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Land cover responses to climate change must be quantified for understanding Arctic climate, managing Arctic water resources, maintaining the health and livelihoods of Arctic societies and for sustainable economic development. This need is especially pressing in Greenland, where climate changes are amongst the most pronounced of anywhere in the Arctic. Ice loss from the Greenland Ice Sheet and from glaciers and ice caps has increased since the 1980s and consequently the proglacial parts of Greenland have expanded rapidly. Here we determine proglacial land cover changes at 30 m spatial resolution across Greenland during the last three decades. Besides the vastly decreased ice cover (- 28,707 km2 ± 9767 km2), we find a doubling in total areal coverage of vegetation (111% ± 13%), a quadrupling in wetlands coverage (380% ± 29%), increased meltwater (15% ± 15%), decreased bare bedrock (- 16% ± 4%) and increased coverage of fine unconsolidated sediment (4% ± 13%). We identify that land cover change is strongly associated with the difference in the number of positive degree days, especially above 6 °C between the 1980s and the present day. Contrastingly, absolute temperature increase has a negligible association with land cover change. We explain that these land cover changes represent local rapid and intense geomorphological activity that has profound consequences for land surface albedo, greenhouse gas emissions, landscape stability and sediment delivery, and biogeochemical processes.
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Favipiravir is a ribonucleoside analogue that has been explored as a therapeutic for the treatment of Ebola Virus Disease (EVD). Promising data from rodent models has informed nonhuman primate trials, as well as evaluation in patients during the 2013-2016 West African EVD outbreak of favipiravir treatment. However, mixed results from these studies hindered regulatory approval of favipiravir for the indication of EVD. This study examined the influence of route of administration, duration of treatment, and treatment schedule of favipiravir in immune competent mouse and guinea pig models using rodent-adapted Zaire ebolavirus (EBOV). A dose of 300 mg/kg/day of favipiravir with an 8-day treatment was found to be fully effective at preventing lethal EVD-like disease in BALB/c mice regardless of route of administration (oral, intraperitoneal, or subcutaneous) or whether it was provided as a once-daily dose or a twice-daily split dose. Preclinical data generated in guinea pigs demonstrates that an 8-day treatment of 300 mg/kg/day of favipiravir reduces mortality following EBOV challenge regardless of route of treatment or duration of treatments for 8, 11, or 15 days. This work supports the future translational development of favipiravir as an EVD therapeutic.
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Amidas , Antivirales , Modelos Animales de Enfermedad , Ebolavirus , Fiebre Hemorrágica Ebola , Ratones Endogámicos BALB C , Pirazinas , Animales , Amidas/uso terapéutico , Amidas/administración & dosificación , Amidas/farmacología , Cobayas , Pirazinas/administración & dosificación , Pirazinas/uso terapéutico , Fiebre Hemorrágica Ebola/tratamiento farmacológico , Ratones , Ebolavirus/efectos de los fármacos , Antivirales/administración & dosificación , Antivirales/uso terapéutico , Femenino , Vías de Administración de Medicamentos , Esquema de MedicaciónRESUMEN
Understanding the strain dynamic behavior of catalysts is crucial for the development of cost-effective, efficient, stable, and long-lasting catalysts. Using time-resolved Bragg coherent diffraction imaging at the fourth generation Extremely Brilliant Source of the European Synchrotron (ESRF-EBS), we achieved subsecond time resolution during operando chemical reactions. Upon investigation of Pt nanoparticles during CO oxidation, the three-dimensional strain profile highlights significant changes in the surface and subsurface regions, where localized strain is probed along the [111] direction. Notably, a rapid increase in tensile strain was observed at the top and bottom Pt {111} facets during CO adsorption. Moreover, we detected oscillatory strain changes (6.4 s period) linked to CO adsorption during oxidation, where a time resolution of 0.25 s was achieved. This approach allows for the study of adsorption dynamics of catalytic nanomaterials at the single-particle level under operando conditions, which provides insight into nanoscale catalytic mechanisms.
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Molnupiravir (EIDD-2801) is a prodrug of a ribonucleoside analogue that is currently being used under a US FDA emergency use authorization for the treatment of mild to moderate COVID-19. We evaluated molnupiravir for efficacy as an oral treatment in the rhesus macaque model of SARS-CoV-2 infection. Twenty non-human primates (NHPs) were challenged with SARS-CoV-2 and treated with 75 mg/kg (n = 8) or 250 mg/kg (n = 8) of molnupiravir twice daily by oral gavage for 7 days. The NHPs were observed for 14 days post-challenge and monitored for clinical signs of disease. After challenge, all groups showed a trend toward increased respiration rates. Treatment with molnupiravir significantly reduced viral RNA levels in bronchoalveolar lavage (BAL) samples at Days 7 and 10. Considering the mild to moderate nature of SARS-CoV-2 infection in the rhesus macaque model, this study highlights the importance of monitoring the viral load in the lung as an indicator of pharmaceutical efficacy for COVID-19 treatments. Additionally, this study provides evidence of the efficacy of molnupiravir which supplements the current ongoing clinical trials of this drug.
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COVID-19 , SARS-CoV-2 , Animales , Macaca mulatta , Citidina/farmacología , Citidina/uso terapéuticoRESUMEN
The CITIUS detector is a next-generation high-speed X-ray imaging detector. It has integrating-type pixels and is designed to show a consistent linear response at a frame rate of 17.4â kHz, which results in a saturation count rate of over 30â Mcpsâ pixel-1 when operating at an acquisition duty cycle close to 100%, and up to 20 times higher with special extended acquisition modes. Here, its application for Bragg coherent diffraction imaging is demonstrated by taking advantage of the fourth-generation Extremely Brilliant Source of the European Synchrotron (ESRF-EBS, Grenoble, France). The CITIUS detector outperformed a photon-counting detector, similar spatial resolution being achieved (20â ±â 6â nm versus 22â ±â 9â nm) with greatly reduced acquisition times (23â s versus 200â s). It is also shown how the CITIUS detector can be expected to perform during dynamic Bragg coherent diffraction imaging measurements. Finally, the current limitations of the CITIUS detector and further optimizations for coherent imaging techniques are discussed.
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BACKGROUND: Patients discharged to the home on home-based outpatient parenteral antimicrobial therapy (OPAT) perform their own infusions and catheter care; thus, they require high-quality training to improve safety and the likelihood of treatment success. This article describes the study team's experience piloting an educational toolkit for patients on home-based OPAT. METHODS: An OPAT toolkit was developed to address barriers such as unclear communication channels, rushed instruction, safe bathing with an intravenous (IV) catheter, and lack of standardized instructions. The research team evaluated the toolkit through interviews with home infusion nurses implementing the intervention, surveys of 20 patients who received the intervention, and five observations of the home infusion nurses delivering the intervention to patients and caregivers. RESULTS: Of surveyed patients, 90.0% were comfortable infusing medications at the time of discharge, and 80.0% with bathing with the IV catheter. While all practiced on equipment, 75.0% used the videos and the paper checklists. Almost all (95.0%) were satisfied with their training, and all were satisfied with managing their IV catheters at home. The videos were considered very helpful, particularly as reference. Overall, nurses adjusted training to patient characteristics and modified the toolkit over time. Shorter instruction forms were more helpful than longer instruction forms. CONCLUSION: Developing a toolkit to improve the education of patients on home-based OPAT has the potential to improve the safety of and experience with home-based OPAT.
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Antiinfecciosos , Pacientes Ambulatorios , Atención Ambulatoria , Antibacterianos , Humanos , Infusiones Parenterales , Alta del PacienteRESUMEN
Understanding the ultrashort time scale structural dynamics of the FeRh metamagnetic phase transition is a key element in developing a complete explanation of the mechanism driving the evolution from an antiferromagnetic to ferromagnetic state. Using an X-ray free electron laser we determine, with sub-ps time resolution, the time evolution of the (-101) lattice diffraction peak following excitation using a 35 fs laser pulse. The dynamics at higher laser fluence indicates the existence of a transient lattice state distinct from the high temperature ferromagnetic phase. By extracting the lattice temperature and comparing it with values obtained in a quasi-static diffraction measurement, we estimate the electron-phonon coupling in FeRh thin films as a function of laser excitation fluence. A model is presented which demonstrates that the transient state is paramagnetic and can be reached by a subset of the phonon bands. A complete description of the FeRh structural dynamics requires consideration of coupling strength variation across the phonon frequencies.
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PURPOSE: To identify barriers to safe and effective completion of outpatient parenteral antimicrobial therapy (OPAT) in patients discharged from an academic medical center and to develop targeted solutions to potentially resolve or improve the identified barriers. SUMMARY: A failure modes and effects analysis (FMEA) was conducted by a multidisciplinary OPAT task force to evaluate the processes for patients discharged on OPAT to 2 postdischarge dispositions: (1) home and (2) skilled nursing facility (SNF). The task force created 2 process maps and identified potential failure modes, or barriers, to the successful completion of each step. Thirteen and 10 barriers were identified in the home and SNF process maps, respectively. Task force members created 5 subgroups, each developing solutions for a group of related barriers. The 5 areas of focus included (1) the OPAT electronic order set, (2) critical tasks to be performed before patient discharge, (3) patient education, (4) patient follow-up and laboratory monitoring, and (5) SNF communication. Interventions involved working with information technology to update the electronic order set, bridging communication and ensuring completion of critical tasks by creating an inpatient electronic discharge checklist, developing patient education resources, planning a central OPAT outpatient database within the electronic medical record, and creating a pharmacist on-call pager for SNFs. CONCLUSION: The FMEA approach was helpful in identifying perceived barriers to successful transitions of care in patients discharged on OPAT and in developing targeted interventions. Healthcare organizations may reproduce this strategy when completing quality improvement planning for this high-risk process.
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Antiinfecciosos , Análisis de Modo y Efecto de Fallas en la Atención de la Salud , Cuidados Posteriores , Atención Ambulatoria , Antibacterianos/uso terapéutico , Antiinfecciosos/uso terapéutico , Humanos , Infusiones Parenterales , Pacientes Ambulatorios , Alta del PacienteRESUMEN
Rapid changes observed today in mountain glaciers need to be put into a longer-term context to understand global sea-level contributions, regional climate-glacier systems and local landscape evolution. In this study we determined volume changes for 400 mountain glaciers across the Southern Alps, New Zealand for three time periods; pre-industrial "Little Ice Age (LIA)" to 1978, 1978 to 2009 and 2009 to 2019. At least 60 km3 ± 12 km3 or between 41 and 62% of the LIA total ice volume has been lost. The rate of mass loss has nearly doubled from - 0.4 m w.e year-1 during 1,600 to 1978 to - 0.7 m w.e year-1 at present. In comparison Patagonia has lost just 11% of it's LIA volume. Glacier ice in the Southern Alps has become restricted to higher elevations and to large debris-covered ablation tongues terminating in lakes. The accelerating rate of ice loss reflects regional-specific climate conditions and suggests that peak glacial meltwater production is imminent if not already passed, which has profound implications for water resources and riverine habitats.
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Knowledge of the genetic landscape of aggressive well differentiated thyroid cancers (WDTC) is lacking. Retrospective review of institutional database was performed to identify locally-invasive thyroid carcinomas and a comparison cohort of low-risk WDTC. ThyroSeq v2 next-generation sequencing was performed on available tissue. Survival time was analyzed by Kaplan-Meier methods and compared between groups via the log-rank test. Time to recurrence, treating death as a competing risk, was analyzed by cumulative incidence and compared between groups. Of 80 T4 tumors, 29 (36%) were met inclusion criteria, of which, 25 had genetic and clinicopathologic data. Most (24/25, 96%) harbored at least one genetic alteration, most commonly BRAF V600E (19, 76%), followed by mutations in the promoter region of TERT (14, 56%). Co-occurrence of BRAF and TERT was identified in 12 (48%) and associated with significantly higher risk of recurrence (p < 0.05). Conversely, co-occurrence of BRAF and TERT was present in only 5 of 102 (5%) patients presenting with early-stage WDTC. Compared to early-stage WDTC, co-occurrence of BRAF and TERT mutations are common in locally advanced (T4) thyroid cancer and are associated with an increased risk of recurrence. This knowledge may help predict aggressive behavior pretreatment and inform perioperative decision-making.
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Biomarcadores de Tumor , Neoplasias de la Tiroides/genética , Neoplasias de la Tiroides/patología , Adulto , Anciano , Anciano de 80 o más Años , Progresión de la Enfermedad , Femenino , Perfilación de la Expresión Génica , Secuenciación de Nucleótidos de Alto Rendimiento , Humanos , Masculino , Persona de Mediana Edad , Mutación , Clasificación del Tumor , Metástasis de la Neoplasia , Estadificación de Neoplasias , RecurrenciaRESUMEN
Mandatory community-acquired pneumonia (CAP) protocol usage was proposed in our community-based teaching hospital because of senior medical staff perceptions that excessive variation in CAP care was adversely affecting clinical outcomes and costs. The purpose of our study was to examine CAP process of care variation, outcomes, and costs to ascertain whether the mandatory CAP protocol could be justified. The study consisted of an analysis of administrative and sampled chart data. We looked at pneumonia severity, orders for blood cultures or sputum staining, antibiotic usage, symptom resolution, length of stay, discharge status, readmission risk by follow-up time, and financial data. We found that process of care variation was low, clinical outcomes were generally good, and CAP care was profitable. Our data suggested that the proposed mandatory CAP protocol was not necessary. Our experience supports the management principle that fact finding should usually precede decision making, not the reverse.
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Atención al Paciente/economía , Neumonía Bacteriana/tratamiento farmacológico , Neumonía Bacteriana/economía , Garantía de la Calidad de Atención de Salud/métodos , Anciano , Antibacterianos/uso terapéutico , Infecciones Comunitarias Adquiridas/tratamiento farmacológico , Infecciones Comunitarias Adquiridas/economía , Vías Clínicas/normas , Femenino , Hospitales con más de 500 Camas , Costos de Hospital , Hospitales Comunitarios , Humanos , Tiempo de Internación , Masculino , Evaluación de Procesos y Resultados en Atención de Salud/métodos , Garantía de la Calidad de Atención de Salud/economíaRESUMEN
We demonstrate a low-temperature layer-by-layer formation of a metal-oxide-only (AlOx) gate dielectric to attain low-voltage operation of a self-assembly based vertical organic field effect transistor (VOFET). The AlOx deposition method results in uniform films characterized by high quality dielectric properties. Pin-hole free ultrathin layers with thicknesses ranging between 1.2 and 24 nm feature bulk dielectric permittivity, εAlOx, of 8.2, high breakdownfield (>8 MV cm(-1)), low leakage currents (<10(-7) A cm(-2) at 3MV cm(-1)), and high capacitance (up to 1 µF cm(-2)). We show the benefits of the tunable surface properties of the oxide-only dielectric utilized here, in facilitating the subsequent nanostructuring steps required to realize the VOFET patterned source electrode. Optimal wetting properties enable the directional block-copolymer based self-assembly patterning, as well as the formation of robust and continuous ultrathin metallic films. Supported by computer modeling, the vertical architecture and the methods demonstrated here offer a simple, low-cost, and free of expensive lithography route for the realization of low-voltage (VGS/DS≤3 V), low-power, and potentially high-frequency large-area electronics.
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This paper reports a precise, live cell-patterning method by means of patterning a silicon or glass substrate with alternating cytophilic and cytophobic self-assembled monolayers (SAMs) deposited via molecular vapor deposition. Specifically, a stack of hydrophobic heptadecafluoro-1,1,2,2-tetrahydrodecyltrichlorosilane SAMs and a silicon oxide adhesion layer were patterned on the substrate surface, and a hydrophilic SAM derived from 3-trimethoxysilyl propyldiethylenetriamine was coated on the remaining non-treated areas on the substrate surface to promote cell growth. The primary characteristics of the reported method include: (i) single-cell resolution; (ii) easy alignment of the patterns with the pre-existing patterns on the substrate; (iii) easy formation of nanoscale patterns (depending on the exposure equipment); (iv) long shelf life of the substrate pattern prior to cell culturing; (v) compatibility with conventional, inverted, optical microscopes for simple visualization of patterns formed on a glass wafer; and (vi) the ability to support patterned cell (osteoblast) networks for at least 2 weeks. Here, we describe the deposition technique and the characterization of the deposited layers, as well as the application of this method in the fabrication of multielectrode arrays supporting patterned neuronal networks.
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Osteoblastos/citología , Animales , Línea Celular Transformada , Ratones , Microscopía Electrónica de Rastreo , Microscopía FluorescenteRESUMEN
In rats, dietary protein intake influences brain concentrations of tryptophan, tyrosine, and other large neutral amino acids (LNAAs) and the neurotransmitters to which they are linked. Few experiments have examined these dietary protein-amino acid relationships in nonhuman primates, in relation to time of day or dietary protein content. We therefore examined the effect in monkeys of changes in chronic protein intake on 24-hour plasma and cerebrospinal fluid (CSF) concentrations of LNAAs (tyrosine, phenylalanine, branched-chain amino acids) and basic amino acids. Juvenile male monkeys (Macaca mulatta) consumed for sequential 4-week periods diets differing in protein content (approximately 23% --> approximately 16% --> approximately 10% --> approximately 6% protein [percentage of energy]). The daily ration was presented as a morning meal of fruit and an afternoon meal of fruit and a commercial diet to mimic feeding patterns in the wild. During week 4 on each diet, blood and CSF were sampled repeatedly over a 48-hour period via indwelling catheters. Plasma and CSF LNAA concentrations varied markedly with time of day and dietary protein content, showing up to 4-fold variations. Diurnal variations in plasma and CSF basic amino acids were smaller in magnitude and generally not strongly linked to dietary protein content. A measure of the competitive transport of LNAAs across the blood-brain barrier, calculated using plasma concentrations of the LNAAs and their blood-brain barrier kinetic constants, predicted the observed CSF concentration of each LNAA examined remarkably well, except for phenylalanine. Based on observations in rats, the variations in the CSF concentrations of the LNAAs in monkeys may be large enough to influence metabolic and signaling pathways in brain to which they have been linked.
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Aminoácidos Básicos/líquido cefalorraquídeo , Aminoácidos Neutros/líquido cefalorraquídeo , Encéfalo/metabolismo , Proteínas en la Dieta/administración & dosificación , Aminoácidos Básicos/sangre , Aminoácidos de Cadena Ramificada/sangre , Aminoácidos de Cadena Ramificada/líquido cefalorraquídeo , Aminoácidos Neutros/sangre , Animales , Barrera Hematoencefálica , Peso Corporal , Ritmo Circadiano , Ingestión de Alimentos , Macaca mulatta , MasculinoRESUMEN
Previous studies of postpartum amenorrhea (PPA) demonstrated distinct subgroups of women with short and long durations of amenorrhea. This phenomenon was attributed to cases where breastfeeding is absent because of pregnancy loss or infant death, or confusion of postpartum bleeding with resumption of menses. We explored these ideas using data from an 11-month prospective study in Bangladesh in which 858 women provided twice-weekly interviews and urine specimens for up to 9 months; 300 women were observed while experiencing PPA. The resulting exact, interval-censored, or right-censored durations were used to estimate parameters of two-component mixture models. A mixture of two Weibull distributions provided the best fit to the observations. The long-duration subgroup made up 84% (+/- 4% SE) of the population, with a mean duration of 457 (+/- 31) days. The short-duration subgroup had a mean duration of 94 (+/- 17) days. Three covariates were associated with the duration of PPA: women whose husbands had high-wage employment had a greater probability of falling in the short-duration subgroup; women in the long-duration subgroup whose husbands seasonally migrated had shorter periods of PPA within the subgroup; and mothers in the short-duration subgroup who gave birth during the monsoon season experienced a shortened duration of PPA within the subgroup. We conclude that the bimodal distribution of PPA reflects biological or behavioral heterogeneity rather than shortcomings of data collection.
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Amenorrea/epidemiología , Periodo Posparto/fisiología , Población Rural/estadística & datos numéricos , Adolescente , Adulto , Amenorrea/orina , Bangladesh/epidemiología , Estrona/análogos & derivados , Estrona/orina , Femenino , Humanos , Funciones de Verosimilitud , Persona de Mediana Edad , Periodo Posparto/orina , Pregnanodiol/análogos & derivados , Pregnanodiol/orina , Estudios Prospectivos , Distribuciones EstadísticasRESUMEN
Establishment of lactation has important biological and emotional health consequences for the newborn. Even so, substantial variation within a culture and among different cultures is seen in the onset of breastfeeding. Parametric mixture models are used to explore this variation and to uncover general human patterns for the initiation of breastfeeding. The model components reflect two hypothesized patterns of behavior. The first component is a "natural" pattern of breastfeeding that reflects, to some extent, a general mammalian behavior. The second component arises through culturally mediated behaviors that affect the initiation of breastfeeding. The model was fit by maximum likelihood to interval- and right-censored observations on 26220 mother-infant pairs collected from 25 previously published studies of breastfeeding behavior. Both model components were clearly statistically identified. Effects of cultural and geographic covariates were found to have significant effects on all components of the model. Although there is clear evidence for two distinct patterns of behavior in the initiation of breastfeeding, the results suggest that learned behaviors play an important role in mediating even "natural" breastfeeding behavior.
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Lactancia Materna/psicología , Lactancia Materna/estadística & datos numéricos , Modelos Psicológicos , Modelos Estadísticos , Comparación Transcultural , Femenino , Humanos , Conducta Materna , Relaciones Madre-Hijo , Factores de TiempoRESUMEN
Given the same reproductive span, more children with shorter interbirth intervals and less parental attention per child should not do as well. There should be intermediate optima in family sizes, but only two studies have demonstrated optima. The goal here is to determine whether the relationship between fitness and fertility is linear and whether this relationship masks underlying variation in reproductive behaviors in a Mennonite congregation that lived in two disease settings, Prussia/Russia vs. Kansas. The relationships between children born and fitness were determined by calculating linear and quadratic regressions for total, Prussia/Russia vs. Kansas, and families with deaths vs. families with no deaths for total, Prussia/Russia, and Kansas. Variation was examined in terms of measures of reproductive success and reproductive span. Comparisons were made by t tests with Bonferroni correction. Regressions demonstrate equally well that the more children women bear, the higher the reproductive success, whether in the harsher disease ecology of rural Prussia/Russia or in less challenging rural Kansas and whether the women experience deaths or not. Prussian/Russian mothers bore significantly more children (6.5+/-0.3) than Kansan mothers (5.6+/-0.2) over longer reproductive spans but did not significantly increase the number of surviving children (4.9+/-0.2 vs. 4.7+/-0.2, respectively). Families experiencing deaths vs. no deaths exhibit significantly longer reproductive spans, reflecting a significantly earlier start at childbearing and a later finish, and produce significantly more children (5.4+/-0.2 vs. 4.2+/-0.2). Cox regressions were run, and the most significant covariates to negatively affect survivorship to 15 years were death in the family and length of the previous interbirth intervals. There was variation in families, but perhaps most had adequate nutrition, which may explain the lack of optima in fitness.
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Tasa de Natalidad , Emigración e Inmigración/historia , Composición Familiar/etnología , Protestantismo/historia , Conducta Reproductiva/etnología , Conducta Reproductiva/historia , Adolescente , Adulto , Agricultura , Intervalo entre Nacimientos/etnología , Niño , Preescolar , Femenino , Fertilidad , Alemania/epidemiología , Historia del Siglo XIX , Historia del Siglo XX , Humanos , Lactante , Recién Nacido , Kansas/epidemiología , Esperanza de Vida , Masculino , Persona de Mediana Edad , Responsabilidad Parental , Paridad , Rusia (pre-1917)/epidemiología , Factores de TiempoRESUMEN
Hormonal changes that occur before or during parturition are known to trigger early postpartum maternal behaviors in many mammals. In humans, little evidence has been found for hormonal mediation of early postpartum maternal behavior. In this paper, we investigate associations between fetoplacental hormone concentrations in late pregnancy on the time from parturition to initiation of breast-feeding. A sample of 91 pregnant rural Bangladeshi women, enrolled in a 9-month prospective study, provided twice-weekly urine specimens and structured interviews. The subjects provided self-reports of time from parturition to initiation of breast-feeding. Specimens were assayed for urinary concentrations of human chorionic gonadotropin (hCG), pregnanediol-3alpha-glucuronide (PdG, a metabolite of progesterone), and urinary estrone conjugates (E1C). Parametric hazards analysis was used to investigate the effects of hCG, PdG, and E1C concentrations and other covariates (mother's age, parity, and child's sex) on the duration from parturition to breast-feeding. Mother's age, parity, the child's sex, hCG, and PdG showed no association with the onset of breast-feeding. Urinary E1C was significantly associated with time to initiation of breast-feeding, explaining about 4% of the variation in the behavior. The relationship was positive so that higher prepartum concentrations of EIC were associated with later times to initiation of breast-feeding. The direction of this relationship is opposite that found for many other species of mammals but is consistent with some recent findings in primates.