The burden of depression and anxiety disorders is greater in women, and female sex hormones have been shown to affect mood. Psychological side effects of hormonal contraception (HC) are also a common ...complaint in the clinic, but few previous studies have investigated this subject. We therefore wanted to investigate whether use of HC was associated with adverse psychological health outcomes, and whether this association was modified by age. All women aged 12-30 years on 31 December 2010, residing in Sweden for at least four years and with no previous psychiatric morbidity (n = 815 662), were included. We followed the women from their first HC use (or 31 December 2010, if they were non-users) at baseline, until a prescription fill of psychotropic drugs or the end of the one-year follow-up. We performed age-stratified logistic regression models and estimated odds ratios (OR) to measure the association between different HC methods and psychotropic drug use, as well as the area under the receiver operating curve to estimate discriminatory accuracy of HC in relation to psychotropic drugs. Overall, we found an association between HC and psychotropic drugs (adjusted OR 1.34, 95% confidence interval CI 1.30-1.37). In the age-stratified analysis, the strongest association was found in adolescent girls (adjusted OR 3.46, 95% CI 3.04-4.94 for age 12 to 14 years), while it was non-existent for adult women. We conclude that hormonal contraception is associated with psychotropic drug use among adolescent girls, suggesting an adverse effect of HC on psychological health in this population.
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A commercial polymeric film (Parafilm M®, a blend of a hydrocarbon wax and a polyolefin) was evaluated as a model membrane for microneedle (MN) insertion studies. Polymeric MN arrays ...were inserted into Parafilm M® (PF) and also into excised neonatal porcine skin. Parafilm M® was folded before the insertions to closely approximate thickness of the excised skin. Insertion depths were evaluated using optical coherence tomography (OCT) using either a force applied by a Texture Analyser or by a group of human volunteers. The obtained insertion depths were, in general, slightly lower, especially for higher forces, for PF than for skin. However, this difference was not a large, being less than the 10% of the needle length. Therefore, all these data indicate that this model membrane could be a good alternative to biological tissue for MN insertion studies. As an alternative method to OCT, light microscopy was used to evaluate the insertion depths of MN in the model membrane. This provided a rapid, simple method to compare different MN formulations. The use of Parafilm M®, in conjunction with a standardised force/time profile applied by a Texture Analyser, could provide the basis for a rapid MN quality control test suitable for in-process use. It could also be used as a comparative test of insertion efficiency between candidate MN formulations.
The Sierra Nevada of the central Betic Cordillera is a 3000
m-high mountain range surrounded by Neogene–Quaternary sedimentary basins, having been uplifted since Late Miocene times. The southern and ...western mountain fronts of the Sierra Nevada are fault-bounded, while the northern one is an unconformity between the Neogene–Quaternary sediments of the Guadix–Baza basin and the metamorphic rocks of the Nevado–Filabride complex. We have carried out a geomorphic study by examining drainage patterns and characteristics of mountain fronts in order to reveal areal variations and styles of rock uplift. Mountain front sinuosity (
S
mf), area–altitude relations (hypsometric curves), and valley floor entrenchment differ significantly between the northern, western, and southern mountain fronts. The lack of important faults along the northern Sierra Nevada mountain front, together with the elevated topographic position of the Guadix–Baza basin (average altitude is around 1100
m), points to similar uplift of both geomorphic units (sierra and basin) in a single large-scale crustal block. The asymmetry factors show systematic asymmetries at both sides of the Lanjarón River, probably due to the presence of an active NNE–SSW oriented antiform in the western Sierra Nevada. Finally, river profiles indicate maximal river entrenchment in the western part of the Sierra Nevada, probably related to the uplift of the footwall of the Padul–Nigüelas fault-system. Therefore, our geomorphic analysis suggests that the western part of the Sierra Nevada is tectonically active by means of a combination of normal faults along the mountain front and NNE–SSW oriented active folds, which, in turn, likely have a gravitational origin related to the exhumation of the footwall of the normal fault-system.
OBJECTIVES
To investigate the implications of obtaining one or more low scores on a battery of cognitive tests on diagnosing mild cognitive impairment (MCI).
DESIGN
Observational longitudinal study.
...SETTING
Alzheimer's Disease Neuroimaging Initiative.
PARTICIPANTS
Normal controls (NC, n = 280) and participants with MCI (n = 415) according to Petersen criteria were reclassified using the Jak/Bondi criteria and number of impaired tests (NIT) criteria.
MEASUREMENTS
Diagnostic statistics and hazard ratios of progression to Alzheimer's disease (AD) were compared according to diagnostic criteria.
RESULTS
The NIT criteria were a better predictor of progression to AD than the Petersen or Jak/Bondi criteria, with optimal sensitivity, specificity, and positive and negative predictive value.
CONCLUSION
Considering normal variability in cognitive test performance when diagnosing MCI may help identify individuals at greatest risk of progression to AD with greater certainty.
A microwave (MW)‐assisted crosslinking process to prepare hydrogel‐forming microneedle (MN) arrays was evaluated. Conventionally, such MN arrays are prepared using processes that includes a thermal ...crosslinking step. Polymeric MN arrays were prepared using poly(methyl vinyl ether‐alt‐maleic acid) crosslinked by reaction with poly(ethylene glycol) over 24 h at 80 °C. Polymeric MN arrays were prepared to compare conventional process with the novel MW‐assisted crosslinking method. Infrared spectroscopy was used to evaluate the crosslinking degree, evaluating the area of the carbonyl peaks (2000–1500 cm−1). It was shown that, by using the MW‐assisted process, MN with a similar crosslinking degree to those prepared conventionally can be obtained in only 45 min. The effects of the crosslinking process on the properties of these materials were also evaluated. For this purpose swelling kinetics, mechanical characterisation, and insertion studies were performed. The results suggest that MN arrays prepared using the MW assisted process had equivalent properties to those prepared conventionally but can be produced 30 times faster. Finally, an in vitro caffeine permeation across excised porcine skin was performed using conventional and MW‐prepared MN arrays. The release profiles obtained can be considered equivalent, delivering in both cases 3000–3500 μg of caffeine after 24 h.
This study shows the advantages of a microwave assisted crosslinking process for the preparation of hydrogel‐forming microneedle (MN) arrays. The arrays prepared using the microwave assisted process have equivalent properties to those prepared conventionally but can be produced 30 times faster. Thus, the use of microwave radiation significantly reduces the time required for MN preparation and, in addition, microwave thermal processes are cheaper and quicker than conventional (oven) heating. Therefore, the findings in this paper are of interest for MN crosslinking applications, leading to shorter, cheaper, and greener manufacturing processes.
We describe, for the first time the use of hydrogel-forming microneedle (MN) arrays for minimally-invasive extraction and quantification of drug substances and glucose from skin in vitro and in vivo. ...MN prepared from aqueous blends of hydrolysed poly(methyl-vinylether-co-maleic anhydride) (11.1% w/w) and poly(ethyleneglycol) 10,000 daltons (5.6% w/w) and crosslinked by esterification swelled upon skin insertion by uptake of fluid. Post-removal, theophylline and caffeine were extracted from MN and determined using HPLC, with glucose quantified using a proprietary kit. In vitro studies using excised neonatal porcine skin bathed on the underside by physiologically-relevant analyte concentrations showed rapid (5 min) analyte uptake. For example, mean concentrations of 0.16 μg/mL and 0.85 μg/mL, respectively, were detected for the lowest (5 μg/mL) and highest (35 μg/mL) Franz cell concentrations of theophylline after 5 min insertion. A mean concentration of 0.10 μg/mL was obtained by extraction of MN inserted for 5 min into skin bathed with 5 μg/mL caffeine, while the mean concentration obtained by extraction of MN inserted into skin bathed with 15 μg/mL caffeine was 0.33 μg/mL. The mean detected glucose concentration after 5 min insertion into skin bathed with 4 mmol/L was 19.46 nmol/L. The highest theophylline concentration detected following extraction from a hydrogel-forming MN inserted for 1 h into the skin of a rat dosed orally with 10 mg/kg was of 0.363 μg/mL, whilst a maximum concentration of 0.063 μg/mL was detected following extraction from a MN inserted for 1 h into the skin of a rat dosed with 5 mg/kg theophylline. In human volunteers, the highest mean concentration of caffeine detected using MN was 91.31 μg/mL over the period from 1 to 2 h post-consumption of 100 mg Proplus® tablets. The highest mean blood glucose level was 7.89 nmol/L detected 1 h following ingestion of 75 g of glucose, while the highest mean glucose concentration extracted from MN was 4.29 nmol/L, detected after 3 hours skin insertion in human volunteers. Whilst not directly correlated, concentrations extracted from MN were clearly indicative of trends in blood in both rats and human volunteers. This work strongly illustrates the potential of hydrogel-forming MN in minimally-invasive patient monitoring and diagnosis. Further studies are now ongoing to reduce clinical insertion times and develop mathematical algorithms enabling determination of blood levels directly from MN measurements.
The placenta is the chief regulator of nutrient supply to the growing embryo during gestation. As such, adequate placental function is instrumental for developmental progression throughout ...intrauterine development. One of the most common complications during pregnancy is insufficient growth of the fetus, a problem termed intrauterine growth restriction (IUGR) that is most frequently rooted in a malfunctional placenta. Together with conventional gene targeting approaches, recent advances in screening mouse mutants for placental defects, combined with the ability to rapidly induce mutations
and
by CRISPR-Cas9 technology, has provided new insights into the contribution of the genome to normal placental development. Most importantly, these data have demonstrated that far more genes are required for normal placentation than previously appreciated. Here, we provide a summary of common types of placental defects in established mouse mutants, which will help us gain a better understanding of the genes impacting on human placentation. Based on a recent mouse mutant screen, we then provide examples on how these data can be mined to identify novel molecular hubs that may be critical for placental development. Given the close association between placental defects and abnormal cardiovascular and brain development, these functional nodes may also shed light onto the etiology of birth defects that co-occur with placental malformations. Taken together, recent insights into the regulation of mouse placental development have opened up new avenues for research that will promote the study of human pregnancy conditions, notably those based on defects in placentation that underlie the most common pregnancy pathologies such as IUGR and pre-eclampsia.
Intersectionality theory combined with an analysis of individual heterogeneity and discriminatory accuracy (AIHDA) can facilitate our understanding of health disparities. This enables the application ...of proportionate universalism for resource allocation in public health. Analyzing self-rated health (SRH) in Sweden, we show how an intersectional perspective allows for a detailed mapping of health inequalities while avoiding simplification and stigmatization based on indiscriminate interpretations of differences between group averages.
We analyzed participants (n=133,244) in 14 consecutive National Public Health Surveys conducted in Sweden in 2004-2016 and 2018. Applying AIHDA, we investigated the risk of bad SRH across 12 intersectional strata defined by gender, income and migration status, adjusted by age and survey year. We calculated odds ratios (with 95% confidence intervals) to evaluate between-strata differences, using native-born men with high income as the comparison reference. We calculated the area under the receiver operating characteristic curve (AU-ROC) to evaluate the discriminatory accuracy of the intersectional strata for identifying individuals according to their SRH status.
The analysis of intersectional strata showed clear average differences in the risk of bad SRH. For instance, the risk was seven times higher for immigrated women with low income (OR 7.00 95% CI 6.14-7.97) than for native men with high income. However, the discriminatory accuracy of the intersectional strata was small (AU-ROC=0.67).
The intersectional AIHDA approach provides more precise information on the existence (or the absence) of health inequalities, and can guide public health interventions according to the principle of proportionate universalism. The low discriminatory accuracy of the intersectional strata found in this study warrants universal interventions rather than interventions exclusively focused on strata with a higher average risk of bad SRH.
•Linearly constrained programs.•Mixed-integer linearly constrained programs.•Linearly constrained semi-infinite programs.•Convexly constrained programs (under affine perturbations).•Conic linearly ...constrained programs.
The radius of robust feasibility provides a numerical value for the largest possible uncertainty set that guarantees feasibility of a robust counterpart of a mathematical program with uncertain constraints. The objective of this review of the state-of-the-art in this field is to present this useful tool of robust optimization to its potential users and to avoid undesirable overlapping of research works on the topic as those we have recently detected. In this paper we overview the existing literature on the radius of robust feasibility in continuous and mixed-integer linearly constrained programs, linearly constrained semi-infinite programs, convexly constrained programs, and conic linearly constrained programs. We also analyze the connection between the radius of robust feasibility and the distance to ill-posedness for different types of uncertain mathematical programs.
Plants develop responses to abiotic stresses, like Fe deficiency. Similarly, plants also develop responses to cope with biotic stresses provoked by biological agents, like pathogens and insects. Some ...of these responses are limited to the infested damaged organ, but other responses systemically spread far from the infested organ and affect the whole plant. These latter responses include the Systemic Acquired Resistance (SAR) and the Induced Systemic Resistance (ISR). SAR is induced by pathogens and insects while ISR is mediated by beneficial microbes living in the rhizosphere, like bacteria and fungi. These root-associated mutualistic microbes, besides impacting on plant nutrition and growth, can further boost plant defenses, rendering the entire plant more resistant to pathogens and pests. In the last years, it has been found that ISR-eliciting microbes can induce both physiological and morphological responses to Fe deficiency in dicot plants. These results suggest that the regulation of both ISR and Fe deficiency responses overlap, at least partially. Indeed, several hormones and signaling molecules, like ethylene (ET), auxin, and nitric oxide (NO), and the transcription factor MYB72, emerged as key regulators of both processes. This convergence between ISR and Fe deficiency responses opens the way to the use of ISR-eliciting microbes as Fe biofertilizers as well as biopesticides. This review summarizes the progress in the understanding of the molecular overlap in the regulation of ISR and Fe deficiency responses in dicot plants. Root-associated mutualistic microbes, rhizobacteria and rhizofungi species, known for their ability to induce morphological and/or physiological responses to Fe deficiency in dicot plant species are also reviewed herein.
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