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ObjectivePeople with human immunodeficiency virus (HIV) (PWH) have increased prevalence of multimorbidity and frailty at younger ages compared to the general population. This study investigated individual and combinatorial effects of neuropsychiatric and medical comorbidities as predictors of frailty in PWH.DesignAnalysis of data from the National NeuroAIDS Tissue Consortium, a longitudinal observational cohort.Methods524 PWH over age 40 were classified using Fried's Frailty criteria. Twelve comorbidities were documented from longitudinal data and associations between individual and co-occurring comorbidities with frailty were assessed using weighted network and logistic regression analyses.ResultsAt frailty assessment between 2015-2020, median age was 61 years, 76% were male, 94% were on ART, 73% had two or more comorbidities, 24% were frail, and 52% were prefrail. Among individual comorbidities, highest odds of frailty were in participants with depressive symptoms (adjusted odds ratio [aOR], 95% confidence interval [CI] 3.48 [2.22-5.46]]), followed by bone disease and COPD (2.47 [1.28-4.72] and 2.13 [1.36-3.34], respectively). Among co-occurring comorbidities, highest odds of frailty were in participants having depressive symptoms with diabetes, hypertension, or obesity (aORs [95% CIs] 5.29 [2.32-12.08], 5.21 [2.65-10.40], 4.85 [2.39-9.95], respectively), cognitive impairment with diabetes or renal disease, (2.81 [1.38-5.68] and 2.53 [1.26-5.03], respectively), renal disease with cardiovascular disease (2.81 [1.32-6.01]), and diabetes with obesity (2.76 [1.39-5.45]).ConclusionsCo-occurrence of depressive symptoms, cognitive impairment, diabetes, or renal disease with other medical conditions substantially increases odds of frailty in older PWH. Identifying and treating these comorbidities may help to reduce functional decline with aging in PWH.

Additional file 9: Supplementary Figure S6 – Full-length images of blots shown in Fig. 2c.

Additional file of Small RNA sequencing of extracellular vesicles identifies circulating miRNAs related to inflammation and oxidative stress in HIV patients

Additional file 1: Supplementary Figure S1: Comparison of total read counts for each RNA biotype in HIV-positive (n = 12) versus HIV-negative (n = 12) subjects. Supplementary Figure S2. Principal component analysis of the top 50 miRNAs identified by small RNA sequencing of plasma EV RNAs from HIV-positive (n = 12) and HIV-negative (n = 12) subjects. Three HIV-negative outliers (circled in green) were excluded from downstream differential expression analysis. Supplementary Figure S3. Plasma EV isolation and purification to exclude extravesicular RNAs. EV fractions were isolated from pooled plasma of healthy control subjects (n = 3) using the PureExo kit. Defibrinated plasma was either untreated, or treated with RNAse A, or with Proteinase-K followed by RNAse A, to eliminate extravesicular RNAs. TEM (top), particle size distribution (bottom left), particle concentration (bottom middle), and immunoblotting for exosome markers and ApoA1 (bottom right) are shown for each treatment condition. Supplementary Figure S4. Comparison of Cq values of miRNAs in plasma EVs of HIV-positive and HIV-negative subjects in the validation cohort, stratified by cocaine use. Mean and SEM are shown. Significance was calculated using Mann Whitney test. (n = 8 HIV-positive and n = 8 HIV-negative subjects). Supplementary Figure S5: Scatter plots showing inverse relationships between PUFA metabolites and EV-associated miRNAs. Pearson correlation coefficient and p-value are shown above each plot. n = 16 subjects (8 HIV-positive and 8 HIV-negative). DHA, docosahexaenoate (22:6n3); n3 DPA, docosapentaenoate (22:5n3); n6 DPA, docosapentaenoate (22:5n6) and EPA, eicosapentaenoate (20:5n3).

A software architect turns system requirements into a suitable software architecture through an architecture optimization process. However, how should the architect decide which quality improvement to prioritize, e.g., security or reliability? In software product line, should a small improvement in multiple products be preferred over a large improvement in a single product? Existing architecture optimization methods handle various steps in the process, but none of them systematically guides the architect in generating an optimal architecture from the initial requirements. In this work we present an end-to-end approach for generating an optimal software architecture for a single software product and an optimal family of architectures for a family of products. We report on a case-study of applying our approach to optimize five industry-grade products in a real-life product line architecture, where 359 possible combinations of ten different quality efforts were prioritized.

There is a gap between our ability to reuse high-level concepts in software design and our ability to reuse the code implementing them. Language Oriented Programming (LOP) is a software development paradigm that aims to close this gap, through extensive use of Domain Specific Languages (DSLs). With LOP, the high-level reusable concepts become reusable DSL constructs, and their translation into code level concepts is done in the DSL implementation. Particular products are implemented using DSL code, thus reusing only high-level concepts. In this paper we provide a comparison between two implementation approaches for LOP: (a) using external DSLs with a projectional language workbench (MPS); and (b) using internal DSLs with an LOP language (Cedalion). To demonstrate how reuse is achieved in each approach, we present a small case study, where LOP is used to build a Software Product Line (SPL) of calculator software.

Additional file 6: Figure S1. Depletion of abundant proteins from CSF. Figrue S2. Immunoblotting for ER membrane markers calnexin and Erp72, and exosome markers CD81 and CD9 in CSF EVs from 2 representative HIV+ subjects. Figure S3. Comparison of CSF EV concentrations and protein abundance in HIV+ non-HAND, ANI + MND, and HAD subjects. Figure S4. Unsupervised heatmap of 101 CSF EV proteins identified in 20 HIV+ subjects with (n = 10) and without (n = 10) HAND.

Article appendices, supplemental figures and tables.

Additional file 1: Figure S1. Overview and comparison of differentially expressed gene sets. (a) Number of differentially expressed genes from models contrasting HIV+ smokers vs. HIV- and HIV+ non-smokers and Venn diagrams of overlapping up- and down-regulated gene sets; (b) Number of differentially expressed genes from models contrasting HIV+ smokers vs. HIV- and HIV+ non-smokers in sensitivity analyses excluding HIV+ participants with HIV viral load > 200 and Venn diagrams of overlapping up- and down-regulated gene sets; (c) Venn diagrams comparing sets of up- and down-regulated genes in full cohort analyses vs. HIV viral load > 200 excluded cohort, with arrays from HIV- non-smokers as the reference; and (d) Venn diagrams comparing sets of up- and down-regulated genes in full cohort analyses vs. HIV viral load > 200 excluded cohort, with HIV+ nonsmokers as the reference. Genes with FDR-adjusted p value < 0.15, absolute log2 FC > 0.25 were deemed differentially expressed for all comparisons. Figure S2. Expression levels of genes associated with increased depressive symptoms stratified by HIV status, tobacco smoking, and CES-D score ≥ 16. Boxplots of normalized expression levels for genes associated with CES-D ≥ 16 in multivariate logistic regression models (Table 2). Values from five HIV- participants with CES-D ≥ 16 were excluded from plots for clarity. Horizontal bars denote medians, boxes span IQRs, whiskers extend to 1.5 x IQR. Dots denote expression values from individual arrays. Groups were compared using the Wilcoxon rank-sum test. Abbreviations: CES-D, Center for Epidemiological Studies Depression Scale; CES-D–, CES-D score < 16; CES-D16+, CES-D score ≥ 16; IQR, interquartile range; TS+, tobacco smoker; TS-, non-smoker. Figure S3. Expression levels of selected immune/interferon response, stress/chemical response, mitochondrion, and smoking-associated genes stratified by HIV status and marijuana or tobacco smoking. Boxplots of normalized gene expression levels for selected genes in Figure 4. Horizontal bars denote medians, boxes span IQRs, whiskers extend to 1.5 x IQR. Dots denote expression values from individual arrays. Groups were compared using the Wilcoxon rank-sum test. Abbreviations: IQR, interquartile range; MJ+, marijuana smoker; MJ-, marijuana non-smoker; TS+, tobacco smoker; TS-, non-smoker. Figure S4. Genes with high correlation to known smoking-associated gene SASH1 in HIV+ smokers and HIV- non-smokers. Correlation analyses of eight DE genes in HIV+ smokers vs. HIV- non-smokers showing significant correlation with SASH1 expression. Probe intensities were normalized and generalized-log2 transformed using the R/Bioconductor vsn package. Dots denote probe intensities from individual arrays, r denotes Pearson’s correlation coefficient, q denotes FDR-adjusted p value. Abbreviations: FDR, false-discovery rate; TS+, tobacco smoker; TS-, non-smoker. Figure S5. Identification of outlier samples by principal component analysis (PCA). Scatter plot of the first two principal components calculated from the set of 24,941 normalized probe intensities (n = 125 microarrays). Outlier samples removed from subsequent differential expression analyses are marked as red triangles (n = 6). Abbreviations: PC, principal component

Additional file 6: Figure S1. Depletion of abundant proteins from CSF. Figrue S2. Immunoblotting for ER membrane markers calnexin and Erp72, and exosome markers CD81 and CD9 in CSF EVs from 2 representative HIV+ subjects. Figure S3. Comparison of CSF EV concentrations and protein abundance in HIV+ non-HAND, ANI + MND, and HAD subjects. Figure S4. Unsupervised heatmap of 101 CSF EV proteins identified in 20 HIV+ subjects with (n = 10) and without (n = 10) HAND.

Additional file 1: Figure S1. Overview and comparison of differentially expressed gene sets. (a) Number of differentially expressed genes from models contrasting HIV+ smokers vs. HIV- and HIV+ non-smokers and Venn diagrams of overlapping up- and down-regulated gene sets; (b) Number of differentially expressed genes from models contrasting HIV+ smokers vs. HIV- and HIV+ non-smokers in sensitivity analyses excluding HIV+ participants with HIV viral load > 200 and Venn diagrams of overlapping up- and down-regulated gene sets; (c) Venn diagrams comparing sets of up- and down-regulated genes in full cohort analyses vs. HIV viral load > 200 excluded cohort, with arrays from HIV- non-smokers as the reference; and (d) Venn diagrams comparing sets of up- and down-regulated genes in full cohort analyses vs. HIV viral load > 200 excluded cohort, with HIV+ nonsmokers as the reference. Genes with FDR-adjusted p value < 0.15, absolute log2 FC > 0.25 were deemed differentially expressed for all comparisons. Figure S2. Expression levels of genes associated with increased depressive symptoms stratified by HIV status, tobacco smoking, and CES-D score ≥ 16. Boxplots of normalized expression levels for genes associated with CES-D ≥ 16 in multivariate logistic regression models (Table 2). Values from five HIV- participants with CES-D ≥ 16 were excluded from plots for clarity. Horizontal bars denote medians, boxes span IQRs, whiskers extend to 1.5 x IQR. Dots denote expression values from individual arrays. Groups were compared using the Wilcoxon rank-sum test. Abbreviations: CES-D, Center for Epidemiological Studies Depression Scale; CES-D–, CES-D score < 16; CES-D16+, CES-D score ≥ 16; IQR, interquartile range; TS+, tobacco smoker; TS-, non-smoker. Figure S3. Expression levels of selected immune/interferon response, stress/chemical response, mitochondrion, and smoking-associated genes stratified by HIV status and marijuana or tobacco smoking. Boxplots of normalized gene expression levels for selected genes in Figure 4. Horizontal bars denote medians, boxes span IQRs, whiskers extend to 1.5 x IQR. Dots denote expression values from individual arrays. Groups were compared using the Wilcoxon rank-sum test. Abbreviations: IQR, interquartile range; MJ+, marijuana smoker; MJ-, marijuana non-smoker; TS+, tobacco smoker; TS-, non-smoker. Figure S4. Genes with high correlation to known smoking-associated gene SASH1 in HIV+ smokers and HIV- non-smokers. Correlation analyses of eight DE genes in HIV+ smokers vs. HIV- non-smokers showing significant correlation with SASH1 expression. Probe intensities were normalized and generalized-log2 transformed using the R/Bioconductor vsn package. Dots denote probe intensities from individual arrays, r denotes Pearson’s correlation coefficient, q denotes FDR-adjusted p value. Abbreviations: FDR, false-discovery rate; TS+, tobacco smoker; TS-, non-smoker. Figure S5. Identification of outlier samples by principal component analysis (PCA). Scatter plot of the first two principal components calculated from the set of 24,941 normalized probe intensities (n = 125 microarrays). Outlier samples removed from subsequent differential expression analyses are marked as red triangles (n = 6). Abbreviations: PC, principal component

Article appendices, supplemental figures and tables.

Article appendices, supplemental figures and tables.

Aquesta recerca pretén treballar la guerra antipartisana a Espanya des de l’inici de la Guerra Civil fins a la derrota definitiva de la resistència armada republicana en 1952. Des d’un enfocament de la història sociocultural de la guerra s’analitzaran les estratègies militars, així com els objectius, els resultats i les conseqüències de la lluita contrainsurgent. En aquest sentit, s’aportaran nous continguts i anàlisis al marc interpretatiu que sosté que la Guerra Civil no va finalitzar l’abril de 1939, sinó que es va mantenir oberta dins de la postguerra i fins a 1952 a través d’una guerra asimètrica i de baixa intensitat. D’altra banda, s’abordarà en profunditat l’experiència de guerra dels guàrdies civils, soldats i altres forces auxiliars que van participar en la lluita contra les guerrilles republicanes. A més, la recerca pretén inserir la guerra antipartisana a Espanya dins del cicle de guerres irregulars que es van experimentar durant la Segona Guerra Mundial. Per a això, s’ha fet un exhaustiu treball de localització, consulta i anàlisi de fonts documentals, moltes d’elles inèdites, així com de les referències bibliogràfiques més solvents sobre aquestes qüestions. Esta investigación pretende abordar la guerra antipartisana en España desde el inicio de la Guerra Civil hasta la derrota definitiva de la resistencia armada republicana en 1952. Desde un enfoque de la historia sociocultural de la guerra se analizarán las estrategias militares, así como los objetivos, los resultados y las consecuencias de la lucha contrainsurgente. En este sentido, se aportarán nuevos contenidos y análisis al marco interpretativo que sostiene que la Guerra Civil no finalizó en abril de 1939, sino que se mantuvo abierta dentro de la posguerra y hasta 1952 a través de una guerra asimétrica y de baja intensidad. Por otra parte, se abordará en profundidad la experiencia de guerra de los guardias civiles, soldados y otras fuerzas auxiliares que participaron en la lucha contra las guerrillas republicanas. Además, la investigación buscará insertar la guerra antipartisana en España dentro del ciclo de guerras irregulares que se experimentaron al calor de la Segunda Guerra Mundial. Para ello, se ha realizado un exhaustivo trabajo de localización, consulta y análisis de fuentes documentales, muchas de ellas inéditas, así como de las referencias bibliográficas más solventes sobre estas cuestiones. The topic of this PhD thesis is the anti-partisan war in Spain from the beginning of the Civil War in 1936 until Republican armed resistance was definitively quashed in 1952. Military strategies and the objectives, outcomes and consequences of the counterinsurgent fight will be analysed from the perspective of the sociocultural history of war. In this regard, this thesis contributes new information and analysis to the interpretation which holds that the Spanish Civil War did not end in April 1939, but rather continued during the subsequent post-war period, and until 1952, as an asymmetric and low-intensity conflict. Moreover, the war experience of civil guards, soldiers and other auxiliary forces who participated in the fight against Republican guerrillas will be discussed in depth. Furthermore, this research aims to situate the anti-partisan war in Spain within the cycle of irregular wars which occurred in the context of the Second World War. This thesis is the result of a thorough research process which involved locating, consulting and analysing documentary sources, many of them unpublished, as well as relevant bibliographical sources. Universitat Autònoma de Barcelona. Programa de Doctorat en Història Comparada, Política i Social

Abans de tractar la pròpia batalla de Stalingrad en si, he intentat fer veure al lector els seus precedents. Els anys anteriors, amb les victòries al Front Occidental, es pot veure com el concepte de batalla decisiva està present en gairebé totes les operacions. Seguint cronològicament el tema era necessari citar com l’Operació Barba-roja, per la invasió i derrota de la Unió Soviètica, basada en tres eixos d’avenç i el posterior assalt sobre Moscou varen fer que els alemanys es veiessin obligats a buscar unes solucions que poc tenien a veure amb la teoria militar que havien seguit fins aleshores i que havia marcat la seva línia d’actuació. I és que la capacitat bèl·lica de la Unió Soviètica, el terreny i les limitacions logístiques varen fer que les operacions de l’any 1942, on sempre ha destacat Stalingrad, haguessin de seguir unes normes de guerra molt diferents de les fins aleshores vistes. El treball també tracta la pròpia batalla de Stalingrad i les conseqüències d’aquesta. Aquest consta d’un dens apartat on la informació requereix una acurada citació dels autors que han pogut accedir a les fonts primàries del conflicte, ja que aquests documents són essencials per entendre la derrota nacionalsocialista i el triomf soviètic. Però el més important d’aquesta secció és el tractament de l’impacte que té la batalla en diferents àmbits socioculturals, des de la cinematografia passant per la cultura, l’art i la memòria col·lectiva. .

En el transcurs dels segles les diverses societats han reproduït sistemes d’opressió envers les dones, sistemes patriarcals que han tingut les seves manifestacions en tots els àmbits de la vida quotidiana, construint un discurs misogin que es manifesta en forma de discriminacions arribant fins a l’anomenada violència contra la dona. Tot i això, gràcies a la resposta organitzada que ha sorgit en els últims anys des del feminisme, diverses autores, col·lectius i associacions han detectat la presència d’aquesta tipologia de violència en l’àmbit de la salut, i més oncretament al llarg dels processos reproductius naturals de les dones. Aquesta és anomenada violència obstètrica, i ha estat definida com: l'apropiació del cos i dels processos reproductius de les dones per prestadors de salut, que s'expressa en un tracte jeràrquic deshumanitzador, en un abús que s’observa en la medicalització i patologització dels processos naturals, portant amb si la pèrdua d'autonomia i la capacitat per decidir lliurement sobre els seus cossos i sexualitat i impactant negativament en la qualitat de vida de les dones ( El parto es nuestro, 2020) . Malauradament, encara que aquesta praxi hagi estat estudiada des de les diverses ciències socials com l’antropologia, la psicologia i la sociologia, no ha estat reconeguda per aquelles que l’exerceixen, les ciències de la salut. Així doncs, la violència obstètrica se segueix practicant diàriament en els centres de salut, vulnerant els drets humans i sexuals de les dones. Mentre que al mateix temps no existeix cap mena de regla que penalitzi l’agressor/-a, ni per altra banda cap mena de recurs, suport i/o acompanyament per la persona que pateix aquestes atroces praxis. Per tant, entre les motivacions per realitzar la present investigació caldria esmentar la situació expressada anteriorment, juntament amb la impotència que em desperta com a futura treballadora social, a la por que em genera poder viure com a dona el dia de demà aquesta mala experiència, i al meu interès al llarg dels anys per la salut sexual i reproductiva. Així doncs, em proposo dur a terme una exploració teòrica amb l’objectiu general d’analitzar la problemàtica social definida com a violència obstètrica, així com la intervenció que es pot realitzar des de l’àmbit social, concretament en el camp del treball social sanitari.

El present escrit tracte sobre la vulneració dels drets de les persones retingudes en els centres d’internament d'estrangers (CIEs). En els últims anys l’estat espanyol ha rebut a moltes persones en situació regular procedents d’altres països, ja sigui per contractes de treball, reagrupació familiar o per visat (turista, estudiant...). Però a més, també han arribat col·lectius sense els permisos necessaris per poder establir una residència a l'estat espanyol. En el moment que aquestes persones resideixen de forma irregular en el país, existeix la possibilitat que siguin detingudes pels agents de les forces de seguretat i com a conseqüència acabin deportades al seu país de procedència. No obstant això, prèviament són portades el centre d'internament d'estrangers (CIE). Aquest Treball de Fi de Grau (TFG) es centrarà en el procés que es duu a terme des del moment que les autoritats detenen a la persona fins que aquesta és internada i surt del CIE, fonamentalment per demostrar com es vulneren els seus drets. El fet de no disposar de la documentació necessària fa que l'estat els privi de la seva llibertat amb l'ingrés en un CIE, i no només això, sinó que un cop allà dins es vulneren els seus drets i no es respecta el dret a la dignitat. Per això el paper dels treballadors/es socials en aquesta problemàtica és molt important, atès que una de les nostres tasques com a professionals és vetllar pels drets de les persones vulnerables. En aquest sentit hem de fer front a aquestes injustícies i visualitzar-les per poder garantir un canvi social i de consciència davant aquestes realitats, a més de promoure el benestar dels interns. Així doncs, aquest TFG també plantejarà algunes propostes en aquest sentit.