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Procedure duration is an important predictor of patient outcomes in surgery. However, the relationship between procedure duration and adverse events in congenital cardiac catheterization is largely unexplored.
Methods:
All cases entered into the Congenital Cardiac Catheterization Project on Outcomes from 2014 to 2017 were included. Cases were ordered from shortest to longest case length, minus time spent managing adverse events, for each case type. The outcomes, Level 3bc/4/5 and 4/5 adverse event rates, were calculated for cases above and below the 75th percentile for case length. To identify an independent relationship between case length and outcomes, the case length percentile was added to the CHARM II risk model.
Results:
Among 14,704 catheterizations, longer cases (>75th percentile for case length) had Level 4/5 rates that were 2.2% and 2.7% compared to cases ≤75th percentile with adverse event rates of 0.9% and 1.4% for diagnostic and interventional cases, respectively. Level 3bc/4/5 rates were 5.0% and 8.4% in longer cases compared to 2.4% and 5.4% for diagnostic and interventional cases, respectively. After adding case length to the CHARM II risk model, case length 50th–75th percentile had an odds ratio (OR) of 1.4, 75th–90th percentile an OR of 1.56, and >90th percentile an OR of 2.24 as compared to cases with case length <50th percentile (p ≤ 0.001 for all).
Conclusions:
Longer case lengths are associated with clinically important and life-threatening adverse events in congenital cardiac catheterization, even after accounting for known risk factors. Case length may be an important target for future quality improvement work.
In the winter of 2022–2023, hundreds of the Atlantic puffins (Fratercula arctica) appeared dead in the coast of the Canary Islands, a rare event considering their cold-living habits, normally occupying the North Atlantic Ocean. In this work, investigation about the parasites present in the Atlantic puffins found in the biggest islands of the Archipelago was carried out from a population portion. Necropsies of 39 birds were made and, during the examination of the urinary tracts, helminths were found. Morphoanatomical analysis under microscope allowed to identify them into Renicola genus with high similarity to Renicola sloanei. After that, DNA was extracted and NADH dehydrogenase subunit 1 gene were amplificated by a polymerase chain reaction method followed by sequencing and phylogenetic analysis. The molecular results demonstrated that in fact R. sloanei was the helminth parasite present in the urinary tracts of the Atlantic puffins found in the Canary Islands.
Visceral leishmaniasis (VL) is a tropical disease that can be fatal if acute and untreated. Diagnosis is difficult, the treatment is toxic and prophylactic vaccines do not exist. Leishmania parasites express hundreds of proteins and several of them are relevant for the host's immune system. In this context, in the present study, 10 specific T-cell epitopes from 5 parasite proteins, which were identified by antibodies in VL patients’ sera, were selected and used to construct a gene codifying the new chimeric protein called rCHI. The rCHI vaccine was developed and thoroughly evaluated for its potential effectiveness against Leishmania infantum infection. We used monophosphoryl lipid A (MPLA) and polymeric micelles (Mic) as adjuvant and/or delivery system. The results demonstrated that both rCHI/MPLA and rCHI/Mic significantly stimulate an antileishmanial Th1-type cellular response, with higher production of IFN-γ, TNF-α, IL-12 and nitrite in vaccinated animals, and this response was sustained after challenge. In addition, these mice significantly reduced the parasitism in internal organs and increased the production of IgG2a isotype antibodies. In vivo and in vitro toxicity showed that rCHI is safe for the mammalians, and the recombinant protein also induced in vitro lymphoproliferative response and production of Th1-type cytokines by human cells, which were collected from healthy subjects and treated VL patients. These data suggest rCHI plus MPLA or micelles could be considered as a vaccine candidate against VL.
Rotor-stator flows are known to exhibit instabilities in the form of circular and spiral rolls. While the spirals are known to emanate from a supercritical Hopf bifurcation, the origin of the circular rolls is still unclear. In the present work we suggest a quantitative scenario for the circular rolls as a response of the system to external forcing. We consider two types of axisymmetric forcing: bulk forcing (based on the resolvent analysis) and boundary forcing using direct numerical simulation. Using the singular value decomposition of the resolvent operator the optimal response is shown to take the form of circular rolls. The linear gain curve shows strong amplification at non-zero frequencies following a pseudo-resonance mechanism. The optimal energy gain is found to scale exponentially with the Reynolds number $Re$ (for $Re$ based on the rotation rate and interdisc spacing $H$). The results for both types of forcing are compared with former experimental works and previous numerical studies. Our findings suggest that the circular rolls observed experimentally are the effect of the high forcing gain together with the roll-like form of the leading response of the linearised operator. For high enough Reynolds number it is possible to delineate between linear and nonlinear responses. For sufficiently strong forcing amplitudes, the nonlinear response is consistent with the self-sustained states found recently for the unforced problem. The onset of such non-trivial dynamics is shown to correspond in state space to a deterministic leaky attractor, as in other subcritical wall-bounded shear flows.
The Prof pegmatite is located NW of Revelstoke, British Columbia, Canada on Boulder Mountain. Due to the abundance of petalite, the pegmatite is classified as a petalite subtype Li-Cs-Ta pegmatite or a Group one pegmatite. The Prof pegmatite contains a suite of minerals indicative of a highly evolved pegmatite melt including petalite, elbaite, lepidolite and Nb–Ta oxides. Four textural zones are present: (1) border; (2) intermediate, including (2.1) graphic texture dominant and (2.2) overgrowth dominant, where diverse minerals form rims around one another; (3) central; and (4) quartz. The border zone has a similar mineralogy to the intermediate zone and is interpreted to represent a chilled margin. The intermediate zone has a feldspar, mica, garnet and dravite–schorl dominant composition. The central zone hosts an evolved pegmatite core, which contains the majority of the lithium mineralisation composed of petalite, elbaite and lepidolite. The tourmaline, Nb–Ta oxides and mica within the pegmatite record the geochemical evolution of the melt from more primitive Fe- and Mg-rich minerals to a Li-, Mn- and Nb-rich assemblage indicative of a highly evolved geochemical system. The various pegmatitic textures and extremely fractionated geochemical composition of the pegmatite indicate that the melt was undercooled and crystallised rapidly. Three phases of metasomatism are recognised in the Prof pegmatite: an albitisation event observed cutting primary orthoclase; followed by a transition to a Na–Li–F-rich event mostly containing secondary albite, trilithionite and elbaites; and a sericitisation event.
The Prof pegmatite has a similar mineralogy to known pegmatites at Mount Begbie, 15 km to the south, in particular the notable presence of the rare mineral qitianlingite, petalite, lepidolite and elbaite. Together, these pegmatite bodies form part of an extensive, poorly mapped pegmatite field. Additional work is required to assess the extent and nature of mineralisation within this field.
Efficient evidence generation to assess the clinical and economic impact of medical therapies is critical amid rising healthcare costs and aging populations. However, drug development and clinical trials remain far too expensive and inefficient for all stakeholders. On October 25–26, 2023, the Duke Clinical Research Institute brought together leaders from academia, industry, government agencies, patient advocacy, and nonprofit organizations to explore how different entities and influencers in drug development and healthcare can realign incentive structures to efficiently accelerate evidence generation that addresses the highest public health needs. Prominent themes surfaced, including competing research priorities and incentives, inadequate representation of patient population in clinical trials, opportunities to better leverage existing technology and infrastructure in trial design, and a need for heightened transparency and accountability in research practices. The group determined that together these elements contribute to an inefficient and costly clinical research enterprise, amplifying disparities in population health and sustaining gaps in evidence that impede advancements in equitable healthcare delivery and outcomes. The goal of addressing the identified challenges is to ultimately make clinical trials faster, more inclusive, and more efficient across diverse communities and settings.
Dioctophyme renale, the giant kidney worm, is a nematode related to Trichuris sp and is distributed worldwide. These parasites locate in the kidney of their definitive hosts (mainly belonging to the order Carnivora) and have an indirect life cycle with an annelid as the main intermediate host. Humans are rarely affected, but in those that are, 1 or both kidneys are destroyed. In South America, D. renale is widespread in riparian regions where changing climatic conditions, environmental degradation, and compromised sanitation are increasing the risk of distribution of this parasite, including humans. Here, we provide the descriptions of the genetic diversity of the parasite in the region by analysing 73 adult D. renale samples collected from domestic and wild carnivores. The most common hosts were (Canis lupus familiaris) and maned wolf (Chrysocyon brachyurus Fam. Canidae) among domestic and wild carnivores, respectively. This work shows the descriptions of the genetic diversity of this parasite complementing molecular methods and classical and probabilistic phylogeography. Our results strongly suggest that this parasite has been present on the continent long enough to develop local genetic variants. Also, the phylogenies show transmission between localities and bidirectional transmission between domestic and wild species. We now have new tools to understand the ecological dynamics of this parasite such as molecular markers to study its genetic diversity as well as for identification and reporting in cryptic cases.
Schizotypal personality is a condition suffered by 4% of the population. It is defined by presenting interpersonal, behavioral and perceptual features similar to the clinical features of psychotic disorders, such as schizophrenia, in less intensity and dysfunctionality, but at risk of reaching psychosis.
Objectives
Presentation of a clinical case about a patient with premorbid schizotypal personality traits presenting with an acute psychotic episode.
Methods
Literature review on association between schizotypal personality and psychosis.
Results
A 57-year-old woman with a history of adaptive disorder due to work problems 13 years ago, currently without psychopharmacological treatment, goes to the emergency room brought by the emergency services due to behavioral alteration. She reports that “her husband and son wanted to sexually abuse her”, so she had to run away from home and has been running through the streets of the town without clothes and barefoot.
Her husband relates attitude alterations and extravagant behaviors of years of evolution, such as going on diets of eating only bread for 40 days or talking about exoteric and religious subjects, as believing that the devil got inside her husband through a dental implant. He reports that these behaviors have been accentuated during the last month. She has also created a tarot website, and has even had discussions with several users. She is increasingly suspicious of him, has stopped talking to him and stays in his room all day long, with unmotivated laughter and soliloquies.
It was decided to admit him to Psychiatry and risperidone 4 mg was started. At the beginning, she was suspicious and reticent in the interview. As the days went by, communication improved, she showed a relaxed gesture and distanced herself from the delirious ideation, criticizing the episode.
Conclusions
In recent years, there has been increasing interest in understanding the association between schizotypy and serious mental disorder. Several theories understand schizotypy as a natural continuum of personality that reveals genetic vulnerability and that can lead to psychotic disorder when added to precipitating factors. Other theories define schizotypy as a “latent schizophrenia” where symptoms are contained and expressed in less intensity.
Around 20% evolves to paranoid schizophrenia or other serious mental disorders. It is complex to distinguish between those individuals in whom schizotypy is a prodrome and those in whom it is a stable personality trait. To date, studies applying early psychotherapeutic or pharmacological interventions have had insufficient and contradictory results, and the follow-up and treatment of these individuals could be a stress factor and a stigma. Some studies are looking for reliable markers of evolution to schizophrenia in order to establish adequate protocols for detention, follow-up and treatment.
tardive dysphoria is a relatively new term used to describe the phenomenon of clinical worsening of depression after long-term antidepressant use. Most of the theories proposed to explain this talk about antidepressants tachyphylaxis that implies the loss of efficacy with its prolonged use, or even a pro-depressant effect of antidepressants when used for long periods of time.
Objectives
to explore the concept of tardive dysphoria, potential causes and clinical implications, by making a literature review on the topic. Moreover we pretend to understand the challenges in its diagnosis and treatment.
Methods
bibliographical search in PubMed database, using the key-words “long-term antidepressant”, “tardive dysphoria” and “antidepressant tachyphylaxis”, limited to works published in the last twenty years.
Results
from our search resulted 53 articles, 26 were chosen for further analysis.
Conclusions
the concept of tardive dysphoria is controversial, namely doubt persists if it constitutes a clinical entity by itself caused by long-term antidepressant use or if it simply relates to cases of treatment-resistant depression. We conclude that it is necessary further investigation in this area given the significant implications on clinical practice specifically in the psychopharmacological treatment with antidepressants, which is very common in psychiatric and general practices, with antidepressants being used to treat many mental health conditions.
fibromyalgia is a modern disease, with growing investigation concerning its etiology and treatment. It has become a very prevalent diagnosis and total remission of symptoms is the exception which is dramatic considering the socio-occupational impact of this highly debilitating disease.
Objectives
to review the updates in the pathophysiology and treatment of fibromyalgia, especially when it is refractory to treatment. The authors also intend to better understand where fibromyalgia belongs, is it in psychiatry as a functional disorder or in rheumatology as an auto-immune disease?
Methods
bibliographical search in PubMed database, using the key-words “fibromyalgia” and “psychiatry”, limited to works published in the last 10 years.
Results
from our search resulted 158 articles, from reading of abstracts 30 were chosen for further reading.
Conclusions
concerning the etiology of this disease, on the one hand psychological factors cannot be neglected since there are several studies finding a positive correlation between stressors like history of physical abuse and fibromyalgia in adulthood, on the other hand investigation and meta-analysis have found that the immune-inflammatory response system might be altered with dysregulation of pro and anti-inflammatory cytokines and cell-mediated immunity. Regarding treatment, symptom relief is often unsatisfactory with classical treatment and so adjunct treatment such as electrical neuromodulation and aerobic exercise might, respectively, be effective in reducing pain and depressive symptoms, thereby improving quality of life, and in improving fatigue and in a lesser degree sleep.
Delusional parasitosis, also known as delusional infestation or Ekbom’s syndrome, is a rare psychotic disorder characterized by the false belief that a parasitic skin infestation exists, despite the absence of any medical evidence to support this claim. These patients often see many physicians, so a multidisciplinary approach among clinicians is important. Many patients refuse any treatment due to their firm belief that they suffer from an infestation, not a psychiatric condition, so it is crucial to gain the trust of these patients.
Objectives
The comprehensive review of this clinical case aims to investigate Ekbom syndrome, from a historical, clinical and therapeutic perspective.
Methods
Literature review based on delusional parasitosis.
Results
A 65-year-old woman comes to the psychiatry consultation referred by her primary care physician concerned about being infested by insects that she perceives through scales on her skin for the last three months. She recognizes important impact on her functionality. She is also convinced that her family is being infected too. As psychiatric history she recognizes alcohol abuse in the past (no current consumption) and an episode of persecutory characteristics with a neighbor, more than ten years ago. On psychopathological examination, she shows delusional ideation of parasitosis, with high behavioral repercussions, cenesthetic and cotariform hallucinations, as well as feelings of helplessness and anger. Treatment with Pimozide was started and the patient was referred to dermatology for evaluation, a plan she accepted. Her primary care physician and dermatology specialist were informed about the case and the treatment plan. In the recent reviews, the patient is calmer, however, despite the corroboration of dermatology and in the absence of organic lesions in cranial CT, she is still unsatisfied with the results, remaining firm in her conviction of infestation. It was decided to start treatment with atypical neuroleptics (Aripiprazole), with progressive recovery of her previous functionality.
Conclusions
Despite the increase in the number of studies in recent years, there are still few studies on this type of delirium. The female:male ratio varies in the bibiliography (between 2:1 and 3:1). The onset is usually insidious, generally appearing as a patient who comes to his primary care physician convinced of having parasites in different skin locations. It is usual to observe scratching lesions or even wounds in search of the parasite. In the past, the most used and studied treatment was Pimozide. Currently the treatment of choice is atypical neuroleptics due to their lower side effects. The latest reviews on the prognosis of this disorder show data with percentages of complete recovery between 51% and 70%, and partial responses between 16.5% and 20%. Finally, for a good diagnosis and therapeutic management, it is important to achieve a multidisciplinary approach.
The population ageing is a reality associated with an increase in prevalence of Dementia. The use of benzodiazepines is often postulated as a risk factor in these syndromes.
Contrary to recommendations for its short-time use, long-term and chronic use are common, with an estimated 8,7% of elderly people in the US taking benzodiazepines.
Objectives
To clarify the most recent evidence on the use of benzodiazepines and the risk of developing dementia.
Methods
Non-systematic review of literature, using PubMed as database and filtering the results for meta-analysis.
Results
Four articles were included in this review.
Zhong G et al. concluded that risk of dementia increased in consumers of benzodiazepines and it was associated with higher doses.
In turn, AlDawasari A et al., when trying to clarify the use of different sedative-hypnotic drugs, found and increased risk with the consumption of benzodiazepines. After exclusion of articles with confounders and adjustment for protopathic bias, the risk was not maintained.
Lucchetta RC et al. concluded that the risk exists but without inferring differences between doses or duration of action.
Finally, Penninkilampi R e Eslick GD investigated this association, after controlling for the protopathic bias, concluding, contrary to AlDawasari et al., that the association benzodiazepines consumption and dementia do not result from this bias.
Conclusions
We cannot draw robust and concrete conclusions between benzodiazepines consumption and the pathogenesis of dementia because not only is the literature limited, but results are also heterogeneous.
However, these prescriptions must be carried out cautiously, especially in the elderly, due to the known adverse effects associated with them.
Sucrose yield in sugarcane is a complex process regulated by both environmental and endogenous factors. However, the metabolic balance driving vegetative growth and sucrose accumulation remains poorly understood. Herein, we carried out a comprehensive assessment of carbohydrate dynamics throughout the crop cycle in two sugarcane varieties varying in biomass production, evaluating the carbon metabolism in both leaves and stalks. Our data revealed that the decline in photosynthetic rates during sugarcane maturation is associated not only to accumulation of sugars in leaves but also due to stomatal and non-stomatal limitations. We found that metabolic processes in leaves and stalks were intrinsically linked. While IACSP94-2094 had higher stalk sucrose concentration than IACSP95-5000, this latter produced more biomass. Compared to IACSP95-5000, IACSP94-2094 showed higher sucrose phosphate synthase (SPS) activity in leaves and stalks, along with lower soluble acid invertase (SAI) activity in leaves during the maximum growth stage. Interestingly, IACSP94-2094 also exhibited higher stalk SPS activity and lower stalk SAI activity than IACSP95-5000 during maturation. High biomass production by IACSP95-5000 was associated with higher sucrose synthase (SuSy) and SAI activity in leaves and higher SuSy and soluble neutral invertase (SNI) activity in stalks when compared to IACSP94-2094 during the maximum growth. Despite the contrasting strategies, both varieties displayed similar total sucrose yield, a balance between sucrose concentration and biomass production. This phenomenon implies the presence of a compensatory mechanism in sugarcane, with high biomass production compensating low sucrose accumulation and vice versa.
Although the link between alcohol involvement and behavioral phenotypes (e.g. impulsivity, negative affect, executive function [EF]) is well-established, the directionality of these associations, specificity to stages of alcohol involvement, and extent of shared genetic liability remain unclear. We estimate longitudinal associations between transitions among alcohol milestones, behavioral phenotypes, and indices of genetic risk.
Methods
Data came from the Collaborative Study on the Genetics of Alcoholism (n = 3681; ages 11–36). Alcohol transitions (first: drink, intoxication, alcohol use disorder [AUD] symptom, AUD diagnosis), internalizing, and externalizing phenotypes came from the Semi-Structured Assessment for the Genetics of Alcoholism. EF was measured with the Tower of London and Visual Span Tasks. Polygenic scores (PGS) were computed for alcohol-related and behavioral phenotypes. Cox models estimated associations among PGS, behavior, and alcohol milestones.
Results
Externalizing phenotypes (e.g. conduct disorder symptoms) were associated with future initiation and drinking problems (hazard ratio (HR)⩾1.16). Internalizing (e.g. social anxiety) was associated with hazards for progression from first drink to severe AUD (HR⩾1.55). Initiation and AUD were associated with increased hazards for later depressive symptoms and suicidal ideation (HR⩾1.38), and initiation was associated with increased hazards for future conduct symptoms (HR = 1.60). EF was not associated with alcohol transitions. Drinks per week PGS was linked with increased hazards for alcohol transitions (HR⩾1.06). Problematic alcohol use PGS increased hazards for suicidal ideation (HR = 1.20).
Conclusions
Behavioral markers of addiction vulnerability precede and follow alcohol transitions, highlighting dynamic, bidirectional relationships between behavior and emerging addiction.
The UK Soft Drinks Industry Levy (SDIL) (announced in March 2016; implemented in April 2018) aims to incentivise reformulation of soft drinks to reduce added sugar levels. The SDIL has been applauded as a policy success, and it has survived calls from parliamentarians for it to be repealed. We aimed to explore parliamentary reaction to the SDIL following its announcement until two years post-implementation in order to understand how health policy can become established and resilient to opposition.
Design:
Searches of Hansard for parliamentary debate transcripts that discussed the SDIL retrieved 186 transcripts, with 160 included after screening. Five stages of Applied Thematic Analysis were conducted: familiarisation and creation of initial codebooks; independent second coding; codebook finalisation through team consensus; final coding of the dataset to the complete codebook; and theme finalisation through team consensus.
Setting:
The United Kingdom Parliament
Participants:
N/A
Results:
Between the announcement (16/03/2016) – royal assent (26/04/2017), two themes were identified 1: SDIL welcomed cross-party 2: SDIL a good start but not enough. Between royal assent – implementation (5/04/2018), one theme was identified 3: The SDIL worked – what next? The final theme identified from implementation until 16/03/2020 was 4: Moving on from the SDIL.
Conclusions:
After the announcement, the SDIL had cross-party support and was recognised to have encouraged reformulation prior to implementation. Lessons for governments indicate that the combination of cross-party support and a policy’s documented success in achieving its aim can help cement the resilience of it to opposition and threats of repeal.
The ability to quickly refresh gas-jet targets without cycling the vacuum chamber makes them a promising candidate for laser-accelerated ion experiments at high repetition rate. Here we present results from the first high repetition rate ion acceleration experiment on the VEGA-3 PW-class laser at CLPU. A near-critical density gas-jet target was produced by forcing a 1000 bar H$_2$ and He gas mix through bespoke supersonic shock nozzles. Proton energies up to 2 MeV were measured in the laser forward direction and 2.2 MeV transversally. He$^{2+}$ ions up to 5.8 MeV were also measured in the transverse direction. To help maintain a consistent gas density profile over many shots, nozzles were designed to produce a high-density shock at distances larger than 1 mm from the nozzle exit. We outline a procedure for optimizing the laser–gas interaction by translating the nozzle along the laser axis and using different nozzle materials. Several tens of laser interactions were performed with the same nozzle which demonstrates the potential usefulness of gas-jet targets as high repetition rate particle source.
White matter hyperintensity (WMH) burden is greater, has a frontal-temporal distribution, and is associated with proxies of exposure to repetitive head impacts (RHI) in former American football players. These findings suggest that in the context of RHI, WMH might have unique etiologies that extend beyond those of vascular risk factors and normal aging processes. The objective of this study was to evaluate the correlates of WMH in former elite American football players. We examined markers of amyloid, tau, neurodegeneration, inflammation, axonal injury, and vascular health and their relationships to WMH. A group of age-matched asymptomatic men without a history of RHI was included to determine the specificity of the relationships observed in the former football players.
Participants and Methods:
240 male participants aged 45-74 (60 unexposed asymptomatic men, 60 male former college football players, 120 male former professional football players) underwent semi-structured clinical interviews, magnetic resonance imaging (structural T1, T2 FLAIR, and diffusion tensor imaging), and lumbar puncture to collect cerebrospinal fluid (CSF) biomarkers as part of the DIAGNOSE CTE Research Project. Total WMH lesion volumes (TLV) were estimated using the Lesion Prediction Algorithm from the Lesion Segmentation Toolbox. Structural equation modeling, using Full-Information Maximum Likelihood (FIML) to account for missing values, examined the associations between log-TLV and the following variables: total cortical thickness, whole-brain average fractional anisotropy (FA), CSF amyloid ß42, CSF p-tau181, CSF sTREM2 (a marker of microglial activation), CSF neurofilament light (NfL), and the modified Framingham stroke risk profile (rFSRP). Covariates included age, race, education, APOE z4 carrier status, and evaluation site. Bootstrapped 95% confidence intervals assessed statistical significance. Models were performed separately for football players (college and professional players pooled; n=180) and the unexposed men (n=60). Due to differences in sample size, estimates were compared and were considered different if the percent change in the estimates exceeded 10%.
Results:
In the former football players (mean age=57.2, 34% Black, 29% APOE e4 carrier), reduced cortical thickness (B=-0.25, 95% CI [0.45, -0.08]), lower average FA (B=-0.27, 95% CI [-0.41, -.12]), higher p-tau181 (B=0.17, 95% CI [0.02, 0.43]), and higher rFSRP score (B=0.27, 95% CI [0.08, 0.42]) were associated with greater log-TLV. Compared to the unexposed men, substantial differences in estimates were observed for rFSRP (Bcontrol=0.02, Bfootball=0.27, 994% difference), average FA (Bcontrol=-0.03, Bfootball=-0.27, 802% difference), and p-tau181 (Bcontrol=-0.31, Bfootball=0.17, -155% difference). In the former football players, rFSRP showed a stronger positive association and average FA showed a stronger negative association with WMH compared to unexposed men. The effect of WMH on cortical thickness was similar between the two groups (Bcontrol=-0.27, Bfootball=-0.25, 7% difference).
Conclusions:
These results suggest that the risk factor and biological correlates of WMH differ between former American football players and asymptomatic individuals unexposed to RHI. In addition to vascular risk factors, white matter integrity on DTI showed a stronger relationship with WMH burden in the former football players. FLAIR WMH serves as a promising measure to further investigate the late multifactorial pathologies of RHI.
The current study evaluated alternative sources of nutrients to improve the soil fertility status and yield of maize-wheat succession in Southern Brazil. The treatments were: T1: no fertilization; T2: liming with dolomitic marble; T3: alternative liming (AL) with limestone interbedded with shale; T4: AL + 50% P - with Arad natural phosphate (P-ANP) + 50% P – triple superphosphate (P-TSP); T5: AL + 100% P-ANP; T6: AL + 100% P-ANP + 100% K-rich monzogranite; T7: AL + 100% P-ANP + 100% N (50% N from tung pressed cake (N-TPC) + 50% N-urea); T8: AL + 100% P-ANP + 100% K-rich monzogranite + 100% N (50% N-TPC + 50% N-Urea) + 100% S; T9: AL + regional average rate of NPK (5-20-20) formulation. Except for T7 and T8, all treatments received the full recommended rate of N through Urea. Immediate and residual effects were evaluated over 2.5 years (90, 360 and 900 days) on soil fertility and maize - wheat yield. The limestone interbedded with shale released Ca, Mg and corrected soil acidity similarly to dolomitic marble. The fertilization strategies used in T4, T7 and T8 presented the highest cumulative productivities while T3 (U$ = 1223), T9 (U$ = 1174) and T4 (U$ = 1122) resulted in higher profits than the other evaluated fertilization strategies. The limestone interbedded with shale (T3), alone or combined with 50% of P-ANP + 50% of P – TSP (T4) provided the best economical and technical results, highlighting the potential of selected alternative regional sources for soil fertility improvement and plant-nutrients supply.
We identify a set of essential recent advances in climate change research with high policy relevance, across natural and social sciences: (1) looming inevitability and implications of overshooting the 1.5°C warming limit, (2) urgent need for a rapid and managed fossil fuel phase-out, (3) challenges for scaling carbon dioxide removal, (4) uncertainties regarding the future contribution of natural carbon sinks, (5) intertwinedness of the crises of biodiversity loss and climate change, (6) compound events, (7) mountain glacier loss, (8) human immobility in the face of climate risks, (9) adaptation justice, and (10) just transitions in food systems.
Technical summary
The Intergovernmental Panel on Climate Change Assessment Reports provides the scientific foundation for international climate negotiations and constitutes an unmatched resource for researchers. However, the assessment cycles take multiple years. As a contribution to cross- and interdisciplinary understanding of climate change across diverse research communities, we have streamlined an annual process to identify and synthesize significant research advances. We collected input from experts on various fields using an online questionnaire and prioritized a set of 10 key research insights with high policy relevance. This year, we focus on: (1) the looming overshoot of the 1.5°C warming limit, (2) the urgency of fossil fuel phase-out, (3) challenges to scale-up carbon dioxide removal, (4) uncertainties regarding future natural carbon sinks, (5) the need for joint governance of biodiversity loss and climate change, (6) advances in understanding compound events, (7) accelerated mountain glacier loss, (8) human immobility amidst climate risks, (9) adaptation justice, and (10) just transitions in food systems. We present a succinct account of these insights, reflect on their policy implications, and offer an integrated set of policy-relevant messages. This science synthesis and science communication effort is also the basis for a policy report contributing to elevate climate science every year in time for the United Nations Climate Change Conference.
Social media summary
We highlight recent and policy-relevant advances in climate change research – with input from more than 200 experts.
Increasing emphasis on the use of real-world evidence (RWE) to support clinical policy and regulatory decision-making has led to a proliferation of guidance, advice, and frameworks from regulatory agencies, academia, professional societies, and industry. A broad spectrum of studies use real-world data (RWD) to produce RWE, ranging from randomized trials with outcomes assessed using RWD to fully observational studies. Yet, many proposals for generating RWE lack sufficient detail, and many analyses of RWD suffer from implausible assumptions, other methodological flaws, or inappropriate interpretations. The Causal Roadmap is an explicit, itemized, iterative process that guides investigators to prespecify study design and analysis plans; it addresses a wide range of guidance within a single framework. By supporting the transparent evaluation of causal assumptions and facilitating objective comparisons of design and analysis choices based on prespecified criteria, the Roadmap can help investigators to evaluate the quality of evidence that a given study is likely to produce, specify a study to generate high-quality RWE, and communicate effectively with regulatory agencies and other stakeholders. This paper aims to disseminate and extend the Causal Roadmap framework for use by clinical and translational researchers; three companion papers demonstrate applications of the Causal Roadmap for specific use cases.