Succinct Indexable Dictionaries with Applications to Encoding kk-ary Trees, Prefix Sums and Multisets

We consider the {\it indexable dictionary} problem, which consists of storing a set $S \subseteq \{0,...,m-1\}$ for some integer $m$, while supporting the operations of \Rank(x), which returns the number of elements in $S$ that are less than $x$ if $x \in S$, and -1 otherwise; and \Select(i) which returns the $i$-th smallest element in $S$. We give a data structure that supports both operations in O(1) time on the RAM model and requires ${\cal B}(n,m) + o(n) + O(\lg \lg m)$ bits to store a set of size $n$, where {\cal B}(n,m) = \ceil{\lg {m \choose n}} is the minimum number of bits required to store any $n$-element subset from a universe of size $m$. Previous dictionaries taking this space only supported (yes/no) membership queries in O(1) time. In the cell probe model we can remove the $O(\lg \lg m)$ additive term in the space bound, answering a question raised by Fich and Miltersen, and Pagh. We present extensions and applications of our indexable dictionary data structure, including: An information-theoretically optimal representation of a $k$-ary cardinal tree that supports standard operations in constant time, A representation of a multiset of size $n$ from $\{0,...,m-1\}$ in ${\cal B}(n,m+n) + o(n)$ bits that supports (appropriate generalizations of) \Rank and \Select operations in constant time, and A representation of a sequence of $n$ non-negative integers summing up to $m$ in ${\cal B}(n,m+n) + o(n)$ bits that supports prefix sum queries in constant time.Comment: Final version of SODA 2002 paper; supersedes Leicester Tech report 2002/1

Outcomes of Comprehensive Care for Children Empirically Treated for Multidrug-Resistant Tuberculosis in a Setting of High HIV Prevalence

Background: Few studies have examined outcomes for children treated for multidrug-resistant tuberculosis (MDR-TB), including those receiving concomitant treatment for MDR-TB and HIV co-infection. In Lesotho, where the adult HIV seroprevalence is estimated to be 24%, we sought to measure outcomes and adverse events in a cohort of children treated for MDR-TB using a community-based treatment delivery model. Methods: We reviewed retrospectively the clinical charts of children $\leq$15 years of age treated for culture-confirmed or suspected MDR-TB between July 2007 and January 2011. Results: Nineteen children, ages two to 15, received treatment. At baseline, 74% of patients were co-infected with HIV, 63% were malnourished, 84% had severe radiographic findings, and 21% had extrapulmonary disease. Five (26%) children had culture-confirmed MDR-TB, ten (53%) did not have culture results available, and four (21%) subsequently had results indicating drug-susceptible TB. All children with HIV co-infection who were not already on antiretroviral therapy (ART) were initiated on ART a median of two weeks after the start of the MDR-TB regimen. Among the 17 patients with final outcomes, 15 (88%) patients were cured or completed treatment, two (12%) patients died, and none defaulted or were lost to follow-up. The majority of patients (95%) experienced adverse events; only two required permanent discontinuation of the offending agent, and only one required suspension of MDR-TB treatment for more than one week. Conclusions: Pediatric MDR-TB and MDR-TB/HIV co-infection can be successfully treated using a combination of social support, close monitoring by community health workers and clinicians, and inpatient care when needed. In this cohort, adverse events were well tolerated and treatment outcomes were comparable to those reported in children with drug-susceptible TB and no HIV infection

Arrhythmias and conduction disturbances in patients with systemic sclerosis—A systematic literature review

Systemic sclerosis (SSc) is an autoimmune disease characterized by skin and internal organ fibrosis and microvascular impairment, which can affect major organs, including the heart. Arrhythmias are responsible for approximately 6% of deaths in patients with SSc, and mainly occur due to myocardial fibrosis, which causes electrical inhomogeneity. The aim of this study was to determine the frequency of arrhythmias and conduction disturbances in SSc cohorts, and to identify the characteristics and risk factors associated with the occurrence of dysrhythmias in patients with SSc. A systematic literature review using PubMed, Embase, Web of Science and Scopus databases was performed. Full-text articles in English with arrhythmias as the main topic published until 21 April 2022 were included. Most prevalent arrhythmias were premature supraventricular and ventricular contractions, while the most frequent conduction disturbance was represented by right bundle branch block (RBBB). Elevated concentrations of N-terminal prohormones of brain natriuretic peptides (NT-pro BNP) were associated with numerous types of atrial and ventricular arrhythmias, and with the occurrence of RBBB. A lower value of the turbulence slope (TS) emerged as an independent predictor for ventricular arrhythmias. In conclusion, dysrhythmias are frequent in SSc cohorts. Paraclinical and laboratory parameters are useful instruments that could lead to early diagnosis in the course of the disease

Risk of diabetes mellitus among users of immune checkpoint inhibitors: A population‐based cohort study

Background Immune checkpoint inhibitors (ICIs) are increasingly established cancer therapeutics, but they are associated with new-onset diabetes mellitus (DM). Such risks have not been adequately quantified, and between-class and -sex differences remain unexplored. Methods This was a prospective cohort study of cancer patients receiving any ICI in Hong Kong between 2013 and 2021. Patients with known DM were excluded. Due to few patients using other ICIs, only programmed cell death 1 inhibitors (PD-1i) and programmed death ligand 1 inhibitors (PD-L1i) were compared, alongside between-sex comparison. When comparing PD-1i against PD-L1i, patients with the use of other ICIs or both PD-1i and PD-L1 were further excluded. Inverse probability treatment weighting (IPTW) was used to minimize between-group covariate imbalances. Results Altogether, 3375 patients were analyzed (65.2% males, median age 62.2 [interquartile range 53.8–69.5] years old). Over a median follow-up of 1.0 [0.4–2.4] years, new-onset DM occurred in 457 patients (13.5%), with a 3-year risk of 14.5% [95% confidence interval 13.3%, 15.8%]. IPTW achieve acceptable covariate balance between sexes, and between PD-1i (N = 622) and PD-L1i (N = 2426) users. Males had significantly higher risk of new-onset DM (hazard ratio 1.35 [1.09, 1.67], p = 0.006), while PD-1i and PD-L1i users did not have significantly different risks (hazard ratio vs PD-L1i 0.81 [0.59, 1.11], p = 0.182). These were consistent in those with at least 1 year of follow-up, and on competing risk regression. Conclusion Users of ICI may have a substantial risk of new-onset DM, which may be higher in males but did not differ between PD-1i and PD-L1i

Associations between social determinants of health and cardiovascular and cancer mortality in cancer survivors: a prospective cohort study

Aims The cause-specific mortality implications of social determinants of health (SDOH) in cancer survivors were unclear. This study aimed to explore associations between SDOH and cardiovascular and cancer mortality in cancer survivors. Methods and results Data from 2013 to 2017 National Health Interview Survey were used for this prospective cohort study. Social determinants of health were quantified using a 38 point, 6 domain score, with higher points indicating worse deprivation. Associations between SDOH and outcomes (primary: cardiovascular mortality; secondary: cancer and all-cause mortality) were assessed using cause-specific multivariable Cox regression, with cancer survivors and individuals without cancer modelled separately. Post hoc analyses were performed among cancer survivors to explore associations between each domain of SDOH and the risks of outcomes. Altogether, 37 882 individuals were analysed (4179 cancer survivors and 33 703 individuals without cancer). Among cancer survivors, worse SDOH was associated with higher cardiovascular [adjusted hazard ratio (aHR) 1.31 (1.02–1.68)], cancer [aHR 1.20 (1.01–1.42)], and all-cause mortality [aHR 1.16 (1.02–1.31)] when adjusted for demographics, comorbidities, and risk factors. Among individuals without cancer, SDOH was associated with cardiovascular mortality and all-cause when only adjusted for demographics, but not when further adjusted for comorbidities and risk factors; no associations between SDOH and cancer mortality were found. Among cancer survivors, psychological distress, economic stability, neighbourhood, physical environment and social cohesion, and food insecurity were varyingly associated with the outcomes. Conclusion Social determinants of health were independently associated with all-cause, cardiovascular, and cancer mortality among cancer survivors but not among individuals without cancer. Different domains of SDOH may have different prognostic importance

Stronger diversity effects with increased environmental stress : a study of multitrophic interactions between oak, powdery mildew and ladybirds

Recent research has suggested that increasing neighbourhood tree species diversity may mitigate the impact of pests or pathogens by supporting the activities of their natural enemies and/or reducing the density of available hosts. In this study, we attempted to assess these mechanisms in a multitrophic study system of young oak (Quercus), oak powdery mildew (PM, caused by Erysiphe spp.) and a mycophagous ladybird (Psyllobora vigintiduo-punctata). We assessed ladybird mycophagy on oak PM in function of different neighbourhood tree species compositions. We also evaluated whether these species interactions were modulated by environmental conditions as suggested by the Stress Gradient Hypothesis. We adopted a complementary approach of a field experiment where we monitored oak saplings subjected to a reduced rainfall gradient in a young planted forest consisting of different tree species mixtures, as well as a lab experiment where we independently evaluated the effect of different watering treatments on PM infections and ladybird mycophagy. In the field experiment, we found effects of neighbourhood tree species richness on ladybird mycophagy becoming more positive as the target trees received less water. This effect was only found as weather conditions grew drier. In the lab experiment, we found a preference of ladybirds to graze on infected leaves from trees that received less water. We discuss potential mechanisms that might explain this preference, such as emissions of volatile leaf chemicals. Our results are in line with the expectations of the Natural Enemies Hypothesis and support the hypothesis that biodiversity effects become stronger with increased environmental stress

Performance of the 2007 WHO Algorithm to diagnose Smear-negative Pulmonary Tuberculosis in a HIV prevalent setting

The 2007 WHO algorithm for diagnosis of smear-negative pulmonary tuberculosis (PTB) including Mycobacterium tuberculosis (MTB) culture was evaluated in a HIV prevalent area of Kenya

Virtual medical research mentoring

Background Medical research is important for professional advancement, and mentoring is a key means by which students and early-career doctors can engage in research. Contrasting international research collaborations, research mentoring programmes are often geographically limited. As the COVID-19 pandemic has led to increased use of online technology for classes and conferences, a virtual, international approach to medical research mentoring may be valuable. Approach We hereby describe our experience at the Cardiovascular Analytics Group, a virtual international medical research mentoring group established in 2015. We make use of virtual platforms in multi-level mentoring with peer mentoring and emphasise active participation, early leadership, an open culture, accessible research support and a distributed research workflow. Evaluation With 63 active members from 14 different countries, the Group has been successful in training medical students and early-career medical graduates in academic medicine. Our members have led over 100 peer-reviewed publications of original research and reviews since 2015, winning 13 research prizes during this time. Implications Our accessible-distributed model of virtual international medical research collaboration and multi-level mentoring is viable and efficient and caters to the needs of contemporary healthcare. Others should consider building similar models to improve medical research mentoring globally

Development of a non-human primate BCG infection model for the evaluation of candidate tuberculosis vaccines.

The lack of validated immunological correlates of protection makes tuberculosis vaccine development difficult and expensive. Using intradermal bacille Calmette-Guréin (BCG) as a surrogate for aerosol Mycobacterium tuberculosis (M.tb) in a controlled human infection model could facilitate vaccine development, but such a model requires preclinical validation. Non-human primates (NHPs) may provide the best model in which to do this. Cynomolgus and rhesus macaques were infected with BCG by intradermal injection. BCG was quantified from a skin biopsy of the infection site and from draining axillary lymph nodes, by culture on solid agar and quantitative polymerase chain reaction. BCG was detected up to 28 days post-infection, with higher amounts of BCG detected in lymph nodes after high dose compared to standard dose infection. Quantifying BCG from lymph nodes of cynomolgus macaques 14 days post-high dose infection showed a significant reduction in the amount of BCG detected in the BCG-vaccinated compared to BCG-naïve animals. Demonstrating a detectable vaccine effect in the lymph nodes of cynomolgus macaques, which is similar in magnitude to that seen in an aerosol M.tb infection model, provides support for proof-of-concept of an intradermal BCG infection model and evidence to support the further evaluation of a human BCG infection model