A dynamical measure of the black hole mass in a quasar 11 billion years ago.

Tight relationships exist in the local Universe between the central stellar properties of galaxies and the mass of their supermassive black hole (SMBH)1-3. These suggest that galaxies and black holes co-evolve, with the main regulation mechanism being energetic feedback from accretion onto the black hole during its quasar phase4-6. A crucial question is how the relationship between black holes and galaxies evolves with time; a key epoch to examine this relationship is at the peaks of star formation and black hole growth 8-12 billion years ago (redshifts 1-3)7. Here we report a dynamical measurement of the mass of the black hole in a luminous quasar at a redshift of 2, with a look back in time of 11 billion years, by spatially resolving the broad-line region (BLR). We detect a 40-µas (0.31-pc) spatial offset between the red and blue photocentres of the Hα line that traces the velocity gradient of a rotating BLR. The flux and differential phase spectra are well reproduced by a thick, moderately inclined disk of gas clouds within the sphere of influence of a central black hole with a mass of 3.2 × 108 solar masses. Molecular gas data reveal a dynamical mass for the host galaxy of 6 × 1011 solar masses, which indicates an undermassive black hole accreting at a super-Eddington rate. This suggests a host galaxy that grew faster than the SMBH, indicating a delay between galaxy and black hole formation for some systems.

[Quality of "crisis communication" media during the COVID-19 pandemic in the Great Maghreb countries]. / Qualité des supports de communication de crise lors de la pandémie de la COVID-19 au Grand Maghreb.

OBJECTIVE: To objectively assess the quality of "crisis communication" media, during the COVID-19 pandemic, in the three Greater Maghreb countries (Tunisia, Algeria, Morocco). METHODS: A compliance audit for press releases and epidemiological bulletins was analyzed against a quality benchmark, which had been specifically designed by the authors. This framework, made up of five dimensions and 50 items, graded (0/1), was applied by two researchers in preventive medicine. Multiplying the scores by a coefficient of two resulted in a partial score of 20 points for each dimension and a total score of 100 points for the checklist taken as a whole. The quality of the communication media was considered to be good when exceeding the thresholds of 15/20 for the different dimensions and 75/100 for the entire grid. RESULTS: A total of 141 information media were included in this audit (Tunisia: 60; Algeria: 60; Morocco: 21). The overall median quality score for these media was only 56/100 (IIQ: [46-58]), without major variability between countries. The most appreciated dimension was "maintaining the confidence of the population", with an overall median score of 14/20 (12/20 for epidemiological bulletins and 16/20 for press releases). The most poorly rated dimension was "strengthening community participation", with a median score of only 4/20 (6/20 for epidemiological bulletins and 4/20 for press releases). CONCLUSION: The quality of the Maghreb crisis communication media during COVID-19 was insufficient in most of its dimensions and items, particularly from a psychosocial standpoint. Reinforcement of the capacities of communication officers to develop information material and supports during health crises is indispensable and should be considered as an urgent matter.

Bartonella bovis and Bartonella chomelii infection in dairy cattle and their ectoparasites in Algeria.

Bartonella are blood-borne and vector-transmitted bacteria, some of which are zoonotic. B. bovis and B. chomelii have been reported in cattle. However, no information has yet been provided on Bartonella infection in cattle in Algeria. Therefore, 313 cattle from 45 dairy farms were surveyed in Kabylia, Algeria, in order to identify Bartonella species infecting cattle using serological and molecular tests. In addition, 277 ticks and 33 Hippoboscidae flies were collected. Bartonella bovis and B. chomelii were identified as the two species infecting cattle. Bartonella DNA was also amplified from 6.8 % (n = 19) of ticks and 78.8 % (n = 26) of flies. Prevalence of B. bovis DNA in dairy cattle was associated both with age and altitude. This study is the first one to report of bovine bartonellosis in Algeria, both in dairy cattle and in potential Bartonella vectors, with the detection of B. bovis DNA in tick samples and B. chomelii in fly samples.

Acquired generalized lipodystrophy under immune checkpoint inhibition.

Immune checkpoint inhibitors are now the standard of care in the treatment of several types of cancer. Cutaneous immune-related adverse events (irAEs) are usually of low grade and reversible, while endocrine irAEs are generally irreversible and managed with hormone replacement therapy. We report a 47-year-old patient, treated with the anti-programmed cell death (PD)1 antibody pembrolizumab for a metastatic melanoma, who developed severe lipodystrophy after 10 months of treatment, characterized by the loss of subcutaneous fat tissue, central obesity and insulin resistance with a decreased leptin level. Histological analysis of a cutaneous biopsy revealed subcutaneous fat cell destruction associated with oedema, the presence of lipophages, and a CD3+ lymphocytic infiltrate involving the panniculus. This led to the diagnosis of anti-PD-1-induced acquired generalized lipodystrophy, after ruling out differential diagnoses (i.e. genetic and systemic autoimmune diseases). No corticosteroids were introduced considering the high risk of inducing severe metabolic complications, and pembrolizumab was discontinued as complete response of the melanoma was achieved. However, after 12 months of follow-up, lipodystrophy and its severe metabolic complications are still ongoing. What's already known about this topic? Anti-programmed cell death (PD)1 agents are now a standard of care in the treatment of several cancers, including melanoma. Endocrine and cutaneous immune-related adverse events (irAEs) are among the most frequent irAEs (14-30% and 30-40%, respectively) in patients treated with immune checkpoint inhibitors. What does this study add? Acquired generalized lipodystrophy can occur during anti-PD1 therapy and is associated with severe metabolic complications. With the increase in anti-PD1 prescription in several cancer types, clinicians must be aware of the whole range of irAEs that may occur.

Newly diagnosed cases of HIV in those aged 50 years and older and those less than 50: 2008-2017.

BACKGROUND: Canada's population is aging, with nearly forty percent of Canadians aged 50 years or more. As the population ages, unique challenges related to health are becoming evident, including increasing rates of sexually transmitted and bloodborne infections. Understanding the epidemiology of HIV in older adults is important to guide prevention and control programs. OBJECTIVE: To assess trends in newly diagnosed cases of HIV in Canada among those aged 50 years and older (≥50 years) and those aged less than 50 (<50 years), and to compare their basic demographic characteristics and exposure categories for the period of 2008 to 2017. METHODS: National surveillance of HIV is conducted by the Public Health Agency of Canada through voluntary submission of data by provincial/territorial public health authorities. Descriptive analyses were conducted on reported cases of HIV between January 1, 2008, to December 31, 2017 to compare the demographic profiles and exposure category for the two age groups. RESULTS: Between 2008 and 2017, the proportion of newly diagnosed HIV cases among those ≥50 years increased from 15.1% to 22.8%. The HIV diagnosis rates for both older males and older females increased over time, with a relatively higher increase for females. A higher proportion of newly diagnosed HIV cases were male in the older group (81.2%) compared to the younger group (74.6%). Among both older and younger males, the most common exposure category for HIV was being gay, bisexual and other men who have sex with men (gbMSM), followed by heterosexual contact and injection drug use; however, the relative proportions varied by age with the gbMSM category being higher in the <50 group. CONCLUSION: In Canada, over 20% of all newly diagnosed cases of HIV are now in people 50 years of age and older. HIV testing and prevention initiatives, historically aimed at younger populations, may not have the same impact for older populations. These data can be used to inform future public health actions designed to address HIV in older populations.

HIV in Canada-Surveillance Report, 2018.

BACKGROUND: Human immunodeficiency virus (HIV) is a global public health issue, with an estimated 36.9 million people living with HIV in 2017. HIV has been reportable in Canada since 1985 and the Public Health Agency of Canada (PHAC) continues to monitor trends in new HIV diagnoses. OBJECTIVE: The objective of this surveillance report is to provide an overview of the epidemiology of all reported diagnoses of HIV in Canada since 1985 with a focus on 2018 overall, and by geographic location, age group, sex, and exposure category. METHODS: PHAC monitors HIV through the national HIV/AIDS Surveillance System, a passive, case-based system that collates nonnominal data that is voluntarily submitted by all Canadian provinces and territories. Descriptive epidemiological analyses were conducted on national data and those relating to specific populations provided by Immigration, Refugees and Citizenship Canada and the Canadian Perinatal HIV Surveillance Program. RESULTS: In 2018, a total of 2,561 HIV diagnoses were reported in Canada, an increase of 8.2% compared with 2017. The national diagnosis rate increased to 6.9 per 100,000 population in 2018 from 6.5 per 100,000 population in 2017. Saskatchewan reported the highest provincial diagnosis rate at 14.9 per 100,000 population. The 30-39 year age group continued to have the highest HIV diagnosis rate at 15.4 per 100,000 population. Overall, the diagnosis rate for males continued to be higher than that of females (9.8 versus 4.0 per 100,000 population, respectively); however, females experienced a larger increase in reported cases and diagnosis rate. The gay, bisexual and other men who have sex with men (gbMSM) exposure category continued to represent the highest proportion of all reported adult cases (41.4%), though the proportion has decreased over time. Five perinatal HIV transmissions were documented, three were related to the mother not receiving perinatal antiretroviral therapy prophylaxis. CONCLUSION: The number and rate of reported HIV cases in Canada increased in 2018, gbMSM continued to account for the largest exposure category and the number and rate of reported HIV cases among women increased. PHAC will continue to work with its national partners to refine the collection, analysis and publication of national data to better understand the burden of HIV in Canada.

Improving national surveillance of new HIV diagnoses.

The purpose of national HIV surveillance is to track and summarize trends in newly diagnosed cases as an indicator of HIV transmission within Canada, and supports the development and evaluation of programs and policies for prevention, testing and delivery of care. Accurately capturing and interpreting trends in HIV diagnoses within national surveillance becomes complicated when there is movement of people within a country or when individuals are diagnosed with HIV prior to migrating to a new country. This has been identified as an issue in other countries, including Australia, New Zealand and Switzerland. The Public Health Agency of Canada (PHAC) recently assessed this in Canada after noting a rise in new HIV cases in Canada between 2014 to 2017. An environmental scan was conducted to better understand how new and previously diagnosed cases of HIV were recorded by and reported to PHAC from provincial and territorial (PT) public health authorities. It was discovered there was variation with respect to the reporting of cases who had received a new diagnosis of HIV within the province or territory, but who had previously received an HIV diagnosis from another PT or another country. Five PTs included cases previously diagnosed in another Canadian PT within the HIV surveillance data reported to PHAC and nine PTs included people who were diagnosed with HIV outside of Canada. The provincial and territorial public health authorities then reviewed HIV surveillance data from 2007 to 2017 to identify cases using a common definition of "previous HIV-positive test result". This included any case who gave a history, or had laboratory evidence, of an HIV-positive result from another PT or another country before presenting for care in the province or territory where they now resided. When these cases were subtracted from the total, a revised number of new HIV diagnoses was calculated for Canada. Re-analysis of surveillance data using this common definition for 2007 to 2017 explained more than half of the increase in HIV cases that had been documented in Canada over the last four years. In the future, national surveillance data will be calculated adopting this new common definition of a previous positive test result, in order to more accurately describe the trends in HIV transmission occurring in Canada.

Next-generation sequence data demonstrate several pathogenic bee viruses in Middle East and African honey bee subspecies (Apis mellifera syriaca, Apis mellifera intermissa) as well as their cohabiting pathogenic mites (Varroa destructor).

RNA viruses are associated with honey bee (Apis mellifera) colony losses in many parts of the world. Their consequences may be exacerbated when the ectoparasite mite Varroa destructor is present in hives. While evidence of pathogenic, viral-induced disease is abundant in western honey bees (Apis mellifera mellifera) from many parts of the world, less information exists regarding the pathogen load of Apis mellifera syriaca and Apis mellifera intermissa, honey bees from the Middle East and North Africa (MENA) that play substantial roles in regional beekeeping. Here, we used next-generation sequencing to evaluate the viral populations of these subspecies and their associated mites. We found that both A. m. syriaca and A. m. intermissa, as well as the Varroa mites infecting their colonies, bear a suite of RNA viruses including major pathogenic viruses like Deformed wing virus, Acute bee paralysis virus, Black queen cell virus and Sacbrood virus, and less common viruses (e.g., bee Macula-like virus and Apis mellifera filamentous virus). The two native honey bee MENA subspecies have acquired different but overlapping suites of pathogens, which also differ, but overlap, with the suites detected in the mites. The presence of plant viruses suggests that they were acquired from foraging for pollen and nectar. Phylogenetic analysis of the above common pathogenic RNA viruses showed unexpected genetic relationships with other known strains, indicative of import to MENA from outside of the region. Our findings indicate that it is important to carefully consider the impact of the movement of queens and mobile colonies, and the effects such movement have, on the transmission of disease.

Bovine anaplasmosis and tick-borne pathogens in cattle of the Galapagos Islands.

A cross-sectional study was conducted to determine the species of Anaplasma spp. and estimate its prevalence in cattle of the three main cattle-producing Galapagos Islands (Santa Cruz, San Cristóbal and Isabela) using indirect PCR assays, genetic sequencing and ELISA. Ticks were also collected from cattle and scanned for 47 tick-borne pathogens in a 48 × 48 real-time PCR chip. A mixed effects logistic regression was performed to identify potential risk factors explaining Anaplasma infection in cattle. A. phagocytophilum was not detected in any of the tested animals. Genetic sequencing allowed detection of A. platys-like strains in 11 (36.7%) of the 30 Anaplasma spp.-positive samples analysed. A. marginale was widespread in the three islands with a global between-herd prevalence of 100% [89; 100]95% CI and a median within-herd prevalence of 93%. A significant association was found between A. marginale infection and age with higher odds of being positive for adults (OR = 3.3 [1.2; 9.9]95% Bootstrap CI ). All collected ticks were identified as Rhipicephalus microplus. A. marginale, Babesia bigemina, Borrelia theileri and Francisella-like endosymbiont were detected in tick pools. These results show that the Galapagos Islands are endemic for A. marginale.

HIV in Canada-Surveillance Report, 2017.

BACKGROUND: Human immunodeficiency virus (HIV) is a global public health issue with an estimated 1.8 million people newly infected in 2017. OBJECTIVE: To provide a descriptive overview of reported cases of HIV in Canada by geographic location, sex, age group, exposure category and race/ethnicity, from 1985-2017, with a focus on the most recent data. METHODS: The Public Health Agency of Canada (PHAC) monitors HIV through the national HIV/AIDS Surveillance System, which is a passive, case-based system that collates non-nominal data voluntarily submitted and validated by all Canadian provinces and territories. Additional data sources presented here include data on immigration-related medical screening for HIV by Immigration, Refugees and Citizenship Canada and data on infants perinatally-exposed to HIV submitted by the Canadian Perinatal HIV Surveillance Program. Data were collated, tables and figures were prepared and descriptive statistics were applied by PHAC and validated by each province and territory. RESULTS: A total of 2,402 new HIV diagnoses were reported in 2017 in Canada; an increase of 3% compared with 2016 and an increase of 17.1% since 2014. The national diagnosis rate increased slightly, from 6.4 per 100,000 population in 2016 to 6.5 per 100,000 population in 2017. In 2017, while Ontario continued to account for the highest number (n=935) and proportion (38.9%) of reported HIV cases, Saskatchewan reported the highest provincial diagnosis rate (15.5 per 100,000 population). In 2017, the diagnostic rate for males at 9.9 per 100,000 population was higher than for females at 3.2 per 100,000 population. As in 2016, the 30-39 year age group had the highest HIV diagnosis rate at 14.8 per 100,000 population. The "gay, bisexual and other men who have sex with men" exposure category continued to represent almost half (46.4%) of all reported HIV cases in adults. In 2017, the absolute number of HIV-positive migrants entering Canada increased to a total number of 835 migrants. One mother-to-child HIV transmission was confirmed in a mother who did not receive any perinatal antiretroviral therapy and two transmissions were confirmed in mothers who did receive perinatal antiretroviral therapy. CONCLUSION: Similar to the annual changes that have been reported since 2014, the number and rate of reported HIV cases in Canada in 2017 increased slightly compared with 2016. Additional data and analysis are needed to determine the extent to which these findings reflect an increase in HIV transmission, an increase in HIV testing, changes in reporting practices and an increase in the number of HIV-positive people migrating to Canada.

Perspectives: using polymer modeling to understand the formation and function of nuclear compartments.

Compartmentalization is a ubiquitous feature of cellular function. In the nucleus, early observations revealed a non-random spatial organization of the genome with a large-scale segregation between transcriptionally active-euchromatin-and silenced-heterochromatin-parts of the genome. Recent advances in genome-wide mapping and imaging techniques have strikingly improved the resolution at which nuclear genome folding can be analyzed and have revealed a multiscale spatial compartmentalization with increasing evidences that such compartment may indeed result from and participate to genome function. Understanding the underlying mechanisms of genome folding and in particular the link to gene regulation requires a cross-disciplinary approach that combines the new high-resolution techniques with computational modeling of chromatin and chromosomes. In this perspective article, we first present how the copolymer theoretical framework can account for the genome compartmentalization. We then suggest, in a second part, that compartments may act as a "nanoreactor," increasing the robustness of either activation or repression by enhancing the local concentration of regulators. We conclude with the need to develop a new framework, namely the "living chromatin" model that will allow to explicitly investigate the coupling between spatial compartmentalization and gene regulation.

High Prevalence of Anaplasma spp. in Small Ruminants in Morocco.

The prevalence of infection by Anaplasma spp. (including Anaplasma phagocytophilum) was determined using blood smear microscopy and PCR through screening of small ruminant blood samples collected from seven regions of Morocco. Co-infections of Anaplasma spp., Babesia spp, Theileria spp. and Mycoplasma spp. were investigated and risk factors for Anaplasma spp. infection assessed. A total of 422 small ruminant blood samples were randomly collected from 70 flocks. Individual animal (breed, age, tick burden and previous treatment) and flock data (GPS coordinate of farm, size of flock and livestock production system) were collected. Upon examination of blood smears, 375 blood samples (88.9%) were found to contain Anaplasma-like erythrocytic inclusion bodies. Upon screening with a large spectrum PCR targeting the Anaplasma 16S rRNA region, 303 (71%) samples were found to be positive. All 303 samples screened with the A. phagocytophilum-specific PCR, which targets the msp2 region, were found to be negative. Differences in prevalence were found to be statistically significant with regard to region, altitude, flock size, livestock production system, grazing system, presence of clinical cases and application of tick and tick-borne diseases prophylactic measures. Kappa analysis revealed a poor concordance between microscopy and PCR (k = 0.14). Agreement with PCR is improved by considering microscopy and packed cell volume (PCV) in parallel. The prevalence of double infections was found to be 1.7, 2.5 and 24% for Anaplasma-Babesia, Anaplasma-Mycoplasma and Anaplasma-Theileria, respectively. Co-infection with three or more haemoparasites was found in 1.6% of animals examined. In conclusion, we demonstrate the high burden of anaplasmosis in small ruminants in Morocco and the high prevalence of co-infections of tick-borne diseases. There is an urgent need to improve the control of this neglected group of diseases.

Short Report: Identification of a Potential Marker of Anaplasma Phagocytophilum Associated with Cattle Abortion.

Anaplasma phagocytophilum is a tick-borne pathogen that causes tick-borne fever in domestic ruminants. Tick-borne fever is characterized by diverse symptoms and occasionally causes abortions in domestic ruminants, resulting in significant economic impact. However, in France, the potential frequency of A. phagocytophilum-related abortions is unknown, and thus, it remains difficult to estimate the full extent of its economic impact. This gap in our knowledge is likely explained, at least in part, by the absence of suitable and specific tools capable of detecting A. phagocytophilum associated with abortion. Our objective was to identify a genetic marker able to differentiate A. phagocytophilum strains isolated from domestic ruminants that had aborted compared to those that had not. Thus, we typed a total of 123 A. phagocytophilum obtained from cattle, of which 25 originated from cows that had aborted, via multiple-locus variable-number tandem repeat (VNTR) analysis. These included 56 new A. phagocytophilum samples and 67 previously published A. phagocytophilum samples. A multivariate logistic model demonstrated that the triple-repeat allele of the APV-A VNTR was statistically more frequent in A. phagocytophilum from cattle that had aborted, compared to A. phagocytophilum from cattle that had not aborted (P = 0.03), while controlling for any regional effects (P < 0.0001). For four other VNTR, there were no statistical associations between specific alleles and abortion. The APV-A triple-repeat VNTR allele could thus act as a marker of A. phagocytophilum involved in abortions. If this hypothesis is confirmed in additional samples from other regions, this marker could then be utilized in the development of A. phagocytophilum abortive strain surveillance measures.

Factors Affecting the Geo-effectiveness of Shocks and Sheaths at 1 AU.

We identify all fast-mode forward shocks, whose sheath regions resulted in a moderate (56 cases) or intense (38 cases) geomagnetic storm during 18.5 years from January 1997 to June 2015. We study their main properties, interplanetary causes and geo-effects. We find that half (49/94) such shocks are associated with interacting coronal mass ejections (CMEs), as they are either shocks propagating into a preceding CME (35 cases) or a shock propagating into the sheath region of a preceding shock (14 cases). About half (22/45) of the shocks driven by isolated transients and which have geo-effective sheaths compress pre-existing southward Bz . Most of the remaining sheaths appear to have planar structures with southward magnetic fields, including some with planar structures consistent with field line draping ahead of the magnetic ejecta. A typical (median) geo-effective shock-sheath structure drives a geomagnetic storm with peak Dst of -88 nT, pushes the subsolar magnetopause location to 6.3 RE, i.e. below geosynchronous orbit and is associated with substorms with a peak AL-index of -1350 nT. There are some important differences between sheaths associated with CME-CME interaction (stronger storms) and those associated with isolated CMEs (stronger compression of the magnetosphere). We detail six case studies of different types of geo-effective shock-sheaths, as well as two events for which there was no geomagnetic storm but other magnetospheric effects. Finally, we discuss our results in terms of space weather forecasting, and potential effects on Earth's radiation belts.

Habitat restoration affects immature stages of a wetland butterfly through indirect effects on predation.

Habitat loss worldwide has led to the widespread use of restoration practices for the recovery of imperiled species. However, recovery success may be hampered by focusing on plant communities, rather than the complex suite of direct and indirect interactions among trophic levels that occur in natural systems. Through a factorial field experiment, we tested the effects of wetland restoration on egg and juvenile survival of a locally rare butterfly, Satyrodes appalachia, via tree removal and damming. Tree removal more than tripled S. appalachia host plant abundance, but neither restoration action directly affected S. appalachia egg and juvenile survival. Instead, we found strong indirect effects of habitat manipulation on S. appalachia egg and juvenile survival that were mediated through predation. The interaction of tree removal and damming significantly decreased predation of S. appalachia eggs relative to each treatment alone. Damming alone had a significant positive indirect effect on the survival of S. appalachia juveniles, likely because increases in standing water reduced predator access. Our results emphasize the need for experiments that evaluate the demographic responses of imperiled species to habitat restoration prior to management action and quantify potential indirect effects mediated through higher trophic levels.

Traumatic flap dislocation 10 years after LASIK. Case report and literature review.

We report a case of traumatic partial flap dislocation 10 years after uneventful laser in situ keratomileusis (LASIK). The patient was treated bilaterally for hyperopia and astigmatism with LASIK. A superior-hinged corneal flap was created using the Moria M2 microkeratome (Moria SA, Antony, France) and the surgery was uneventful. Ten years later, partial flap dislocation was diagnosed after mild trauma. This case suggests that flap dislocations can occur during recreational activities up to 10 years after surgery. Full visual recovery is achievable if the case is managed promptly. Further studies should evaluate the potential protective role of an inferior hinge during LASIK.