Abstract: Spiking neural networks (SNNs) using time-to-first-spike (TTFS) codes, in which neurons fire at most once, are appealing for rapid and low power processing. In this theoretical paper, we focus on information coding and decoding in those networks, and introduce a new unifying mathematical framework that allows the comparison of various coding schemes. In an early proposal, called rankorder coding (ROC), neurons are maximally activated when inputs arrive in the order of their synaptic weights, thanks to a shunting inhibition mechanism that progressively desensitizes the neurons as spikes arrive. In another proposal, called NoM coding, only the first N spikes of M input neurons are propagated, and these ``first spike patterns'' can be readout by downstream neurons with homogeneous weights and no desensitization: as a result, the exact order between the first spikes does not matter. This paper also introduces a third option - ""Ranked-NoM"" (R-NoM), which combines features from both ROC and NoM coding schemes: only the first N input spikes are propagated, but their order is readout by downstream neurons thanks to inhomogeneous weights and linear desensitization. The unifying mathematical framework allows the three codes to be compared in terms of discriminability, which measures to what extent a neuron responds more strongly to its preferred input spike pattern than to random patterns. This discriminability turns out to be much higher for RNoM than for the other codes, especially in the early phase of the responses. We also argue that RNoM is much more hardware-friendly than the original ROC proposal, although NoM remains the easiest to implement in hardware because it only requires binary synapses. Resumen: Las redes neuronales de picos o potenciales de acciôn (SNN) que utilizan códigos de tiempo hasta el primer pico (TTFS), en los que las neuronas se disparan una vez como máximo, son atractivas para un procesamiento rápido y de baja potencia. En este artículo teórico, nos enfocamos en la codificación y decodificación de información en esas redes, e introducimos un nuevo marco matemático unificador que permite la comparación de varios esquemas de codificación. En una propuesta inicial, llamada codificación por orden de rango (ROC), las neuronas se activan al máximo cuando las entradas llegan en el orden de sus pesos sinápticos, gracias a un mecanismo de inhibición de derivación que insensibiliza progresivamente las neuronas a medida que llegan los picos. En otra propuesta, denominada codificación NoM, solo se propagan los primeros N picos de las M neuronas de entrada, y estos ""primeros patrones de picos"" pueden ser leídos por las ""downstream neurons"" con pesos homogéneos y sin desensibilización: como resultado, el orden exacto entre los primeros picos no importa. Este documento también presenta una tercera opción: ""Ranked-NoM"" (R-NoM), que combina características de los esquemas de codificación ROC y NoM: solo se propagan los primeros picos de entrada N, pero las neuronas posteriores leen su orden gracias a pesos no homogéneos y desensibilización lineal. El marco matemático unificador permite comparar los tres códigos en términos de discriminabilidad, que mide en qué medida una neurona responde con más fuerza a su patrón de picos de entrada preferido que a patrones aleatorios. Esta discriminabilidad resulta ser mucho mayor para R-NoM que para los otros códigos, especialmente en la fase temprana de las respuestas. También argumentamos que R-NoM es mucho más compatible con el hardware que la propuesta ROC original, aunque NoM sigue siendo el más fácil de implementar en hardware porque solo requiere sinapsis binarias.

Abstract: Background: Deep brain stimulation (DBS) surgery is a treatment in the advanced stage of Parkinson's disease (PD). Despite close follow-up, multiple evaluations, and several months of timeconsuming programming sessions, the clinical response may not be optimal in some cases. Imageguided programming (I-GP) could help optimize programming sessions with better clinical outcomes. Objective: To evaluate clinical and quality of life (QoL) outcomes with I-GP in PD patients with DBS of the subthalamic nucleus (STN) and suboptimal clinical improvement and refractory symptoms to conventional clinical programming. Methods: A prospective study in 16 patients with a diagnosis of PD with STN-DBS and remaining adverse effects or symptoms despite a clinical programming adjustment. We simulate potentially effective stimulation based on volume tissue activated (VTA) using commercially available software tools. Clinical outcomes were assessed with motor and quality of life scales. Results: The most frequent suboptimal symptom was gait disorder 33.3% (n=9), residual motor symptoms 25.9%(n=7), and speech 25.9%(n=7). Statistically significant results (p=0.001) were found after I-GP with change in the global Deep Brain Stimulation – Impairment score (41%), The 8- item version of the Parkinson's Disease Questionnaire (47%), EuroQol visual analogue scale (62%), and motor scale (24%). Conclusions: In suboptimal cases of patients with PD and STN-DBS, especially with ongoing and residual motor symptoms, I-GP could be useful to optimize the programming of DBS and improve patients' QoL.

Abstract: Context: Whether due to geopolitical instability, as in Colombia or Venezuela, global warming, or simply tourism, the movement of lowlanders to high altitudes is increasing. This population movement is accompanied by increased symptoms of physiological deconditioning, among which sleep disturbances stand out. In this scenario, napping is a counter measurement for sleep disturbances; however, its benefits or physiological changes at high altitudes have not been explored. Objective: To evaluate the physiological changes during a nap in conditions simulating high altitude. Methods: Randomized, single-blind, three period cross-over pilot study conducted with 15 healthy lowlander subjects (8 women) with a mean (SD) age of 29(6) years. Volunteers underwent an evaluation around a 90 min midday nap, being allocated to a randomized sequence of three conditions: FiO2 21% (NN), FiO2 14.7% (NH15) and 12.5% (NH13). Results: Compared to NN, RR during napping was shortened by 57 and 206 ms under NH15 and NH13 conditions, respectively (p <0.001). Sympathetic predominance was evident by HRV and increased epinephrine levels. Concomitantly, there were significant changes in endocrine parameters such as EPO (~6 UI/L) and cortisol (~100 nmol/L) (NH13 vs. NN, p < 0.001). Cognitive evaluation revealed changes in the color-word Stroop test. Although sleep efficiency was preserved, polysomnography showed lesser N3 and REM sleep, and periodic breathing, predominantly in men. Conclusions: although napping may have metabolic and cognitive benefits, its implementation as a counter measurement in conditions of altitudinal hypoxia should be carefully evaluated as it could increase the occurrence of sleep disturbances with consequences on autonomic, endocrine and respiratory systems. Abstract: Context: Whether due to geopolitical instability, as in Colombia or Venezuela, global warming, or simply tourism, the movement of lowlanders to high altitudes is increasing. This population movement is accompanied by increased symptoms of physiological deconditioning, among which sleep disturbances stand out. In this scenario, napping is a counter measurement for sleep disturbances; however, its benefits or physiological changes at high altitudes have not been explored. Objective: To evaluate the physiological changes during a nap in conditions simulating high altitude. Methods: Randomized, single-blind, three period cross-over pilot study conducted with 15 healthy lowlander subjects (8 women) with a mean (SD) age of 29(6) years. Volunteers underwent an evaluation around a 90 min midday nap, being allocated to a randomized sequence of three conditions: FiO2 21% (NN), FiO2 14.7% (NH15) and 12.5% (NH13). Results: Compared to NN, RR during napping was shortened by 57 and 206 ms under NH15 and NH13 conditions, respectively (p <0.001). Sympathetic predominance was evident by HRV and increased epinephrine levels. Concomitantly, there were significant changes in endocrine parameters such as EPO (~6 UI/L) and cortisol (~100 nmol/L) (NH13 vs. NN, p < 0.001). Cognitive evaluation revealed changes in the color-word Stroop test. Although sleep efficiency was preserved, polysomnography showed lesser N3 and REM sleep, and periodic breathing, predominantly in men. Conclusions: although napping may have metabolic and cognitive benefits, its implementation as a counter measurement in conditions of altitudinal hypoxia should be carefully evaluated as it could increase the occurrence of sleep disturbances with consequences on autonomic, endocrine and respiratory systems. Resumen: Contexto: Ya sea por inestabilidad geopolítica, como ocurre en Colombia o Venezuela, por el calentamiento global, o simplemente por turismo, cada vez el desplazamiento de nativos de bajas alturas hacia las grandes alturas es mayor. Este movimiento poblacional se acompaña de un incremento en síntomas de desacondicionamiento fisiológico dentro de los que destacan las perturbaciones del sueño. En este escenario la siesta aparece como una medida contrarreguladora para las alteraciones del sueño; sin embargo, sus beneficios o cambios fisiológicos en las grandes alturas no ha sido explorado. Objetivo: Evaluar los cambios fisiológicos durante una siesta en condiciones que simulan la altura. Metodología: Este fue un estudio piloto aleatorizado, ciego, cruzado llevado a cabo con 15 sujetos nativos de bajas alturas (8 mujeres) con una edad promedio de 29 años (D.E.=6 años). Los voluntarios fueron evaluados fisiológicamente alrededor a una siesta de aproximadamente 90 min, siendo dispuestos en una secuencia aleatoria de tres condiciones: FiO2 de 21% (NN), FiO2 de 14,7% (NH15) y de 12,5% (NH13), con un periodo de reposo entre condiciones de una semana. Resultados: Comparado con NN, los intervalor RR durante la siesta se acortaron significativamente (p < 0,001) en 57 ms (NH15) y 206 ms (NH13). El predominio simpático fue evidente por el análisis de la variabilidad de frecuencia cardiaca y los niveles aumentados de adrenalina. Concomitántemente, hubo cambios significativos en parámetros endocrinos tales como al eritropoyetina (~6 UI/L) y cortisol (~100 nmol/L) (NH13 VS. NN, p < 0,001). La evaluación cognitiva mostró cambios en la prueba de Stroop. Adicionalmente, aunque la eficiencia del sueño se preservó, los resultados polisomnográficos mostraron una disminución en el sueño profundo y MOR, y un incremento de respiración periódica, fundamentalmente en hombres. Conclusiones: aunque tomar la siesta pueda tener beneficios metabólicos y cognitivos, su implementación como contrarreguladora en condiciones de hipoxia altitudinal debe ser evaluada cuidadosamente ya que podría incrementar la aparición de perturbaciones del sueño con efectos en los sistemas autónomo, endocrino y respiratorio.

Abstract: Background: The association between prolonged non-nutritive sucking habits (NNSHs, ie, sucking pacifiers or fingers) and maxillofacial growth anomalies in the general population has been widely described. Because maturation of sucking abilities is not fully achieved in very preterm infants (< 32 weeks’ gestation), neonatal services worldwide rely on the use of pacifiers to promote the development of adequate sucking reflexes, possibly prolonging NNSHs during infancy. Objective: We aimed to describe the frequency and to identify factors associated with NNSHs at age 2 years in very preterm children. Methods: The study was based on data from EPIPAGE-2, a French national prospective cohort study of preterm births during 2011 that included 2593 children born between 24 and 31 weeks’ gestation. The primary outcome was NNSHs at 2 years. Multivariable log-linear regression models with generalized estimation equations were used to study the association between the characteristics studied and NNSHs. Multiple imputations were used to take into account missing data. Results: The frequency of NNSHs was 69% in the overall sample but higher among girls (adjusted risk ratio [RR] 1.12, 95% confidence interval [CI] 1.05, 1.17), children born from multiple pregnancies (eg, twins/triplets) (RR 1.07, 95% CI 1.00, 1.11), children who were fed by nasogastric tube (RR 1.07, 95% CI 1.01, 1.13), or those who benefitted from developmental care programmes (RR 1.10, 95% CI 1.02, 1.19). The NNSHs frequency was lower if mothers were not born in France (RR 0.70, 95% CI 0.64, 0.77), children had 2 or more older siblings (RR 0.88, 95% CI 0.82, 0.96), or children were breast-fed at discharge (RR 0.90, 95% CI 0.85, 0.95). Conclusions: NNSHs at 2 years seemed associated with cultural background, devel- opment care programmes, and breast feeding. Whether NNSHs at 2 years among very preterm children are associated with future maxillofacial growth anomalies deserves further attention. Resumen: Antecedentes: La asociación entre hábitos prolongados de succión no nutritiva (HSNN, es decir, chupar chupete o dedos) y anomalías del crecimiento maxilofacial en la población general ha sido ampliamente descrita. Debido a que la maduración de las habilidades de succión no se logra por completo en los bebés muy prematuros (< 32 semanas de gestación), los servicios neonatales de todo el mundo dependen del uso de chupetes para promover el desarrollo de reflejos de succión adecuados, lo que posiblemente prolongue los HSNN durante la infancia. Objetivo: Nuestro objetivo fue describir la frecuencia e identificar los factores asociados con los HSNN a los 2 años de edad en niños muy prematuros. Métodos: El estudio se basó en datos de EPIPAGE-2, un estudio de cohorte prospectivo nacional francés de nacimientos prematuros durante 2011 que incluyó a 2593 niños nacidos entre las semanas 24 y 31 de gestación. El criterio de interes primario fue HSNN a los 2 años. Se utilizaron modelos de regresión log-lineal multivariable con ecuaciones de estimación generalizadas para estudiar la asociación entre las características estudiadas y los HSNN. Se utilizaron imputaciones múltiples para tener en cuenta los datos faltantes. Resultados: La frecuencia de HSNN fue del 69 % en la muestra general, pero mayor entre las niñas, niños nacidos de embarazos múltiples (p. ej., gemelos/trillizos), niños alimentados por sonda nasogástrica, o aquellos que se beneficiaron de programas de atención del desarrollo. La frecuencia de HSNN fue menor si las madres no nacieron en Francia, los niños tenían 2 o más hermanos mayores, o los niños fueron amamantados al alta. Conclusiones: Los HSNN a los 2 años parecían estar asociados con los antecedentes culturales, los programas de atención del desarrollo y la lactancia materna. Si los HSNN a los 2 años entre los niños muy prematuros se asocian con futuras anomalías del crecimiento maxilofacial merece mayor atención.

Abstract: Introduction: Children born very preterm have an immature sucking reflex at birth and are exposed to neonatal care that can impede proper palate growth. Objectives: We aimed to describe the frequency of high-arched palate and posterior crossbite at the age of 5 in children born very preterm and to identify their respective risk factors. Methods: Our study was based on the data from EPIPAGE-2, a French national prospective cohort study, and included 2,594 children born between 24- and 31-week gestation. Outcomes were high-arched palate and posterior crossbite. Multivariable models estimated by generalized estimation equations with multiple imputation were used to study the association between the potential risk factors studied and each outcome. Results: Overall, 8 % of children born very preterm had a high-arched palate and 15 % posterior crossbite. The odds of high-arched palate were increased for children with low gestational age (24–29 vs. 30–31 weeks of gestation) [adjusted odds ratio (aOR) 1.76, 95% confidence interval (CI) 1.17, 2.66], thumb-sucking habits at the age of 2 (aOR 1.53, 95% CI 1.03, 2.28), and cerebral palsy (aOR 2.18, 95% CI 1.28, 3.69). The odds of posterior crossbite were increased for children with pacifier-sucking habits at the age of 2 (aOR 1.75, 95% CI 1.30, 2.36). Conclusions: Among very preterm children, low gestational age and cerebral palsy are the specific risk factors for a high-arched palate. High-arched palate and posterior crossbite share non-nutritive sucking habits as a common risk factor. The oro-facial growth of these children should be monitored. Resumen: Introducción: Los niños que nacen muy prematuros tienen un reflejo de succión inmaduro al nacer y están expuestos a cuidados neonatales que pueden impedir el correcto crecimiento del paladar. Objetivos: Nuestro objetivo fue describir la frecuencia de paladar ojival y mordida cruzada posterior a la edad de 5 años en niños nacidos muy prematuros e identificar sus respectivos factores de riesgo. Métodos: Nuestro estudio se basó en los datos de EPIPAGE-2, un estudio de cohorte prospectivo nacional francés, e incluyó a 2 594 niños nacidos entre las semanas 24 y 31 de gestación. Los resultados fueron paladar ojival y mordida cruzada posterior. Se utilizaron modelos multivariables estimados por ecuaciones de estimación generalizadas con imputación múltiple para estudiar la asociación entre los potenciales factores de riesgo estudiados y cada desenlace. Resultados: En general, el 8% de los niños nacidos muy prematuros tenían paladar ojival y el 15% mordida cruzada posterior. Las probabilidades de paladar ojival aumentaron para niños con edad gestacional baja (24–29 vs. 30–31 semanas de gestación) [odds ratio ajustado (ORa) 1,76, intervalo de confianza (IC) del 95 % 1,17, 2,66], hábito de succión del pulgar a los 2 años (ORa 1,53, IC 95% 1,03, 2,28), y parálisis cerebral (ORa 2,18, IC 95% 1,28, 3,69). Las probabilidades de mordida cruzada posterior aumentaron para los niños con hábitos de succión del chupete a la edad de 2 años (ORa 1,75, IC del 95%: 1,30, 2,36). Conclusiones: Entre los niños muy prematuros, la baja edad gestacional y la parálisis cerebral son los factores de riesgo específicos para paladar ojival. El paladar ojival y la mordida cruzada posterior comparten hábitos de succión no nutritiva como factor de riesgo común. El crecimiento orofacial de estos niños debe ser monitoreado.

Abstract: Health literacy aims to improve the ability to make decisions about our health and thus improve our quality of life. This is why the project JUNTOS (TOGETHER) aimed to do everything possible to promote health literacy, on the basis of a specific sociolinguistic problem. One of the objectives of this project was to carry out a quantitative readability analysis of written medical reports received by families with a child affected by a rare disease, as a way to account for the comprehension difficulty that these texts represent for these families. To carry out this analysis, we used different readability tools that currently exist for texts written in Spanish and English. The results we obtained led us to realize that there are some limitations that do not allow this type of quantitative analysis to be completely reliable when applied to specialized texts, specifically medical texts and more specifically medical reports; and at the same time they lead us to highlight the need to carry out parallel qualitative analyses when trying to make a readability analysis of specialized texts of this nature. Hence, the results of this research provide us with new ideas to continue working on this line of research. Resumen: La alfabetización en salud pretende mejorar la capacidad para tomar decisiones sobre nuestra salud y, por lo tanto, mejorar nuestra calidad de vida. Es por eso por lo que desde el proyecto JUNTOS se planteó hacer lo posible para favorecer esta alfabetización en salud, partiendo de un problema sociolingüístico en concreto. Uno de los objetivos de este proyecto fue hacer un análisis cuantitativo de legibilidad de informes médicos escritos recibidos por familias con un niño afectado por una enfermedad rara, como mecanismo para dar cuenta de la dificultad de comprensión que estos textos suponen para dichas familias. Para llevar a cabo este análisis aprovechamos diferentes herramientas de legibilidad que existen en la actualidad para textos escritos en español y en inglés. Los resultados que obtuvimos nos llevaron a darnos cuenta de que existen algunos limitantes que no permiten que este tipo de análisis cuantitativo sea completamente fiable cuando se aplica a textos especializados, en concreto, de medicina y más específicamente de informes médicos; y al mismo tiempo nos llevan a destacar la necesidad de realizar en paralelo análisis cualitativos cuando se pretende hacer un análisis de legibilidad de textos especializados de esta índole. De aquí que los resultados de esta investigación nos planteen nuevas ideas para seguir trabajando en esta línea de investigación.

Abstract: Sexual reproduction depends on the transmission of exactly one copy of each chromosome by the maternal and paternal gametes. This is accomplished during meiosis when diploid progenitors undergo two consecutive rounds of chromosome segregation following a single round of DNA replication. In most organisms, this relies on the establishment of bivalent chromosomes consisting of replicated parental homologues physically linked at sites of meiotic recombination. In female mammals, bivalents are formed during fetal development when the lifetime stock of primordial-stage oocytes is established. However, they are not resolved until shortly before ovulation. Extending this period beyond ~35 years results in a dramatic increase in embryo aneuploidy. Depletion of the lifetime stock of oocytes during ageing culminates in menopause. Our previous studies indicate that Rec8-containing cohesin complexes also become depleted from oocyte chromosomes during female ageing. Consistent with cohesin’s role in maintaining chromosome structure, depletion of Rec8 is associated with destabilisation of bivalents chromosomes. Nevertheless, the mechanisms and timing of cohesin depletion remain unknown. Here, I investigated the possibility that age-related cohesion depletion is a consequence of leaky inhibition of the protease separase, which cleaves Rec8 during anaphase. I found that oocyte-specific deletion of separase did not prevent depletion of oocyte cohesin during female ageing. I, therefore, conclude that age-related depletion occurs by a separaseindependent mechanism. I next investigated the timing, during oogenesis, at which cohesin loss occurs. I found that cohesin is predominantly lost at the primordial stage before oocytes are recruited for growth. In addition, using an oocyte-specific deletion of Pten, I determined that this occurs independently of the decline in the ovarian stock of primordial-stage oocytes. Together, these results indicate that age-related cohesin depletion occurs at the primordial stage by a separase-independent mechanism. Other possible of mechanisms of cohesin depletion include protein damage and/or agerelated deterioration of chromatin structure. From a clinical perspective, my work suggests that “rejuvenation’ of fertility by activating the residual pool of primordial oocytes is unlikely to be successful in older women.

Abstract: Evidence about the effectiveness of school closures as a measure to control the spread of COVID-19 is controversial. We posit that schools are not an important source of transmission; thus, we analyzed two surveillance methods: a web-based questionnaire and a telephone survey that monitored the impact of the pandemic due to COVID-19 cases in Bogotá, Colombia. We estimated the cumulative incidences for Acute Respiratory Infection (ARI) and COVID-19 for each population group. Then, we assessed the differences using the cumulative incidence ratio (CIR) and 95% confidence intervals (CI95%). The ARI incidence among students was 20.1 times higher when estimated from the telephone survey than from the online questionnaire (CIR: 20.1; CI95% 17.11–23.53). Likewise, the ARI incidence among choolteachers was 10 times higher in the telephone survey (CIR: 9.8; CI95% 8.3–11.5). The incidence of COVID-19 among schoolteachers was 4.3 times higher than among students in the online questionnarie (CIR: 4.3, CI95%: 3.8–5.0) and 2.1 times higher in the telephone survey (CIR = 2.1, CI95%: 1.8–2.6), and this behavior was also observed in the general population data. Both methods showed a capacity to detect COVID-19 transmission among students and schoolteachers, but the telephone survey estimates were probably closer to the real incidence rate. Resumen: La evidencia sobre la efectividad del cierre de las instituciones educativas como una medida para controlar la transmisión del COVID-19 es controversial. Nosotros postulamos que los colegios no son una fuente importante de transmisión, por lo tanto, se analizaron dos métodos de vigilancia: un cuestionario en línea y una encuesta telefónica que monitoreaba el impacto causado por los casos de la pandemia de COVID-19 en Bogotá, Colombia. Se estimó las incidencias acumuladas por infección respiratoria aguda (IRA) y COVID-19 para cada grupo poblacional. Posteriormente, se evaluaron las diferencias usando la tasa de incidencias acumuladas (TIA) con intervalos de confianza del 95%. La incidencia de IRA en los estudiantes fue 20.1 veces más alta cuando se estimó a partir de la encuesta telefónica frente al cuestionario en línea (TIA: 20.1; IC95% 17.11–23.53). Igualmente, la incidencia de ARI entre los docentes fue 10 veces más alta en la encuesta telefónica (TIA: 9.8; IC95% 8.3–11.5). La incidencia de COVID-19 en los docentes fue 4.3 veces más alta que la de los estudiantes de acuerdo con el cuestionario en línea (TIA: 4.3, IC95%: 3.8–5.0) y 2.1 veces más alta en la encuesta telefónica (CIR = 2.1, CI95%: 1.8–2.6), y este comportamiento también se observó en los datos de la población general. Ambos métodos de vigilancia mostraron ser capaces de detectar la transmisión del COVID-19 entre los estudiantes y los docentes, pero las estimaciones derivadas de la encuesta telefónica fueron probablemente más cercanas a las tasas de incidencia reales.

Abstract: Background: Although Latin American migrants (LAMs) are one of the fastest-growing migrant populations in England, they still face health barriers that make them unaware of their HIV status, leading to late HIV diagnosis, AIDS, and even death. Thus, this study aims to assess the differences in HIV outcomes among newly HIV-diagnosed LAMs compared to other England populations. Methods: Data on new HIV/AIDS diagnoses in the UK during the 2011-2020 period were obtained from the HIV and AIDS New Diagnoses and Deaths Database (HANDD) and the HIV and AIDS Reporting System (HARS). Potential associations between the region of birth and late HIV diagnosis, AIDS at HIV diagnosis, and mortality were analysed by logistic regression. Furthermore, a comparison between LAMs and the main populations living in the UK was examined. Lastly, a descriptive trend analysis was made. Results: From 2011 to 2020, 47,828 new HIV diagnoses were reported in the UK, with almost a third (29.2%) being late diagnoses. Over half of new diagnoses (52%) were made in migrants, LAMs representing 9.3% of those diagnoses. In general, newly diagnosed HIV LAMs are not more likely to be diagnosed late than UK residents (aRRR: 1.02; 95%CI: 0.90–1.15). However, some subgroups are more likely to be diagnosed late than their UK counterparts (e.g., 15-24 years old). Regarding AIDS and mortality, LAMs are less likely to be diagnosed with AIDS (aOR: 0.50; 95%CI: 0.35–0.71) or die by any cause (aOR: 0.29; 95%CI: 0.16–0.52) than UK residents. Finally, the number of new HIV diagnoses among LAMs increased in those ten years, but the number of late diagnoses remained nearly constant. Conclusions: Although the current HIV epidemiological situation of LAMs living in the UK is not troublesome, the expansion of the LAM population and their increasing number of new HIV diagnoses could become a public health challenge in the coming years. Therefore, to accomplish the 2030 zero HIV transmission goal, it is necessary to integrate the migrant community into future public policies and categorise them as the ‘sixth’ HIV key population in the UK.

Abstract: The evolution of multidrug resistance in Klebsiella species in response to selective pressure and the extent to which this may be reversible is not fully understood. The spread of carbapenemresistant Enterobacteriaceae (CRE) is considered a public health threat by the World Health Organization (WHO) and the Centers for Disease Control and Prevention (CDC). As such, more studies are needed to understand the evolution of antibiotic resistance mechanisms to determine if it is possible to reverse this trend. Highlighted In this study, a comprehensive characterisation of a clinical Klebsiella quasipneumoniae isolate called FK688 is performed. The FK688 strain is resistant to multiple antibiotics, including third-generation cephalosporins and carbapenems and caused a bloodstream infection in a hospitalised patient. A combinational approach of genomic, enzymatic, and machine learning analyses did not uncover any carbapenemase-encoding genes in FK688. Rather, this research showed that epistatic changes are necessary for FK688 to acquire a CRE phenotype. Evolution experiments demonstrated the fitness burden associated with antimicrobial resistance determinants and the reversion to a carbapenem-susceptible phenotype in an antibiotic-free environment. Fitness assays showed that a low concentration of ceftazidime selects for a ?- lactamase gene and can potentiate evolution to carbapenem resistance by a single-step mutation in the porin OmpK36. This study demonstrated the importance of epistatic events and how variation in drug exposure can shape the evolutionary pathway to antibiotic resistance in bacteria.