Impact of COVID-19 on the Utilization of Maternal and Child Health Services at a Regional Referral Hospital in Kenya.

Background and Objective: Pandemics, like COVID-19, disrupt healthcare, potentially reversing progress in various disease areas. The impact on maternal and child health (MCH) services in Kenya during the pandemic is yet to be determined. Recognizing this impact is crucial for formulating policies and programs that minimize disruptions in reproductive health services during future health crises. The purpose of this study was to determine the effect of COVID-19 on the uptake of MCH services at Thika Level V Hospital, a regional referral hospital in Kenya. Methods: In this cross-sectional mixed methods study, we reviewed antenatal clinic (ANC), MCH, and family planning (FP) registers for data on the uptake of the various services during the COVID-19 pandemic (July to October 2020) compared to a year before the COVID-19 pandemic (July to October 2019). MCH clients (N = 60) and healthcare workers (N = 19) were interviewed about the impact of the pandemic on MCH services at the hospital. Differences in clinic attendance before and during the pandemic were compared using the student t-test. Thematic analysis was conducted on the interview responses. Results: The number of MCH/FP clients dropped from 12,915 pre-pandemic to 7,429 during the pandemic. Significant differences were noted in ANC revisits (p = 0.026) and those completing the World Health Organization recommended minimum of four ANC visits (p<0.001) during the COVID-19 pandemic. The number of revisits at the child welfare clinic was also significantly lower (p = 0.004) during the COVID-19 lockdown period. MCH clients stated that the decline in the uptake of MCH services was attributable to the fear of contracting disease, financial difficulties, and strain on the healthcare workforce. Conclusion and Global Health Implications: This study found a decline in access to MCH/FP services during the COVID-19 crisis with the potential to reverse gains made in securing the safety of the pregnant mother and unborn baby.

Magnetic resonance imaging based finite element modelling of the proximal femur: a short-term in vivo precision study.

Proximal femoral fractures are a serious life-threatening injury with high morbidity and mortality. Magnetic resonance (MR) imaging has potential to non-invasively assess proximal femoral bone strength in vivo through usage of finite element (FE) modelling (a technique referred to as MR-FE). To precisely assess bone strength, knowledge of measurement error associated with different MR-FE outcomes is needed. The objective of this study was to characterize the short-term in vivo precision errors of MR-FE outcomes (e.g., stress, strain, failure loads) of the proximal femur for fall and stance loading configurations using 13 participants (5 males and 8 females; median age: 27 years, range: 21-68), each scanned 3 times. MR-FE models were generated, and mean von Mises stress and strain as well as principal stress and strain were calculated for 3 regions of interest. Similarly, we calculated the failure loads to cause 5% of contiguous elements to fail according to the von Mises yield, Brittle Coulomb-Mohr, normal principal, and Hoffman stress and strain criteria. Precision (root-mean squared coefficient of variation) of the MR-FE outcomes ranged from 3.3% to 11.8% for stress and strain-based mechanical outcomes, and 5.8% to 9.0% for failure loads. These results provide evidence that MR-FE outcomes are a promising non-invasive technique for monitoring femoral strength in vivo.

Long-term monitoring of the fish community in the Minho Estuary (NW Iberian Peninsula).

Background: The paper presents an extensive fish sampling dataset spanning a long-term period from 2010 to 2019. The data were collected in Lenta Marina, an upstream area in the Minho Estuary of the NW Iberian Peninsula, which belongs to a LTSER (Long-Term Socio-Ecological Research) platform. To capture fish, fyke nets were utilised as the sampling method and deployed at Lenta Marina. This dataset offers valuable insights into the abundance of each collected taxa recorded over time. New information: The dataset reports a comprehensive compilation of data on the abundance of fish species observed in the area during the sampling period (includes zeroes when a given taxonomic entity was absent in a given sampling event). It provides a detailed record of the abundances of the fish community through time in a frequent sampling regime (on average, sampling was done every 6 days). The dataset shows that the amount of fish from invasive taxa exceeds the count of fish from native taxa in the Minho Estuary.

Cholinergic Activation of Corticofugal Circuits in the Adult Mouse Prefrontal Cortex.

Acetylcholine (ACh) promotes neocortical output to the thalamus and brainstem by preferentially enhancing the postsynaptic excitability of layer 5 pyramidal tract (PT) neurons relative to neighboring intratelencephalic (IT) neurons. Less is known about how ACh regulates the excitatory synaptic drive of IT and PT neurons. To address this question, spontaneous excitatory postsynaptic potentials (sEPSPs) were recorded in dual recordings of IT and PT neurons in slices of prelimbic cortex from adult female and male mice. ACh (20 µM) enhanced sEPSP amplitudes, frequencies, rise-times, and half-widths preferentially in PT neurons. These effects were blocked by the muscarinic receptor antagonist atropine (1 µM). When challenged with pirenzepine (1 µM), an antagonist selective for M1-type muscarinic receptors, ACh instead reduced sEPSP frequencies, suggesting that ACh may generally suppress synaptic transmission in the cortex via non-M1 receptors. Cholinergic enhancement of sEPSPs in PT neurons was not sensitive to antagonism of GABA receptors with gabazine (10 µM) and CGP52432 (2.5 µM) but was blocked by tetrodotoxin (1 µM), suggesting that ACh enhances action-potential-dependent excitatory synaptic transmission in PT neurons. ACh also preferentially promoted the occurrence of synchronous sEPSPs in dual recordings of PT neurons relative to IT-PT and IT-IT parings. Finally, selective chemogenetic silencing of hM4Di-expressing PT, but not commissural IT, neurons blocked cholinergic enhancement of sEPSP amplitudes and frequencies in PT neurons. These data suggest that, in addition to selectively enhancing the postsynaptic excitability of PT neurons, M1 receptor activation promotes corticofugal output by amplifying recurrent excitation within networks of PT neurons.

Food texture and vitamin D influence mouse mandible form and molar roots.

Industrialization influenced several facets of lifestyle, including softer nutrient-poor diets that contributed to vitamin D deficiency in post-industrzialized populations, with concomitantly increased dental problems. Here we simulated a post-industrialized diet in a mouse model to test the effects of diet texture and vitamin D level on mandible and third molar (M3) forms. Mice were raised on a soft diet with vitamin D (VitD) or without it (NoD), or on a hard diet with vitamin D. We hypothesized that a VitD/hard diet is optimal for normal mandible and tooth root form, as well as for timely M3 initiation. Subsets of adult NoD/soft and VitD/soft groups were bred to produce embryos that were micro-computed tomography (µCT) scanned to stage M3 development. M3 stage did not differ between embryos from mothers fed VitD and NoD diets, indicating that vitamin D does not affect timing of M3 onset. Sacrificed adult mice were µCT-scanned, their mandibles 3D-landmarked and M3 roots were measured. Principal component (PC) analysis described the largest proportion of mandible shape variance (PC1, 30.1%) related to diet texture, and nominal shape variance (PC2, 13.8%) related to vitamin D. Mice fed a soft diet had shorter, relatively narrower, and somewhat differently shaped mandibles that recapitulated findings in human populations. ANOVA and other multivariate tests found significantly wider M3 roots and larger root canals in mice fed a soft diet, with vitamin D having little effect. Altogether our experiments using a mouse model contribute new insights about how a post-industrial diet may influence human craniodental variation.

Cholinergic activation of corticofugal circuits in the adult mouse prefrontal cortex.

In layer 5 of the neocortex, ACh promotes cortical output to the thalamus and brainstem by preferentially enhancing the postsynaptic excitability of pyramidal tract (PT) neurons relative to neighboring intratelencephalic (IT) neurons. Less is known about how ACh regulates the excitatory synaptic drive of IT and PT neurons. To address this question, spontaneous excitatory postsynaptic potentials (sEPSPs) were recorded in pairs of IT and PT neurons in slices of prelimbic cortex from adult female and male mice. ACh (20 µM) enhanced sEPSP amplitudes, frequencies, rise-times, and half-widths preferentially in PT neurons. These effects were blocked by the muscarinic acetylcholine receptor antagonist atropine (1 µM). When challenged with pirenzepine (1 µM), an antagonist selective for M1-type muscarinic receptors, ACh instead reduced sEPSP frequencies. The cholinergic increase in sEPSP amplitudes and frequencies in PT neurons was not sensitive to blockade of GABAergic receptors with gabazine (10 µM) and CGP52432 (2.5 µM), but was blocked by tetrodotoxin (1 µM), suggesting that ACh enhances action-potential-dependent excitatory synaptic transmission in PT neurons. ACh also preferentially promoted the occurrence of synchronous sEPSPs in pairs of PT neurons relative to IT-PT and IT-IT pairs. Finally, selective chemogenetic silencing of hM4Di-expressing PT, but not IT, neurons with clozapine-N-oxide (5 µM) blocked cholinergic enhancement of sEPSP amplitudes and frequencies in PT neurons. These data suggest that, in addition to enhancing the postsynaptic excitability of PT neurons, M1 receptor activation promotes corticofugal output by preferentially amplifying recurrent excitation within networks of PT neurons.

Diverse environmental cues drive the size of reproductive aggregation in a rheophilic fish.

BACKGROUND: Animal migrations are periodic and relatively predictable events, and their precise timing is essential to the reproductive success. Despite large scientific effort in monitoring animal reproductive phenology, identification of complex environmental cues that determine the timing of reproductive migrations and temporal changes in the size of reproductive aggregations in relation to environmental variables is relatively rare in the current scientific literature. METHODS: We tagged and tracked 1702 individuals of asp (Leuciscus aspius), a large minnow species, and monitored with a resolution of one hour the size of their reproductive aggregations (counts of sexes present at the breeding grounds standardized by the sum of individuals in the season) over seven breeding seasons using passive integrated transponder tag systems. We examined the size of reproductive aggregations in relation to environmental cues of day number within a reproductive season (intra-year seasonality), water temperature, discharge, hour in a day (intra-day pattern), temperature difference between water and air, precipitation, atmospheric pressure, wind speed and lunar phase. A generalized additive model integrating evidence from seven breeding seasons and providing typical dynamics of reproductive aggregations was constructed. RESULTS: We demonstrated that all environmental cues considered contributed to the changes in the size of reproductive aggregations during breeding season, and that some effects varied during breeding season. Our model explained approximately 50% of the variability in the data and the effects were sex-dependent (models of the same structure were fitted to each sex separately, so that we effectively stratified on sex). The size of reproductive aggregations increased unimodally in response to day in season, correlated positively with water temperature and wind speed, was highest before and after the full moon, and highest at night (interacting with day in a season). Males responded negatively and females positively to increase in atmospheric pressure. CONCLUSION: The data demonstrate complex utilization of available environmental cues to time reproductive aggregations in freshwater fish and their interactions during the reproductive season. The study highlights the need to acquire diverse data sets consisting of many environmental cues to achieve high accuracy of interpretation of reproductive timing.

Desiccant Dusts, With and Without Bioactive Botanicals, Lethal to Rhipicephalus (Boophilus) microplus Canestrini (Ixodida: Ixodidae) in the Laboratory and on Cattle.

The exotic southern cattle fever tick, Rhipicephalus (Boophilus) microplus (Canestrini) (Ixodida: Ixodidae), since its eradication from the United States in 1943, made a strong incursion into Texas, beginning 2016. The pest is arguably the most economically detrimental ectoparasite of cattle, Bos taurus L., worldwide. Current R. (B.) microplus control mostly relies on conventional synthetic acaricides to which the ixodid has been developing resistance. Our study demonstrates that commercially available desiccant dust products, with and without bioactive botanical additives, are strongly lethal, when applied dry, against larval R. (B.) microplus in the laboratory, and after being released on dust-treated cattle. Deadzone (renamed Celite 610, a diatomaceous earth product), Drione (silica gel + pyrethrins + piperonyl butoxide synergist), and EcoVia (silica gel + thyme oil), each prophylactically prevented larval R. (B.) microplus from attaching to and feeding on stanchioned calves. Desiccant dust-based products are less likely than conventional synthetic acaricides to decline in terms of efficacy as a result of ixodid resistance, and other desiccant dust advantages, including extended residual, flexibility in terms of application methods, environmental, animal, and human safety, and possible compatibility with organic, or 'green', production systems, are discussed. We anticipate that the desiccant dusts we evaluated, and others not included in this study (e.g., kaolin, perlite, and silica gel) will be effective when used with other control tactics in integrated pest management approaches for controlling R. (B.) microplus (and other ixodid species).

Lethal Effects of Imergard WP, a Perlite-based Dust, on Amblyomma americanum (Ixodida: Ixodidae) Larvae and Nymphs.

As resistance in economically and medically important ixodids (hard ticks, Ixodida: Ixodidae) to conventional synthetic toxin-based acaricides has become increasingly widespread, research efforts to identify alternative control tactics have intensified. Laboratory bioassays on the lone star tick, Amblyomma americanum (L.), as a model for other ixodid species, were conducted to assess the efficiency of Imergard WP perlite-based dust versus CimeXa, a silica gel-based insecticidal product that is highly effective against ixodid larvae and nymphs. Each of the two inert desiccant dusts immobilized A. americanum larvae and nymphs within 4-6 h, and killed 100% of the ixodids by 24 h after contact by brief immersion in dry dusts, and after they crawled ≈7.3 cm across a filter paper disc treated with the dusts. Contact by crawling on a dried aqueous film of the dusts, however, did not immobilize and kill the ixodids by 24 h. Similar to silica gel-based desiccant dust, dry perlite-based Imergard WP dust might prophylactically protect cattle and other animals from medically and agriculturally important ixodid pests. Perlite can potentially be stored indefinitely, it can retain its lethal properties for as long as adequate amounts remain on a substrate, and it might be acceptable for limited application in environmentally sensitive habitats.

Alzheimer's disease medication use and adherence patterns by race and ethnicity.

BACKGROUND: We examined racial and ethnic differences in medication use for a representative US population of patients with Alzheimer's disease and related dementias (ADRD). METHODS: We examined cholinesterase inhibitors and memantine initiation, non-adherence, and discontinuation by race and ethnicity, using data from the 2000-2016 Health and Retirement Study linked with Medicare and Medicaid claims. RESULTS: Among newly diagnosed ADRD patients (n = 1299), 26% filled an ADRD prescription ≤90 days and 36% ≤365 days after diagnosis. Among individuals initiating ADRD-targeted treatment (n = 1343), 44% were non-adherent and 24% discontinued the medication during the year after treatment initiation. Non-Hispanic Blacks were more likely than Whites to not adhere to ADRD medication therapy (odds ratio: 1.50 [95% confidence interval: 1.07-2.09]). DISCUSSION: Initiation of ADRD-targeted medications did not vary by ethnoracial group, but non-Hispanic Blacks had lower adherence than Whites. ADRD medication non-adherence and discontinuation were substantial and may relate to cost and access to care. HIGHLIGHTS: Initiation of anti-dementia medications among newly diagnosed Alzheimer's disease and related dementias (ADRD) patients was low in all ethnoracial groups. ADRD medication non-adherence and discontinuation were substantial and may relate to cost and access to care. Compared to Whites, Blacks and Hispanics had lower use, poorer treatment adherence, and more frequent discontinuation of ADRD medication, but when controlling for disease severity and socioeconomic factors, racial disparities diminish. Our findings demonstrate the importance of adjusting for socioeconomic characteristics and disease severity when studying medication use and adherence in ADRD patients.

Low-Value Prostate-Specific Antigen Test for Prostate Cancer Screening and Subsequent Health Care Utilization and Spending.

Importance: Delivering low-value care can lead to unnecessary follow-up services and associated costs, and such care cascades have not been well examined in common clinical scenarios. Objective: To evaluate the utilization and costs of care cascades of prostate-specific antigen (PSA) tests for prostate cancer screening, as the routine use of which among asymptomatic men aged 70 years and older is discouraged by multiple guidelines. Design, Setting, and Participants: This cross-sectional study included men aged 70 years and older without preexisting prostate conditions enrolled in a Medicare Advantage plan during January 2016 to December 2018 with at least 1 outpatient visit. Medical billing claims data from the deidentified OptumLabs Data Warehouse were used. Data analysis was conducted from September 2020 to August 2021. Exposures: At least 1 claim for low-value PSA tests for prostate cancer screening during the observation period. Main Outcomes and Measures: Utilization of and spending on low-value PSA cancer screening and associated care cascades and the difference in overall health care utilization and spending among individuals receiving low-value PSA cancer screening vs those who did not, adjusting for observed characteristics using inverse probability of treatment weighting. Results: Of 995 442 men (mean [SD] age, 78.0 [5.6] years) aged 70 years or older in a Medicare Advantage plan included in this study, 384 058 (38.6%) received a low-value PSA cancer screening. Utilization increased for each subsequent cohort from 2016 to 2018 (49 802 of 168 951 [29.4%] to 134 404 of 349 228 [38.5%] to 199 852 of 477 203 [41.9%]). Among those receiving initial low-value PSA cancer screening, 241 188 of 384 058 (62.8%) received at least 1 follow-up service. Repeated PSA testing was the most common, and 27 268 (7.1%) incurred high-cost follow-up services, such as imaging, radiation therapy, and prostatectomy. Utilization and spending associated with care cascades also increased from 2016 to 2018. For every $1 spent on a low-value PSA cancer screening, an additional $6 was spent on care cascades. Despite avoidable care cascades, individuals who received low-value PSA cancer screening were not associated with increased overall health care utilization and spending during the 1-year follow-up period compared with an unscreened population. Conclusions and Relevance: In this cross-sectional study, low-value PSA tests for prostate cancer screening remained prevalent among Medicare Advantage plan enrollees and were associated with unnecessary expenditures due to avoidable care cascades. Innovative efforts from clinicians and policy makers, such as payment reforms, to reduce initial low-value care and avoidable care cascades are warranted to decrease harm, enhance equity, and improve health care efficiency.

Different hosts in different lakes: prevalence and population genetic structure of plerocercoids of Ligula intestinalis (Cestoda) in Czech water bodies.

Ligula intestinalis (Linnaeus, 1758) is a tapeworm parasite with a worldwide distribution that uses a wide variety of fish species as its second intermediate host. In the present study, we investigated the prevalence and population genetic structure of plerocercoids of L. intestinalis in five common cyprinoid species, roach Rutilus rutilus (Linnaeus), freshwater bream Abramis brama (Linnaeus), white bream Blicca bjoerkna (Linnaeus), bleak Alburnus alburnus (Linnaeus), and rudd Scardinius erythrophthalmus (Linnaeus), collected in six water bodies of the Czech Republic (Milada, Most, Medard, Jordán, Rímov and Lipno). Of the six study sites, the highest frequency of parasitism was recorded in Lake Medard (15%). The overall prevalence rate among the species was as follows: roach > rudd ≥ freshwater bream > bleak > white bream. Two mitochondrial genes (cytb and COI) were used to compare the population genetic structure of parasite populations using selected samples from the five fish species. The results of the phylogenetic analysis indicated that all populations of L. intestinalis were placed in Clade A, previously identified as the most common in Europe. At a finer scale, haplotype network and PCoA analyses indicated the possible emergence of host specificity of several mtDNA haplotypes to the freshwater bream. Moreover, pairwise Fixation indices (FST) revealed a significant genetic structure between the parasite population in freshwater bream and other host species. Parasite populations in roach not only showed the highest rate of prevalence but also depicted a maximum number of shared haplotypes with populations from bleak and rudd. Our results suggest that recent ecological differentiation might have influenced tapeworm populations at a fine evolutionary scale. Thus, the differences in prevalence between fish host species in different lakes might be influenced not only by the parasite's ecology, but also by its genetic diversity.

Body condition and energy content of the shore crab Carcinus maenas L. in a temperate coastal system: the cost of barnacle epibiosis.

The impact of barnacle epibionts on the condition of the shore crab Carcinus maenas was studied for the western Wadden Sea population. Approximately 39% of the crabs were fouled with the barnacle Balanus crenatus. Although the morphological Fulton's K condition decreased by 5.8% in fouled crabs, Linear Mixed-Effects Models (LMM) showed that only the energetic condition of the crabs was significantly affected by fouling. The energy density of fouled crabs was consistently poorer (4.1% in AFDW; 8.7% in dry weight) than that of non-fouled crabs, especially in females and green forms in dry weight (12.8% and 11.4% reduction, respectively). Cumulative infection with Sacculina carcini, detected in 4.5% of the fouled crabs, additionally reduced by 14.3% the energy density in dry weight and almost to half of the total energy of the fouled crabs. Impacts of energy density reduction on crabs' growth and reproduction are discussed.

State-Level Variation In Low-Value Care For Commercially Insured And Medicare Advantage Populations.

Low-value care is a major source of health care inefficiency in the US. Our analysis of 2009-19 administrative claims data from OptumLabs Data Warehouse found that low-value care and associated spending remain prevalent among commercially insured and Medicare Advantage enrollees. The aggregated prevalence of twenty-three low-value services was 1,920 per 100,000 eligible enrollees, which amounted to $3.7 billion in wasteful expenditures during the study period. State-level variation in spending was greater than variation in utilization, and much of the variation in spending was driven by differences in average procedure prices. If the average price for twenty-three low-value services among the top ten states in spending were set to the national average, their spending would decrease by 19.8 percent (from $735,000 to $590,000 per 100,000 eligible enrollees). State-level actions to improve the routine measurement and reporting of low-value care could identify sources of variation and help design state-specific policies that lead to better patient-centered outcomes, enhanced equity, and more efficient spending.

Boom and bust: Simulating the effects of climate change on the population dynamics of a global invader near the edge of its native range.

Despite the increasing awareness of climate change, few studies have used the Intergovernmental Panel on Climate Change (IPCC) scenarios to simulate the effects of climate change on estuarine populations of crustaceans. The objective of this study was to investigate the effects of temperature and salinity fluctuations on the population dynamics of the shore crab Carcinus maenas at the southern edge of its native range. To this end, a population dynamics model was developed based on experimental and literature data on the biology, ecology and physiology of the species. Results showed that the shore crab will be more affected by changes in temperature than in salinity. The parameter sensitivity analysis revealed that the larval phase of the species is the most sensitive stage of the shore crab life cycle. Three IPCC scenarios (SSP1-2.6, SSP2-4.5, and SSP3-8.5) were used to simulate the effects of temperature increase on the population of C. maenas in the near- (2040), mid- (2060), and long-term (2100). Two scenarios of drought conditions accompanied by the estimated salinity change were also simulated (10 % and 40 % drought). Results suggested that slight increases in temperature (up to 2 °C) lead to a strong increase on the density of C. maenas in the mid-term, while further temperature increases lead to a decline or local extinction of the shore crab population at the southern edge of its distribution range. Results indicated that a salinity increase in the estuary had a negative effect on the shore crab population. Given the importance of the species to temperate coastal ecosystems, both population increase and local extinction are likely to have significant impacts on estuarine communities and food webs, with unknown ecological and socioeconomic consequences.

Sacculina carcini impact on energy content of the shore crab Carcinus maenas L.

The impact of Sacculina carcini infection on the nutritional status of the shore crab Carcinus maenas was investigated in the western Dutch Wadden Sea for a period of 20 months. About 3.3% of the population was sacculinized, i.e. externally infected with S. carcini and only 0.7% presented scars of previous infection. The results of mixed linear models showed that sacculinized and non-sacculinized crabs had similar morphometric condition, while the energy density of parasitized crabs (externa excluded) was significantly reduced by about 4.3% overall, and by up to 5.8% in crabs under 40 mm carapace width. However, when Sacculina externa was included in the energy determinations, the difference in energy density decreased to 1.2%, while total energy content of the pair infected crab-parasite including externa was 30.8% higher than non-sacculinized crabs of similar size. The total energy content of ovigerous females (eggs included) was even higher, near doubling the energy of similar-sized crabs. The same way, total energy content of Sacculina externa was about 4 times lower than total energy of egg mass. The results suggest that the rhizocephalan parasite is efficient in consuming the energy that the host may allocate for growth and maintenance, but require future studies to disentangle the impact of the degree of internal infection and the implications for the dynamics of the population.

Cost-effectiveness of DPYD Genotyping Prior to Fluoropyrimidine-based Adjuvant Chemotherapy for Colon Cancer.

BACKGROUND: Adjuvant fluoropyrimidine-based chemotherapy substantially reduces recurrence and mortality after resection of stage 3 colon cancer. While standard doses of 5-fluorouracil and capecitabine are safe for most patients, the risk of severe toxicity is increased for the approximately 6% of patients with dihydropyimidine dehydrogenase (DPD) deficiency caused by pathogenic DPYD gene variants. Pre-treatment screening for pathogenic DPYD gene variants reduces severe toxicity but has not been widely adopted in the United States. METHODS: We conducted a cost-effectiveness analysis of DPYD genotyping prior to fluoropyrimidine-based adjuvant chemotherapy for stage 3 colon cancer, covering the c.1129-5923C>G (HapB3), c.1679T>G (*13), c.1905+1G>A (*2A), and c.2846A>T gene variants. We used a Markov model with a 5-year horizon, taking a United States healthcare perspective. Simulated patients with pathogenic DPYD gene variants received reduced-dose fluoropyrimidine chemotherapy. The primary outcome was the incremental cost-effectiveness ratio (ICER) for DPYD genotyping. RESULTS: Compared with no screening for DPD deficiency, DPYD genotyping increased per-patient costs by $78 and improved survival by 0.0038 quality-adjusted life years (QALYs), leading to an ICER of $20,506/QALY. In 1-way sensitivity analyses, The ICER exceeded $50,000 per QALY when the cost of the DPYD genotyping assay was greater than $286. In probabilistic sensitivity analysis using a willingness-to-pay threshold of $50,000/QALY DPYD genotyping was preferred to no screening in 96.2% of iterations. CONCLUSION: Among patients receiving adjuvant chemotherapy for stage 3 colon cancer, screening for DPD deficiency with DPYD genotyping is a cost-effective strategy for preventing infrequent but severe and sometimes fatal toxicities of fluoropyrimidine chemotherapy.

Performance of a Multianalyte 'Rule-Out' Assay in Pregnant Individuals With Suspected Preeclampsia.

BACKGROUND: The ability to diagnose preeclampsia clinically is suboptimal. Our objective was to validate a novel multianalyte assay and characterize its performance, when intended for use as an aid to rule-out preeclampsia. METHODS: Prospective, multicenter cohort study of pregnant individuals presenting between 280/7 and 366/7 weeks' with preeclampsia-associated signs and symptoms. Individuals not diagnosed with preeclampsia after baseline evaluation were enrolled in the study cohort, with those who later developed preeclampsia, classified as cases and compared with a negative control group who did not develop preeclampsia. Individuals with assay values at time of enrollment ≥0.0325, determined using a previously developed algorithm, considered at risk. The primary analysis was the time to develop preeclampsia assessed using a multivariate Cox regression model. RESULTS: One thousand thirty-six pregnant individuals were enrolled in the study cohort with an incidence of preeclampsia of 30.3% (27.6%-33.2%). The time to develop preeclampsia was shorter for those with an at-risk compared with negative assay result (log-rank P<0.0001; adjusted hazard ratio of 4.81 [3.69-6.27, P<0.0001]). The performance metrics for the assay to rule-out preeclampsia within 7 days of enrollment showed a sensitivity 76.4% (67.5%-83.5%), negative predictive value 95.0% (92.8%-96.6%), and negative likelihood ratio 0.46 (0.32-0.65). Assay performance improved if delivery occurred <37 weeks and for individuals enrolled between 28 and 35 weeks. CONCLUSIONS: We confirmed that a novel multianalyte assay was associated with the time to develop preeclampsia and has a moderate sensitivity and negative likelihood ratio but high negative predictive value when assessed as an aid to rule out preeclampsia within 7 days of enrollment. REGISTRATION: The study was registered on Clinicaltrials.gov (Identifier NCT02780414).

Postrhinal cortex contributions to the expression of auditory fear conditioning.

The postrhinal cortex (POR), the rodent homologue of the primate parahippocampal cortex (PHC), has been implicated in contextual and spatial processing. For instance, prior studies have demonstrated that permanent lesions of POR impair contextual fear conditioning. In contrast, permanent lesions of POR, specifically prior to training, do not impact auditory fear conditioning. In the current experiments, we examined the role of POR in the expression of auditory fear conditioning by using chemogenetics to silence neural activity in POR at the time of retrieval testing. Considering that extinction is context-dependent, and POR contributes to contextual memory, we hypothesized that POR would be necessary for expression of auditory fear conditioning following extinction. We found that POR inactivation during retrieval impaired freezing to an auditory cue that was tested in the conditioning context (A) after it had been extinguished in a different context (B). However, the involvement of POR was not specific to extinction. POR inactivation also impaired freezing to an auditory fear cue that had not undergone extinction. Thus, while prior studies have identified a role for POR in contextual fear conditioning, the current findings extend the functional role of POR to include the expression of auditory fear conditioning.

Influence of climate change and extreme weather events on an estuarine fish community.

Extreme weather events are becoming more frequent as a result of climate change, and the increasing frequency of these events may lead to significant changes in fish assemblages. In this sense, this work aimed to study the effects of climate change and extreme weather events on fish assemblages in the Rio Minho estuary (Portugal). Between 2010 and 2019, continuous weekly sampling with fyke nets was carried out to assess the dynamics of fish assemblages in the estuary. In addition, temperature and precipitation data were obtained from satellite information to assess the relationship between climatic variables and fish composition, structure, and diversity. Fish populations changed significantly over time, becoming less diverse and largely dominated by a few, mostly invasive species (e.g., carp, goldfish, pumpkinseed, and tench), while the abundance of most native species declined over the years (e.g., panjorca, stickleback, and shad). High temperatures and low precipitation negatively affected native species, while the invasive species benefited from increased temperatures and extreme weather events (droughts and floods).