patients are women; 36% have a risk of sarcopenia (Sarc-F ≥ 4), and 43% have moderate-severe cognitive impairment (Pfeiffer ≥ 5). Walking capacity at one year was closer to the values at admission more often in women than in men (0.2 ± 1.3 points vs. 0.9 ± 1.6; p = 0.001), as well as in patients without risk of sarcopenia versus sarcopenic patients (0.3 ± 1.2 points vs. 0.7 ± 1.7; p = 0.001), although their evolution did not show significant differences (p = 0.183). Instrumental activities after one year have not been recovered (1.7 ± 2.5 points; p = 0.032), and patients at risk of sarcopenia showed worse values (1.7 ± 1.9 points vs. 3.7 ± 2.7; p < 0.001) and worse evolution (p = 0.012). The evolution of basic activities varied according to the risk of sarcopenia (0.6 ± 1.4 points vs. 1.4 ± 2.1; p = 0.008). CONCLUSIONS: Functional status at one year is related to the functional status at admission, the positive screening of sarcopenia, sex, and cognitive impairment of the patient. Knowing at the time of admission an estimate of the functional status at one year will help to reinforce the individual treatment of patients with a worse prognosis.

Etiopathogenesis of chronic kidney disease-associated pruritus: putting the pieces of the puzzle together.

Defined as the unpleasant sensation that causes the desire to scratch, pruritus is the most common skin symptom associated with uremia and appears in almost half of patients with advanced chronic kidney disease (CKD). Beyond its direct impact on quality of life, CKD-associated pruritus (CKD-aP) is an independent predictor of mortality that also has a synergistic effect with other quality of life-related symptoms, such as insomnia, depression, and anxiety. Although different mechanisms have been proposed to explain the origin of Pa-ERC, its etiopathogenesis is still not fully understood. Since new therapeutic targets have been identified and several clinical trials have recently shown promising results, our current understanding of the interrelationships has expanded significantly and the pathophysiological mechanisms underlying CKD-aP are now considered to be multifactorial. The potential triggers of pruritus in patients with CKD are discussed in this review, including hypotheses about skin xerosis, accumulation of uremic toxins, dysregulation of the immune system and systemic inflammation, uremic neuropathy, and imbalances in the endogenous opioid system. Other non-uremic causes of pruritus are also discussed, with the aim of guiding the physicians to apply an adequate aetiopathogenic approach to CKD-aP in their day-to-day clinical practice.

Perception of Spanish nephrologists on an old unsolved problem: Pruritus associated with chronic kidney disease (CKD-aP).

INTRODUCTION: Pruritus associated with chronic kidney disease is defined as the sensation of itching, in people with chronic kidney disease, in a one area or all over the body that causes the need to scratch, after having ruled out other dermatological or systemic causes. It is an old and known problem whose prevalence has been able to decrease with the improvement of dialytic techniques but which still persists and is underdiagnosed. OBJECTIVES: The objective of this study was to analyse the current perception of nephrologists about this problem that influences the quality of life of people with chronic kidney disease through a survey. RESULTS: 135 nephrologists, most of them engaged in haemodialysis, participated. 86% considered that pruritus associated with chronic kidney disease is still a problem today that affects the quality of life. Most nephrologists believe that the main pathophysiological cause is uremic toxins (60%) and only 16% believe that it is due to the dysregulation of the opioid system/endorphins-dynorphins. Only 16% comment that the prevalence of pruritus in their centre is greater than 20%. 40% believe that the diagnosis is made because it is manifested by the patient and only 27% because it is asked by the doctor. Moreover, it is not usual to use scales to measure it or the codification in the medical records. The main treatment used is antihistamines (96%), followed by moisturizers/anaesthetics (93%) and modification of the dialysis regimen (70%). CONCLUSIONS: Pruritus associated with chronic kidney disease is still a current problem, it is underdiagnosed, not codified and with a lack of indicated, effective and safe treatments. Nephrologists do not know its real prevalence and the different pathophysiological mechanisms involved in its development. Many therapeutic options are used with very variable results, ignoring their efficacy and applicability at the present time. The new emerging kappa-opioid-receptor agonist agents offer us an opportunity to reevaluate this age-old problem and improve the quality of life for our patients with chronic kidney disease.

Shell color polymorphism in marine gastropods.

Marine gastropods are characterized by an incredible variation in shell color. In this review, we aim to introduce researchers to previous studies of shell color polymorphism in this group of animals, trying to provide an overview of the topic and highlighting some potential avenues for future research. For this, we tackle the different aspects of shell color polymorphism in marine gastropods: its biochemical and genetic basis, its patterns of spatial and temporal distribution, as well as its potential evolutionary causes. In particular, we put special emphasis on the evolutionary studies that have been conducted so far to reveal the evolutionary mechanisms responsible for the maintenance of shell color polymorphism in this group of animals, as it constitutes the least addressed aspect in existing literature reviews. Several general conclusions can be drawn from our review: First, natural selection is commonly involved in the maintenance of gastropod color polymorphism; second, although the contribution of neutral forces (gene flow-genetic drift equilibrium) to shell color polymorphism maintenance do not seem to be particularly important, it has rarely been studied systematically; third, a relationship between shell color polymorphism and mode of larval development (related to dispersal capability) may exist. As for future studies, we suggest that a combination of both classical laboratory crossing experiments and -Omics approaches may yield interesting results on the molecular basis of color polymorphism. We believe that understanding the various causes of shell color polymorphism in marine gastropods is of great importance not only to understand how biodiversity works, but also for protecting such biodiversity, as knowledge of its evolutionary causes may help implement conservation measures in those species or ecosystems that are threatened.

[Knowledge, use and opinion about written informed consent in primary healthcare nurses: CONOSER pilot project]. / Conocimiento, implementación y opinión acerca del consentimiento informado por escrito de las enfermeras de atención primaria: proyecto piloto CONOSER.

OBJECTIVE: To know the knowledge, implementation and opinion on informed consent of generalist nurses, specialists and primary care residents. DESIGN: Descriptive cross-sectional study using an online self-administered 'ad hoc' questionnaire. SETTING: Primary care nurses in Madrid, from November 2020 to March 2021. PARTICIPANTS: Sample of 114 nurses: 91 generalist, 20 specialists and 3 residents. MAIN MEASUREMENTS: Sociodemographics, knowledge, implementation and opinion. RESULTS: The response rate was 27.7%. As a general rule, 48.2% indicated that informed consent was collected verbally, as established by law, with differences being found between categories, this percentage being higher in specialists and residents (P=0.004), and within specialists in those who had obtained their speciality by internal resident nurse (IRN) (P<0.0001). In addition, specialists and residents were those who most identified the legal norm regulating informed consent (P<0.0001). In terms of implementation and opinion, all groups obtained similar results. DISCUSSION: There are no previous studies that have analysed these aspects of informed consent comparing the different categories. Studies from other healthcare and geographical areas show that nurses have greater knowledge, although the demand for specific training in bioethics and biolaw is greater in the nurses participating in this study. CONCLUSIONS: Nurses have adequate knowledge about informed consent, use it in clinical practice and have an appropriate conception of it, being higher in some items in specialist nurses IRN and in residents.

Thermodynamic effects drive countergradient responses in the thermal performance of Littorina saxatilis across latitude.

Thermal performance curves (TPCs) provide a powerful framework to assess the evolution of thermal sensitivity in populations exposed to divergent selection regimes across latitude. However, there is a lack of consensus regarding the extent to which physiological adjustments that compensate for latitudinal temperature variation (metabolic cold adaptation; MCA) may alter the shape of TPCs, including potential repercussion on upper thermal limits. To address this, we compared TPCs for cardiac activity in latitudinally-separated populations of the intertidal periwinkle Littorina saxatilis. We applied a non-linear TPC modelling approach to explore how different metrics governing the shape of TPCs varied systematically in response to local adaptation and thermal acclimation. Both critical upper limits, and the temperatures at which cardiac performance was maximised, were higher in the northernmost (cold-adapted) population and displayed a countergradient latitudinal trend which was most pronounced following acclimation to low temperatures. We interpret this response as a knock-on consequence of increased standard metabolic rate in high latitude populations, indicating that physiological compensation associated with MCA may indirectly influence variation in upper thermal limits across latitude. Our study highlights the danger of assuming that variation in any one aspect of the TPC is adaptive without appropriate mechanistic and ecological context.

Medicines in exceptional circumstances for solid tumours: focusing on evidence, effectiveness, and toxicity profiles.

OBJECTIVE: To analyse the applications for drugs in special situations (compassionate use, off-label use and foreign drugs) for solid  tumours, and to assess the level of evidence supporting these applications, as  well as the effectiveness and safety of most frequent drugs. METHOD: We performed a cross-sectional study of all applications for drugs in  special situations during 2018 and 2019 in a representative third-level centre.  We collected data about generic names of drugs, clinical indications, and level  of evidence provided on the application form. Furthermore, tumour response  was assessed according to the Response Evaluation Criteria in Solid Tumours  version 1.1., Progression Free Survival and Overall Survival. Safety was  evaluated with the National Cancer Institute Common Terminology Criteria for  Adverse Events, version 5.0. RESULTS: 2,273 drugs in special situations were approved between January  2018 and December 2019. In 431 cases (19%), they were used to treat solid  tumours. Out of 431, 291 (67.5%) applications were offlabel drugs, 76 (18%)  foreign drugs, and 64 (15%) were compassionate use of drugs. Most of them  were supported by phase 3 (47%) or phase 2 (33%)  clinical trials. The  majority of adverse effects were grade 1 and only in 6/67 cases the treatment  was discontinued due to toxicity. CONCLUSIONS: A significant number of drugs in special situations are prescribed  to Oncology patients. The majority of applications of these drugs was supported by clinical trials. The real-life experience showed an effectiveness and tolerance profile similar to those described in randomised  clinical trials.

OBJETIVO: Analizar las solicitudes de medicamentos en situaciones especiales (uso compasivo, uso fuera de indicación y medicamentos  extranjeros) para tumores sólidos, y evaluar el nivel de evidencia que avala  dichas solicitudes, así como la efectividad y seguridad de los medicamentos  más frecuentes.Método: Estudio transversal que incluyó las solicitudes de medicamentos en  situaciones especiales durante el período 2018-2019 en un centro representativo español de tercer nivel. Se recogieron datos sobre  principios activos, indicaciones clínicas y nivel de evidencia aportado en la  solicitud. Asimismo, la respuesta tumoral fue evaluada mediante criterios  Response Evaluation Criteria in Solid Tumours versión 1.1, supervivencia libre  de progresión y supervivencia global. La seguridad fue evaluada con la versión 5.0 de los criterios de toxicidad Common Terminology Criteria for  Adverse Events del National Cancer Institute de Estados Unidos. RESULTADOS: Un total de 2.273 medicamentos en situaciones especiales fueron aprobados entre enero de 2018 y diciembre de 2019. El 19% (431) se  aprobaron para el tratamiento de tumores sólidos. De estos 431, 291 (67,5%)  solicitudes fueron de medicamentos fuera de indicación, 76 (18%) extranjeros  y 64 (15%) en uso compasivo. La mayoría son avaladas por estudios clínicos  aleatorizados en fase III (47%) o fase II (33%). La mayor parte de los efectos  adversos fueron de grado 1 y solo en 6/67 casos el tratamiento fue  interrumpido por toxicidad. CONCLUSIONES: Un porcentaje importante de medicamentos en usos especiales se prescriben a pacientes oncológicos. La mayoría de las solicitudes fueron  avaladas por algún estudio clínico aleatorizado. La experiencia en vida real  mostró un perfil de efectividad y tolerancia similar al descrito en los estudios  clínicos aleatorizados.

Evolving spectrum but persistent high mortality of COVID-19 among patients on kidney replacement therapy in the vaccine era: the Spanish COVID-19 KRT Registry.

Background: Kidney replacement therapy (KRT) conferred a high risk for coronavirus disease 2019 (COVID-19) related mortality early in the pandemic. We evaluate the presentation, treatment and outcomes of COVID-19 in patients on KRT over time during the pandemic. Methods: This registry-based study involved 6080 dialysis and kidney transplant (KT) patients with COVID-19, representing roughly 10% of total Spanish KRT patients. Epidemiology, comorbidity, infection, vaccine status and treatment data were recorded, and predictors of hospital admission, intensive care unit (ICU) admission and mortality were evaluated. Results: Vaccine introduction decreased the number of COVID-19 cases from 1747 to 280 per wave. Of 3856 (64%) COVID-19 KRT patients admitted to the hospital, 1481/3856 (38%) were admitted during the first of six waves. Independent predictors for admission included KT and the first wave. During follow-up, 1207 patients (21%) died, 500/1207 (41%) during the first wave. Among vaccinated patients, mortality was 19%, mostly affecting KT recipients. Overall, independent predictors for mortality were older age, disease severity (lymphopaenia, pneumonia) and ICU rejection. Among patient factors, older age, male sex, diabetes, KT and no angiotensin receptor blockers (ARB) were independent predictors of death. In KT recipients, individual immunosuppressants were independent predictors of death. Over time, patient characteristics evolved and in later pandemic waves, COVID-19 was mainly diagnosed in vaccinated KT recipients; in the few unvaccinated dialysis patients, ICU admissions increased and mortality decreased (28% for the first wave and 16-22% thereafter). Conclusions: The clinical presentation and outcomes of COVID-19 during the first wave no longer represent COVID-19 in KRT patients, as the pandemic has become centred around vaccinated KT recipients. Vaccines lowered the incidence of diagnosed COVID-19 and mortality. However, mortality remains high despite increased access to ICU care.

Recommendations for the management of hyperkalemia in the emergency department. / Recomendaciones para el manejo de la hiperpotasemia en urgencias.

TEXT: Hyperkalemia, a common electrolyte disorder, is seen often in emergency departments. Patient outcomes are impacted by proper management, which requires consideration of both clinical and laboratory findings in relation to kidney function, hydration, the acid-base balance, and heart involvement. Delicate decisions about the timing of potassium level correction must be tailored in each case. For these reasons the Spanish Society of Emergency Medicine (SEMES), the Spanish Society of Cardiology (SEC), and the Spanish Society of Nephrology (SEN) joined forces to come to a consensus on defining the problem and recommending treatments that improve hospital emergency department management of hyperkalemia. Intravenous calcium, insulin and glucose, and salbutamol continue to be used to treat acute hyperkalemia. Either loop or thiazide diuretics can help patients if volume is not depleted, and dialysis may be necessary if there is kidney failure. Ion-exchange resins are falling into disuse because of adverse effects and poor tolerance, whereas novel gastrointestinal cation-exchange resins are gaining ground and may even be of some use in managing acute cases. It is essential to adjust treatment rather than discontinue medications that, even if they favor the development of hyperkalemia, will improve a patient's long-term prognosis. Valid alternative treatment approaches must therefore be sought for each patient group, and close follow-up is imperative.

TEXTO: La hiperpotasemia es un trastorno electrolítico frecuente en los servicios de urgencias y un manejo adecuado impacta en el pronóstico de los pacientes. Este requiere de la integración de datos clínicos y analíticos sobre el estado de la función renal, la hidratación, el equilibrio ácido-base y la afectación cardiaca. Además, es necesaria una precisa toma de decisiones sobre la corrección de la concentración de potasio en el tiempo indicado para cada caso. Por estos motivos la SEMES (Sociedad Española de Medicina de Urgencias y Emergencias), la SEC (Sociedad Española de Cardiología) y la SEN (Sociedad Española de Nefrología) unen esfuerzos en consensuar definiciones y tratamientos que podrían mejorar el abordaje de estos pacientes en los servicios de urgencias hospitalarios. El calcio intravenoso, la insulina con glucosa y el salbutamol siguen siendo los tratamientos que se emplean en la hiperpotasemia aguda. Los diuréticos de asa y tiazídicos también pueden ayudar en pacientes no depleccionados, y la hemodiálisis puede ser necesaria en hiperpotasemias graves en el contexto de insuficiencia renal. Los efectos secundarios y la baja tolerabilidad de las resinas de intercambio iónico están haciendo que caigan en desuso mientras que los nuevos intercambiadores catiónicos gastrointestinales van ganando su espacio e incluso podrían tener algún valor en el tratamiento agudo. Es fundamental el ajuste del tratamiento evitando retirar fármacos que, a pesar de favorecer la hiperpotasemia, mejoren el pronóstico a largo plazo, por lo que es imperativo buscar alternativas válidas para cada grupo de pacientes, asegurando después un estrecho seguimiento.

Proteomic analysis of F1 hybrids and intermediate variants in a Littorina saxatilis hybrid zone.

Proteomic analysis was carried out on the Crab (upper-shore) and Wave (lower-shore) ecotypes of Littorina saxatilis from a hybrid zone at Silleiro Cape, Spain. Proteome profiles of individual snails were obtained. Protein expression in F1 hybrid snails bred in the laboratory and snails with intermediate shell phenotypes collected from the mid-shore were compared with Crab and Wave ecotypes using analytical approaches used to study dominance. Multivariate analysis over many protein spots showed that the F1 snails are distinct from both ecotypes but closer to the Wave ecotype. The intermediate snails are highly variable, some closer to the Crab and others to the Wave ecotype. Considered on a protein by protein basis, some proteins are significantly closer in expression to the Crab and others to the Wave ecotype for both F1 and intermediate snails. Furthermore, a significant majority of proteins were closer in expression to the Wave ecotype for the F1, consistent with the multivariate analysis. No such significant majority toward either the Crab or Wave ecotype was observed for the intermediate snails. The closer similarity of F1 and Wave ecotype expression patterns could be the result of similar selective pressures in the similar mid-shore and low-shore environments. For a significantly larger number of proteins, intermediate snails were closer in expression to the ecotype having the lower expression, for both Crab and Wave ecotypes. This is somewhat unexpected as lower expression might be expected to be an indication of impairment of function and lower fitness. Proteomic analysis could be important for the identification of candidate proteins useful for gaining improved understanding of adaptation and barriers to gene flow in hybrid zones.