Can the use of an auditory feedback device improve the gait pattern of paediatric patients with hemiparesis?

Postprint (published version

Analytical and graphical goodness of fit methods for parametric survival models with right-censored data

Validation of a parametric survival model is a very important but not straightforward task in the presence of censored data. In literature not much references are available about this topic, so in this project we collect and present some goodness of fit methods for parametric survival models when data present right-censored observations. These methods have been also implemented in R with the aim to create a local library with function for assess goodness of fit to right-censored data

New Formulations Loading Caspofungin for Topical Therapy of Vulvovaginal Candidiasis

This research was funded by the Spanish National Research Council (CSIC), project no. 202080E231, and the Agreement with the University of Barcelona and the University of Granada (Official State Gazette 311, on 27 November 2020).Vulvovaginal candidiasis (VVC) poses a significant problem worldwide affecting women from all strata of society. It is manifested as changes in vaginal discharge, irritation, itching and stinging sensation. Although most patients respond to topical treatment, there is still a need for increase the therapeutic arsenal due to resistances to anti-infective agents. The present study was designed to develop and characterize three hydrogels of chitosan (CTS), Poloxamer 407 (P407) and a combination of both containing 2% caspofungin (CSP) for the vaginal treatment of VVC. CTS was used by its mucoadhesive properties and P407 was used to exploit potential advantages related to increasing drug concentration in order to provide a local effect. The formulations were physically, mechanically and morphologically characterized. Drug release profile and ex vivo vaginal permeation studies were performed. Antifungal efficacy against different strains of Candida spp. was also evaluated. In addition, tolerance of formulations was studied by histological analysis. Results confirmed that CSP hydrogels could be proposed as promising candidates for the treatment of VVC.Spanish National Research Council (CSIC), project no. 202080E231Agreement with the University of Barcelona and the University of Granad

Improved detection and management of advanced HIV disease through a community adult TB‐contact tracing intervention with same‐day provision of the WHO‐recommended package of care including ART initiation in a rural district of Mozambique

Introduction: AIDS-mortality remains unacceptably high in sub-Saharan Africa, largely driven by advanced HIV disease (AHD). We nested a study in an existing tuberculosis (TB) contact-tracing intervention (Xpatial-TB). The aim was to assess the burden of AHD among high-risk people living with HIV (PLHIV) identified and to evaluate the provision of the WHO-recommended package of care to this population. Methods: All PLHIV ≥14 years old identified between June and December 2018 in Manhiça District by Xpatial-TB were offered to participate in the study if ART naïve or had suboptimal ART adherence. Consenting individuals were screened for AHD. Patients with AHD (CD4 < 200 cells/μL or WHO stage 3 or 4) were offered a package of interventions in a single visit, including testing for cryptococcal antigen (CrAg) and TB-lipoarabinomannan (TB-LAM), prophylaxis and treatment for opportunistic infections, adherence support or accelerated ART initiation. We collected information on follow-up visits carried out under routine programmatic conditions for six months. Results: A total of 2881 adults were identified in the Xpatial TB-contact intervention. Overall, 23% (673/2881) were HIV positive, including 351 TB index (64.2%) and 322 TB contacts (13.8%). Overall, 159/673 PLHIV (24%) were ART naïve or had suboptimal ART adherence, of whom 155 (97%, 124 TB index and 31 TB-contacts) consented to the study and were screened for AHD. Seventy percent of TB index-patients (87/124) and 16% of TB contacts (5/31) had CD4 < 200 cells/µL. Four (13%) of the TB contacts had TB, giving an overall AHD prevalence among TB contacts of 29% (9/31). Serum-CrAg was positive in 4.6% (4/87) of TB-index patients and in zero TB contacts. All ART naïve TB contacts without TB initiated ART within 48 hours of HIV diagnosis. Among TB cases, ART timing was tailored to the presence of TB and cryptococcosis. Six-month mortality was 21% among TB-index cases and zero in TB contacts. Conclusions: A TB contact-tracing outreach intervention identified undiagnosed HIV and AHD in TB patients and their contacts, undiagnosed cryptococcosis among TB patients, and resulted in an adequate provision of the WHO-recommended package of care in this rural Mozambican population. Same-day and accelerated ART initiation was feasible and safe in this population including among those with AHD

Differences In Adipose Tissue And Lean Mass Distribution In Patients With Collagen Vi Related Myopathies Are Associated With Disease Severity And Physical Ability

Mutations in human collagen VI genes cause a spectrum of musculoskeletal conditions in children and adults collectively termed collagen VI-related myopathies (COL6-RM) characterized by a varying degree of muscle weakness and joint contractures and which include Ullrich Congenital Muscular Dystrophy (UCMD) and Bethlem Myopathy (BM). Given that collagen VI is one of the most abundant extracellular matrix proteins in adipose tissue and its emerging role in energy metabolism we hypothesized that collagen VI deficiency might be associated with alterations in adipose tissue distribution and adipokines serum profile. We analyzed body composition by means of dual-energy X-ray absorptiometry in 30 pediatric and adult COL6-RM myopathy patients representing a range of severities (UCMD, intermediate-COL6-RM, and BM). We found a distinctive pattern of regional adipose tissue accumulation which was more evident in children at the most severe end of the spectrum. In particular, the accumulation of fat in the android region was a distinguishing feature of UCMD patients. In parallel, there was a decrease in lean mass compatible with a state of sarcopenia, particularly in ambulant children with an intermediate phenotype. All children and adult patients that were sarcopenic were also obese. These changes were significantly more pronounced in children with collagen VI deficiency than in children with Duchenne Muscular Dystrophy of the same ambulatory status. High molecular weight adiponectin and leptin were significantly increased in sera from children in the intermediate and BM group. Correlation analysis showed that the parameters of fat mass were negatively associated with motor function according to several validated outcome measures. In contrast, lean mass parameters correlated positively with physical performance and quality of life. Leptin and adiponectin circulating levels correlated positively with fat mass parameters and negatively with lean mass and thus may be relevant to the disease pathogenesis and as circulating markers. Taken together our results indicate that COL6-RM are characterized by specific changes in total fat mass and distribution which associate with disease severity, motor function, and quality of life and which are clinically meaningful and thus should be taken into consideration in the management of these patients

Differences in Adipose Tissue and Lean Mass Distribution in Patients with Collagen VI Related Myopathies Are Associated with Disease Severity and Physical Ability

Mutations in human collagen VI genes cause a spectrum of musculoskeletal conditions in children and adults collectively termed collagen VI-related myopathies (COL6-RM) characterized by a varying degree of muscle weakness and joint contractures and which include Ullrich Congenital Muscular Dystrophy (UCMD) and Bethlem Myopathy (BM). Given that collagen VI is one of the most abundant extracellular matrix proteins in adipose tissue and its emerging role in energy metabolism we hypothesized that collagen VI deficiency might be associated with alterations in adipose tissue distribution and adipokines serum profile. We analyzed body composition by means of dual-energy X-ray absorptiometry in 30 pediatric and adult COL6-RM myopathy patients representing a range of severities (UCMD, intermediate-COL6-RM, and BM). We found a distinctive pattern of regional adipose tissue accumulation which was more evident in children at the most severe end of the spectrum. In particular, the accumulation of fat in the android region was a distinguishing feature of UCMD patients. In parallel, there was a decrease in lean mass compatible with a state of sarcopenia, particularly in ambulant children with an intermediate phenotype. All children and adult patients that were sarcopenic were also obese. These changes were significantly more pronounced in children with collagen VI deficiency than in children with Duchenne Muscular Dystrophy of the same ambulatory status. High molecular weight adiponectin and leptin were significantly increased in sera from children in the intermediate and BM group. Correlation analysis showed that the parameters of fat mass were negatively associated with motor function according to several validated outcome measures. In contrast, lean mass parameters correlated positively with physical performance and quality of life. Leptin and adiponectin circulating levels correlated positively with fat mass parameters and negatively with lean mass and thus may be relevant to the disease pathogenesis and as circulating markers. Taken together our results indicate that COL6-RM are characterized by specific changes in total fat mass and distribution which associate with disease severity, motor function, and quality of life and which are clinically meaningful and thus should be taken into consideration in the management of these patients

Analytical and graphical goodness of fit methods for parametric survival models with right-censored data

Validation of a parametric survival model is a very important but not straightforward task in the presence of censored data. In literature not much references are available about this topic, so in this project we collect and present some goodness of fit methods for parametric survival models when data present right-censored observations. These methods have been also implemented in R with the aim to create a local library with function for assess goodness of fit to right-censored data

Demostracions de Gauss de la llei de reciprocitat quadràtica

A l'edat de 19 anys, Gauss aconseguí per primer cop demostrar la llei de la reciprocitat quadràtica, llei que havia restat 150 anys sense demostrar resistint-se als esforços de matemàtics importants com ara Fermat, Euler o Legendre. Aquest treball introdueix la llei de la reciprocitat quadràtica i mostra cinc de les vuit demostracions que donà Gauss d'aquesta llei.. El 8 d'abril de 1796 Gauss va trobar la primera demostració de la llei de reciprocitat quadràtica. Al llarg de la seva vida Gauss va donar-ne 8 demostracions diferents, i actualment es coneixen més de dues-centes demostracions d'aquest resultat de l'"aritmètica elemental".L'objectiu d'aquest treball és estudiar aquestes demostracions en les fonts originals, entendre-les bé i donar-ne exposicions el més clares i simples possible en el llenguatge de les matamàtiques actual

Demostracions de Gauss de la llei de reciprocitat quadràtica

A l'edat de 19 anys, Gauss aconseguí per primer cop demostrar la llei de la reciprocitat quadràtica, llei que havia restat 150 anys sense demostrar resistint-se als esforços de matemàtics importants com ara Fermat, Euler o Legendre. Aquest treball introdueix la llei de la reciprocitat quadràtica i mostra cinc de les vuit demostracions que donà Gauss d'aquesta llei.. El 8 d'abril de 1796 Gauss va trobar la primera demostració de la llei de reciprocitat quadràtica. Al llarg de la seva vida Gauss va donar-ne 8 demostracions diferents, i actualment es coneixen més de dues-centes demostracions d'aquest resultat de l'"aritmètica elemental".L'objectiu d'aquest treball és estudiar aquestes demostracions en les fonts originals, entendre-les bé i donar-ne exposicions el més clares i simples possible en el llenguatge de les matamàtiques actual

Analytical and graphical goodness of fit methods for parametric survival models with right-censored data

Validation of a parametric survival model is a very important but not straightforward task in the presence of censored data. In literature not much references are available about this topic, so in this project we collect and present some goodness of fit methods for parametric survival models when data present right-censored observations. These methods have been also implemented in R with the aim to create a local library with function for assess goodness of fit to right-censored data