Analysis of the human Y-chromosome haplogroup Q characterizes ancient population movements in Eurasia and the Americas

Background: Recent genome studies of modern and ancient samples have proposed that Native Americans derive from a subset of the Eurasian gene pool carried to America by an ancestral Beringian population, from which two well-differentiated components originated and subsequently mixed in different proportion during their spread in the Americas. To assess the timing, places of origin and extent of admixture between these components, we performed an analysis of the Y-chromosome haplogroup Q, which is the only Pan-American haplogroup and accounts for virtually all Native American Y chromosomes in Mesoamerica and South America. Results: Our analyses of 1.5 Mb of 152 Y chromosomes, 34 re-sequenced in this work, support a "coastal and inland routes scenario" for the first entrance of modern humans in North America. We show a major phase of male population growth in the Americas after 15 thousand years ago (kya), followed by a period of constant population size from 8 to 3 kya, after which a secondary sign of growth was registered. The estimated dates of the first expansion in Mesoamerica and the Isthmo-Colombian Area, mainly revealed by haplogroup Q-Z780, suggest an entrance in South America prior to 15 kya. During the global constant population size phase, local South American hints of growth were registered by different Q-M848 sub-clades. These expansion events, which started during the Holocene with the improvement of climatic conditions, can be ascribed to multiple cultural changes rather than a steady population growth and a single cohesive culture diffusion as it occurred in Europe. Conclusions: We established and dated a detailed haplogroup Q phylogeny that provides new insights into the geographic distribution of its Eurasian and American branches in modern and ancient samples

Patients' and physicians' preferences for type 2 diabetes mellitus treatments in Spain and Portugal: a discrete choice experiment

Objective To assess Spanish and Portuguese patients’ and physicians’ preferences regarding type 2 diabetes mellitus (T2DM) treatments and the monthly willingness to pay (WTP) to gain benefits or avoid side effects. Methods An observational, multicenter, exploratory study focused on routine clinical practice in Spain and Portugal. Physicians were recruited from multiple hospitals and outpatient clinics, while patients were recruited from eleven centers operating in the public health care system in different autonomous communities in Spain and Portugal. Preferences were measured via a discrete choice experiment by rating multiple T2DM medication attributes. Data were analyzed using the conditional logit model. Results Three-hundred and thirty (n=330) patients (49.7% female; mean age 62.4 [SD: 10.3] years, mean T2DM duration 13.9 [8.2] years, mean body mass index 32.5 [6.8] kg/m2, 41.8% received oral + injected medication, 40.3% received oral, and 17.6% injected treatments) and 221 physicians from Spain and Portugal (62% female; mean age 41.9 [SD: 10.5] years, 33.5% endocrinologists, 66.5% primary-care doctors) participated. Patients valued avoiding a gain in bodyweight of 3 kg/6 months (WTP: €68.14 [95% confidence interval: 54.55–85.08]) the most, followed by avoiding one hypoglycemic event/month (WTP: €54.80 [23.29–82.26]). Physicians valued avoiding one hypoglycemia/week (WTP: €287.18 [95% confidence interval: 160.31–1,387.21]) the most, followed by avoiding a 3 kg/6 months gain in bodyweight and decreasing cardiovascular risk (WTP: €166.87 [88.63–843.09] and €154.30 [98.13–434.19], respectively). Physicians and patients were willing to pay €125.92 (73.30–622.75) and €24.28 (18.41–30.31), respectively, to avoid a 1% increase in glycated hemoglobin, and €143.30 (73.39–543.62) and €42.74 (23.89–61.77) to avoid nausea. Conclusion Both patients and physicians in Spain and Portugal are willing to pay for the health benefits associated with improved diabetes treatment, the most important being to avoid hypoglycemia and gaining weight. Decreased cardiovascular risk and weight reduction became the third most valued attributes for physicians and patients, respectively

Decrypting the Mitochondrial Gene Pool of Modern Panamanians

The Isthmus of Panama–the narrow neck of land connecting the northern and southern American landmasses–was an obligatory corridor for the Paleo-Indians as they moved into South America. Archaeological evidence suggests an unbroken link between modern natives and their Paleo-Indian ancestors in some areas of Panama, even if the surviving indigenous groups account for only 12.3% of the total population. To evaluate if modern Panamanians have retained a larger fraction of the native pre-Columbian gene pool in their maternally-inherited mitochondrial genome, DNA samples and historical records were collected from more than 1500 volunteer participants living in the nine provinces and four indigenous territories of the Republic. Due to recent gene-flow, we detected ∼14% African mitochondrial lineages, confirming the demographic impact of the Atlantic slave trade and subsequent African immigration into Panama from Caribbean islands, and a small European (∼2%) component, indicating only a minor influence of colonialism on the maternal side. The majority (∼83%) of Panamanian mtDNAs clustered into native pan-American lineages, mostly represented by haplogroup A2 (51%). These findings reveal an overwhelming native maternal legacy in today's Panama, which is in contrast with the overall concept of personal identity shared by many Panamanians. Moreover, the A2 sub-clades A2ad and A2af (with the previously named 6 bp Huetar deletion), when analyzed at the maximum level of resolution (26 entire mitochondrial genomes), confirm the major role of the Pacific coastal path in the peopling of North, Central and South America, and testify to the antiquity of native mitochondrial genomes in Panama

Preferencias de pacientes y médicos por los tratamientos de la diabetes mellitus tipo 2 en España y Portugal: disponibilidad a pagar por obtener beneficios adicionales y evitar efectos secundarios

El objetivo de este estudio es el evaluar las preferencias de los pacientes y médicos por los tratamientos para la diabetes mellitus tipo 2 (DM2) y la disponibilidad a pagar (DAP) por obtener beneficios adicionales o evitar efectos adversos, en España y Portugal. Para la consecución de este objetivo se llevó a cabo un estudio observacional, multicéntrico, exploratorio, enfocado en la práctica clínica habitual en España y Portugal. Los pacientes fueron reclutados en 11 centros hospitalarios y de atención primaria que operaban en el ámbito de la sanidad pública en diferentes Comunidades Autónomas en España y regiones de salud en Portugal, mientras que los médicos fueron reclutados de múltiples hospitales y clínicas ambulatorias ubicadas en diferentes regiones de España y Portugal. Las preferencias de los pacientes y médicos fueron medidas mediante un Experimento de Elección Discreta (EED) el cual incluía múltiples atributos de los medicamentos para la DM2. Los datos fueron analizados mediante un modelo Conditional Logit (C-Logit). Participaron 330 pacientes [49,7 % mujeres; edad media de 62,4 (DE: 10,1); con una media de 13,9 (DE: 8,2) años desde el diagnóstico de la DM2; índice de masa corporal (IMC) medio de 32,5 (DE: 6,8); 41,8 % recibían medicamentos orales en combinación con tratamientos inyectables, 40,3 % recibían tratamientos orales y 17,6 % tratamientos inyectables] y 221 médicos de España y Portugal [62 % mujeres; edad media de 41,9 (DE: 10,5) años; 33,5 % endocrinólogos, 65,5 % médicos de atención primaria]. El análisis de preferencias de los pacientes demostró que con excepción del nivel un evento hipoglucémico al mes, todos los niveles de atributos valorados fueron predictores significativos de la elección de los pacientes (p<0,05). Evitar ganar 3 kg en 6 meses fue el atributo más valorado, seguido por evitar un evento hipoglucémico al mes. El análisis de DAP demostró que los pacientes estaban dispuestos a pagar hasta 68,14€ (IC95%: 54,55€ – 85,08€)] por evitar ganar 3 kg en 6 meses y 54,80€ (IC95%: 23,39€ – 82,26€)] por evitar una hipoglucemia al mes. El análisis de preferencias de los médicos demostró que con excepción de los niveles un evento hipoglucémico al mes y reducción de 3 kg de peso en 6 meses, todos los niveles evaluados fueron predictores de las preferencias de los médicos (p<0,05). Evitar un evento hipoglucémico a la semana fue el nivel de atributos más preferido seguido de evitar ganar 3 kg en 6 meses y disminuir el riesgo cardiovascular. Los médicos estaban dispuestos a pagar 287,18€ (IC95%: 160,31€ – 1.387,21€)] por evitar un evento hipoglucémico a la semana, seguido por evitar un aumento de peso de 3 kg en 6 meses [DAP: 166,87€ (IC95%: 88,63€ – 843,09€)] y por la disminución del riesgo cardiovascular [DAP: 154,30€ (IC95%: 98,13€ – 434,19€)]. Los pacientes y médicos estaban dispuestos a pagar 24,28€ (IC95%: 18,41€ – 30,31€) y 125,92€ (IC95%: 73,30€ – 622,75€), respectivamente, por evitar un aumento del 1 % en el nivel de la hemoglobina glicosilada (HBA1c) y 42,74€ (IC95%: 23,89€ – 61,77€) y 143,30€ (IC95%: 73,39€ – 543,63€) por evitar las náuseas. Tanto los pacientes como los médicos en España y Portugal prefieren un tratamiento hipoglucemiante similar: un medicamento inyectable que sea administrado una vez al día sin relación con las comidas, que requiera monitorización de la glucosa sanguínea tres veces por semana, que mantenga los niveles de la HbA1c entre 6 % y 7 %, que reduzca el peso en 6 kg en 6 meses, que disminuya el riesgo cardiovascular, que no produzca náuseas y que se asocie únicamente con un episodio de hipoglucemia anual. Los resultados de este estudio permiten concluir que de las características de los tratamientos hipoglucemiantes, los pacientes y médicos prefieren el evitar hipoglucemias y ganar peso. La reducción del peso y la disminución del riesgo cardiovascular y son el tercer atributo mejor valorado por los pacientes y médicos, respectivamente. Adicionalmente, tanto los pacientes como los médicos en España y Portugal están dispuestos a pagar por los beneficios en salud asociados con una mejora del tratamiento antidiabético

Frequency distribution (%) of major haplogroups in Panama.

<p>Frequency distribution (%) of major haplogroups in Panama.</p

Sources and haplogroup affiliation for the A2ad and A2af complete mtDNA sequences.

<p>Sources and haplogroup affiliation for the A2ad and A2af complete mtDNA sequences.</p

Spatial distribution of A2af and A2ad mtDNAs identified in general mixed populations.

<p>Exact values are listed in Table S3A.</p

Network of A2af control-region haplotypes from Panama subdivided according to their geographic origin.

<p>The mutations on the connecting branches refer to the (revised) Cambridge reference sequence (rCRS) <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0038337#pone.0038337-Andrews1" target="_blank">[52]</a>. Markers of different clusters are in colors. Mutations are transitions unless the base change is explicitly indicated. Insertions, deletions and heteroplasmic mutations were excluded, with the notable exception of the 106–111 6 bp deletion. The size of each circle is proportional to the haplotype frequency and geographical origins are indicated by different colors. Coalescence ages of A2af and A2af1 are also reported using the control-region mutation rate reported by Soares <i>et al. </i><a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0038337#pone.0038337-Soares2" target="_blank">[50]</a>.</p