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Background and objectivesIn Italy, approximately 650 individuals receive a diagnosis of primary progressive aphasia (PPA) every year. Unfortunately, the frequency with which patients are referred to speech-language services is suboptimal, likely due to skepticism regarding the value of speech-language therapy in the context of neurodegeneration.Materials and methodsWe conducted a virtual survey of speech and language therapists (SLTs) across Italy, to collect information about the assessment, intervention and management of patients with PPA. To ensure that as many SLTs as possible received the survey, the Italian Federation of SLTs (Federazione Logopedisti Italiani, FLI) aided in disseminating the survey.ResultsIn total, 336 respondents participated in the online survey, 140 of whom had previous experience with PPA patients. Respondents indicated having seen a total of 428 PPA patients in the previous 24 months (three patients on average, range: 0-40). SLTs who reported never working with PPA identified underdiagnoses, low referral rates and the rarity of the clinical syndrome as major reasons for their lack of experience with PPA. SLTs with experience working with PPA indicated that patients may not have accessed services because of service dysfunction and geographical barriers. Respondents reported using informal interviews during assessments and tests developed for post-stroke aphasia, while impairment-based/restitutive interventions were utilised most often.ConclusionFindings may serve to inform health policy organisations regarding the current shortcomings and needed recommendations for improving the care of individuals with PPA in Italy. Improving awareness of the utility of rehabilitation among SLTs and other clinical service providers may serve to facilitate access to intervention, which in turn will serve to better support individuals living with PPA.What this paper addsWhat is already known on the subject Speech and language therapists (SLTs) play a crucial role in the assessment, diagnosis and treatment of people with primary progressive aphasia (PPA). However, the frequency with which individuals with PPA are referred for speech and language services is suboptimal due to skepticism regarding the value of speech and language therapy in the context of neurodegeneration, the scarcity of SLTs with expertise in the treatment of PPA and the lack of awareness of the SLT role amongst referrers. What this paper adds to existing knowledge In recognition of the lack of published information on the provision of speech and language therapy services and clinicians' approaches to the assessment and treatment of individuals with PPA in Italy, we conducted an online survey to evaluate the current referral patterns for speech and language therapy services and to examine the current barriers to access these services for individuals with PPA in Italy. What are the potential or actual clinical implications of this work? The data presented here support that SLTs view treatment as useful for individuals with PPA and other professional figures and may serve to improve access to intervention, which in turn will serve to better support individuals living with PPA. The results highlight the need to inform health policy organisations about current gaps and aid in developing recommendations for improving the care of individuals with PPA, in order to understand how SLTs can best support individuals with PPA and their families.

Summary: Background: Sex and gender inequalities in ischemic heart diseases persist. Although ischemic heart disease is less common in women, they experience worse clinical outcomes and are less likely to receive guideline-recommended treatments. The primary scientific literature from which clinical guideline recommendations are derived may not have considered potential sex- and gender biases. This study aims to determine whether the literature cited in recent cardiovascular guidelines’ clinical recommendations contain sex and gender biases. Methods: We analysed publications cited in the 2019 European Society of Cardiology (ESC) guideline recommendations on chronic coronary syndromes, using a checklist to guide data extraction and evaluate the individual studies for sex- and gender-related aspects, such as inclusion/exclusion criteria, outcome measures, and demographic data reporting. To assess representation over time, the proportion of women participants in each study was computed and analysed using a beta regression model. We also examined the associations between women’s representation, journal impact factor and author gender. Findings: Among the 20 ESC recommendations on chronic coronary syndromes, four contained sex-related statements; we did not identify any gender-specific suggestions. The referenced literature upon which these recommendations were based consisted of 108 articles published between 1991 and 2019, encompassing more than 1.6 million study participants (26.8%; 432,284 women). Only three studies incorporated sex-sensitive designs; none were gender-specific. The term “gender” did not occur in 84% (n = 91/108) of the publications; when used, it was exclusively to denote biological sex. The proportion of women (assumed by investigators) among study participants fluctuated over time. Having a woman as first (odds ratio (OR) = 1.68, 95% CI: 1.19–2.39) or last author (OR = 2.28, 95% CI: 1.31–3.97), was significantly associated with having more women participants in the study. Interpretation: The data underlying ESC guideline recommendations largely lack reporting of possible sex- and gender-specific aspects, and women are distinctly underrepresented. To what extent these recommendations apply to members of specific population groups who are not well-represented in the underlying evidence base remains unknown. Funding: This study is part of the Gender and Health Inequalities (GENDHI) project, ERC-2019-SyG. This project has received funding from the European Research Council (ERC).

Abstract Cranial reconstructions are essential for restoring both function and aesthetics in patients with craniofacial deformities or traumatic injuries. Titanium prostheses have gained popularity due to their biocompatibility, strength, and corrosion resistance. The use of Superplastic Forming (SPF) and Single Point Incremental Forming (SPIF) techniques to create titanium prostheses, specifically designed for cranial reconstructions was investigated in an ovine model through microtomographic and histomorphometric analyses. The results obtained from the explanted specimens revealed significant variations in bone volume, trabecular thickness, spacing, and number across different regions of interest (VOIs or ROIs). Those regions next to the center of the cranial defect exhibited the most immature bone, characterized by higher porosity, decreased trabecular thickness, and wider trabecular spacing. Dynamic histomorphometry demonstrated differences in the mineralizing surface to bone surface ratio (MS/BS) and mineral apposition rate (MAR) depending on the timing of fluorochrome administration. A layer of connective tissue separated the prosthesis and the bone tissue. Overall, the study provided validation for the use of cranial prostheses made using SPF and SPIF techniques, offering insights into the processes of bone formation and remodeling in the implanted ovine model.

The present work collects some results of the three-years Research Program “BioForming“, funded by the Italian Ministry of Education (MIUR) and aimed to investigate the possibility of using flexible sheet forming processes, i.e. Super Plastic Forming (SPF) and Single Point Incremental Forming (SPIF), for the manufacturing of patient-oriented titanium prostheses. The prosthetic implants used as case studies were from the skull; in particular, two different Ti alloys and geometries were considered: one to be produced in Ti-Gr23 by SPF and one to be produced in Ti-Gr2 by SPIF. Numerical simulations implementing material behaviours evaluated by characterization tests were conducted in order to design both the manufacturing processes. Subsequently, experimental tests were carried out implementing numerical results in terms of: (i) gas pressure profile able to determine a constant (and optimal) strain rate during the SPF process; (ii) tool path able to avoid rupture during the SPIF process. Post forming characteristics of the prostheses in terms of thickness distributions were measured and compared to data from simulations for validation purposes. A good correlation between numerical and experimental thickness distributions has been obtained; in addition, the possibility of successfully adopting both the SPF and the SPIF processes for the manufacturing of prostheses has been demonstrated.

ObjectivesDepression is a major contributor of young people's burden of disease. In this study we aim to estimate the effect of elevated depressive symptoms on physical health-related quality of life.DesignWe used self-reported information from the prospective BELLA cohort study, which included adolescents selected from the general population in Germany. The baseline assessment (2003–2006) and the 1-, 2-, and 6-year follow-up waves provide the data basis.ParticipantsThe baseline study population consisted of 1,460 adolescents between the ages of 12 and 17 who, according to their caregivers, did not suffer from depression.VariablesThe primary outcome, as measured by the physical component score (PCS) of the SF-36 at a 6-year follow-up (range: 0–100), is physical health-related quality of life. The exposure of interest is depressive symptoms, as measured by the Center for Epidemiological Studies Depression Scale for Children (CES-DC) at baseline, 1-year follow-up and 2-year follow-ups (range: 0–60). We dichotomized the exposure into subthreshold (≤15) and elevated depressive symptoms (>15). For the main analyses we considered a cumulative index for elevated depressive symptoms across the three time points (range: 0–3). Considered confounders are sex, age, socioeconomic status, migrant background, social support, anxiety symptoms, physical activity, chronic diseases, and sleeping problems.Statistical methodsWe used multiple imputation to account for missing values. Within each imputed dataset, we applied inverse probability weighting (IPW) to estimate the effect of the cumulative index for elevated depressive symptoms at baseline, 1- and 2-year follow-up on physical health-related quality of life at 6-year follow-up. We derived 95% confidence intervals by bootstrapping.ResultsAfter adjusting with IPW, the effect of the cumulative index per one unit increase of elevated depressive symptoms on the physical component score was −1.71 (95% CI: −3.51 to −0.04). The adjusted effect estimates of single exposure of elevated depressive symptoms on physical health-related quality of life were −0.83 (95% CI: −3.69 to 1.87) at baseline, −2.96 (95% CI: −4.94 to −0.52) at 1-year follow-up and −1.32 (95% CI: −3.85 to 1.15) at 2-year follow-up.ConclusionFindings suggest that elevated depressive symptoms during adolescence decrease physical health-related quality of life in young adulthood.

Abstract Background Machine learning models promise to support diagnostic predictions, but may not perform well in new settings. Selecting the best model for a new setting without available data is challenging. We aimed to investigate the transportability by calibration and discrimination of prediction models for cognitive impairment in simulated external settings with different distributions of demographic and clinical characteristics. Methods We mapped and quantified relationships between variables associated with cognitive impairment using causal graphs, structural equation models, and data from the ADNI study. These estimates were then used to generate datasets and evaluate prediction models with different sets of predictors. We measured transportability to external settings under guided interventions on age, APOE ε4, and tau-protein, using performance differences between internal and external settings measured by calibration metrics and area under the receiver operating curve (AUC). Results Calibration differences indicated that models predicting with causes of the outcome were more transportable than those predicting with consequences. AUC differences indicated inconsistent trends of transportability between the different external settings. Models predicting with consequences tended to show higher AUC in the external settings compared to internal settings, while models predicting with parents or all variables showed similar AUC. Conclusions We demonstrated with a practical prediction task example that predicting with causes of the outcome results in better transportability compared to anti-causal predictions when considering calibration differences. We conclude that calibration performance is crucial when assessing model transportability to external settings.

Abstract Background Migraine is a very common headache disorder on the population level, characterized by symptomatic attacks (activity). For many people with migraine, the migraine symptoms intermittently or permanently cease during their lifetime (inactive migraine). The current diagnostic classification of migraine considers two states: active migraine (having migraine symptoms within the last year) and not having active migraine (including both individuals with inactive migraine and those who never had migraine). Defining a state of inactive migraine that has gone into remission may better capture the trajectories of migraine across the lifespan and contribute to a better understanding of its biological processes. We aimed to quantify the prevalence of never, active, and inactive migraine separately, using modern prevalence and incidence estimation methodology to better describe the complexity of migraine trajectories at the population level. Methods Using a multistate modeling approach, data from the Global Burden of Disease (GBD) study, and results from a population-based study, we estimated the transition rates by which individuals moved between migraine disease states and estimated prevalences of never, active and inactive migraine. We used data from the GBD project and a hypothetical cohort of 100,000 people with a starting age of 30 and 30 years of follow-up, both in Germany and globally, stratified by sex. Results In Germany, the estimated rate of transition from active to inactive migraine (remission rate) increased after the age of 22.5 in women and 27.5 in men. The pattern for men in Germany was similar to the one observed on the global level. The prevalence of inactive migraine among women reaches 25.7% in Germany and 16.5% globally at age 60. For men, the inactive migraine prevalence estimates at the same age were 10.4% in Germany and 7.1% globally. Conclusions Considering an inactive migraine state explicitly reflects a different epidemiological picture of migraine across the lifecourse. We have demonstrated that many women of older ages may be in an inactive migraine state. Many pressing research questions can only be answered if population-based cohort studies collect information not only on active migraine but also on inactive migraine states.

BackgroundNeurological disorders are increasingly recognised as major causes of death and disability worldwide. The aim of this analysis from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2016 is to provide the most comprehensive and up-to-date estimates of the global, regional, and national burden from neurological disorders.MethodsWe estimated prevalence, incidence, deaths, and disability-adjusted life-years (DALYs; the sum of years of life lost [YLLs] and years lived with disability [YLDs]) by age and sex for 15 neurological disorder categories (tetanus, meningitis, encephalitis, stroke, brain and other CNS cancers, traumatic brain injury, spinal cord injury, Alzheimer's disease and other dementias, Parkinson's disease, multiple sclerosis, motor neuron diseases, idiopathic epilepsy, migraine, tension-type headache, and a residual category for other less common neurological disorders) in 195 countries from 1990 to 2016. DisMod-MR 2.1, a Bayesian meta-regression tool, was the main method of estimation of prevalence and incidence, and the Cause of Death Ensemble model (CODEm) was used for mortality estimation. We quantified the contribution of 84 risks and combinations of risk to the disease estimates for the 15 neurological disorder categories using the GBD comparative risk assessment approach.FindingsGlobally, in 2016, neurological disorders were the leading cause of DALYs (276 million [95% UI 247-308]) and second leading cause of deaths (9·0 million [8·8-9·4]). The absolute number of deaths and DALYs from all neurological disorders combined increased (deaths by 39% [34-44] and DALYs by 15% [9-21]) whereas their age-standardised rates decreased (deaths by 28% [26-30] and DALYs by 27% [24-31]) between 1990 and 2016. The only neurological disorders that had a decrease in rates and absolute numbers of deaths and DALYs were tetanus, meningitis, and encephalitis. The four largest contributors of neurological DALYs were stroke (42·2% [38·6-46·1]), migraine (16·3% [11·7-20·8]), Alzheimer's and other dementias (10·4% [9·0-12·1]), and meningitis (7·9% [6·6-10·4]). For the combined neurological disorders, age-standardised DALY rates were significantly higher in males than in females (male-to-female ratio 1·12 [1·05-1·20]), but migraine, multiple sclerosis, and tension-type headache were more common and caused more burden in females, with male-to-female ratios of less than 0·7. The 84 risks quantified in GBD explain less than 10% of neurological disorder DALY burdens, except stroke, for which 88·8% (86·5-90·9) of DALYs are attributable to risk factors, and to a lesser extent Alzheimer's disease and other dementias (22·3% [11·8-35·1] of DALYs are risk attributable) and idiopathic epilepsy (14·1% [10·8-17·5] of DALYs are risk attributable).InterpretationGlobally, the burden of neurological disorders, as measured by the absolute number of DALYs, continues to increase. As populations are growing and ageing, and the prevalence of major disabling neurological disorders steeply increases with age, governments will face increasing demand for treatment, rehabilitation, and support services for neurological disorders. The scarcity of established modifiable risks for most of the neurological burden demonstrates that new knowledge is required to develop effective prevention and treatment strategies.FundingBill & Melinda Gates Foundation.

The reshaping of End-of-Life (EoL) components by means of the sheet metal forming process has been considered largely attractive, even from the social and economic point of view. At the same time, EoL parts can often be characterized by non-uniform thicknesses or alternation of work-hardened/undeformed zones as the result of the manufacturing process. Such heterogeneity can hinder a proper reshaping of the EoL part, and residual marks on the reformed blanks can still be present at the end of the reshaping step. In a previous analysis, the authors evaluated the effectiveness of reshaping a blank with a deep-drawn feature by means of the Sheet Hydroforming (SHF) process: it was demonstrated that residual marks were still present if the deep-drawn feature was located in a region not enough strained during the reshaping step. Starting from this condition and adopting a numerical approach, additional investigations were carried out, changing the profile of the load applied by the blank holder and the maximum oil pressure. Numerical results were collected in terms of overall strain severity and residual height of the residual marks from the deep-drawn feature at the end of the reshaping step. Data were then fitted by accurate Response Surfaces trained by means of interpolant Radial Basis Functions and anisotropic Kriging algorithms, subsequently used to carry out a virtual optimization managed by multi-objective evolutionary algorithms (MOGA-II and NSGA-II). Optimization results, subsequently validated via experimental trials, provided the optimal working conditions to achieve a remarkable reduction of the marks from the deep-drawn feature without the occurrence of rupture. [ABSTRACT FROM AUTHOR]

Magnesium and its alloys represent promising candidates for biomedical implants due to their biodegradability and mechanical properties, which are similar to natural bone. However, their rapid degradation process characterized by dynamic pH fluctuations and significant hydrogen gas evolution during biocorrosion adversely affects both in vitro and in vivo assessments. While the ISO 10993-5 and 12 standards provide guidelines for evaluating the in vitro biocompatibility of biodegradable materials, they also introduce testing variability conditions that yield inconsistent results. To address these inherent characteristics of Mg alloys, developing improved methods that accurately simulate the physiological environment for in vitro biocompatibility testing is essential. This study introduces two novel extraction approaches for evaluating Mg alloys: a buffered solution utilizing PBS/DMEM with quaternary dilutions and a modified ISO standard protocol employing decuple dilution of conventional unbuffered extracts. The present findings establish that controlled optimization of extraction conditions, specifically buffer composition and dilution parameters, enables reliable in vitro cytotoxicity assessment of Mg alloys, providing a robust methodology that advances the preclinical evaluation of these promising biodegradable materials. [ABSTRACT FROM AUTHOR]