The origins and development of Zuwīla, Libyan Sahara: an archaeological and historical overview of an ancient oasis town and caravan centre

Zuwīla in southwestern Libya (Fazzān) was one of the most important early Islamic centres in the Central Sahara, but the archaeological correlates of the written sources for it have been little explored. This paper brings together for the first time a detailed consideration of the relevant historical and archaeological data, together with new AMS radiocarbon dates from several key monuments. The origins of the settlement at Zuwīla were pre-Islamic, but the town gained greater prominence in the early centuries of Arab rule of the Maghrib, culminating with the establishment of an Ibāḍī state ruled by the dynasty of the Banū Khaṭṭāb, with Zuwīla its capital. The historical sources and the accounts of early European travellers are discussed and archaeological work at Zuwīla is described (including the new radiocarbon dates). A short gazetteer of archaeological monuments is provided as an appendix. Comparisons and contrasts are also drawn between Zuwīla and other oases of the ash-Sharqiyāt region of Fazzān. The final section of the paper presents a series of models based on the available evidence, tracing the evolution and decline of this remarkable site

Global, regional, and national age-sex-specific mortality and life expectancy, 1950–2017: a systematic analysis for the Global Burden of Disease Study 2017

BACKGROUND: Assessments of age-specific mortality and life expectancy have been done by the UN Population Division, Department of Economics and Social Affairs (UNPOP), the United States Census Bureau, WHO, and as part of previous iterations of the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD). Previous iterations of the GBD used population estimates from UNPOP, which were not derived in a way that was internally consistent with the estimates of the numbers of deaths in the GBD. The present iteration of the GBD, GBD 2017, improves on previous assessments and provides timely estimates of the mortality experience of populations globally. METHODS: The GBD uses all available data to produce estimates of mortality rates between 1950 and 2017 for 23 age groups, both sexes, and 918 locations, including 195 countries and territories and subnational locations for 16 countries. Data used include vital registration systems, sample registration systems, household surveys (complete birth histories, summary birth histories, sibling histories), censuses (summary birth histories, household deaths), and Demographic Surveillance Sites. In total, this analysis used 8259 data sources. Estimates of the probability of death between birth and the age of 5 years and between ages 15 and 60 years are generated and then input into a model life table system to produce complete life tables for all locations and years. Fatal discontinuities and mortality due to HIV/AIDS are analysed separately and then incorporated into the estimation. We analyse the relationship between age-specific mortality and development status using the Socio-demographic Index, a composite measure based on fertility under the age of 25 years, education, and income. There are four main methodological improvements in GBD 2017 compared with GBD 2016: 622 additional data sources have been incorporated; new estimates of population, generated by the GBD study, are used; statistical methods used in different components of the analysis have been further standardised and improved; and the analysis has been extended backwards in time by two decades to start in 1950. FINDINGS: Globally, 18·7% (95% uncertainty interval 18·4–19·0) of deaths were registered in 1950 and that proportion has been steadily increasing since, with 58·8% (58·2–59·3) of all deaths being registered in 2015. At the global level, between 1950 and 2017, life expectancy increased from 48·1 years (46·5–49·6) to 70·5 years (70·1–70·8) for men and from 52·9 years (51·7–54·0) to 75·6 years (75·3–75·9) for women. Despite this overall progress, there remains substantial variation in life expectancy at birth in 2017, which ranges from 49·1 years (46·5–51·7) for men in the Central African Republic to 87·6 years (86·9–88·1) among women in Singapore. The greatest progress across age groups was for children younger than 5 years; under-5 mortality dropped from 216·0 deaths (196·3–238·1) per 1000 livebirths in 1950 to 38·9 deaths (35·6–42·83) per 1000 livebirths in 2017, with huge reductions across countries. Nevertheless, there were still 5·4 million (5·2–5·6) deaths among children younger than 5 years in the world in 2017. Progress has been less pronounced and more variable for adults, especially for adult males, who had stagnant or increasing mortality rates in several countries. The gap between male and female life expectancy between 1950 and 2017, while relatively stable at the global level, shows distinctive patterns across super-regions and has consistently been the largest in central Europe, eastern Europe, and central Asia, and smallest in south Asia. Performance was also variable across countries and time in observed mortality rates compared with those expected on the basis of development. INTERPRETATION: This analysis of age-sex-specific mortality shows that there are remarkably complex patterns in population mortality across countries. The findings of this study highlight global successes, such as the large decline in under-5 mortality, which reflects significant local, national, and global commitment and investment over several decades. However, they also bring attention to mortality patterns that are a cause for concern, particularly among adult men and, to a lesser extent, women, whose mortality rates have stagnated in many countries over the time period of this study, and in some cases are increasing

Whole-genome sequencing reveals host factors underlying critical COVID-19

Critical COVID-19 is caused by immune-mediated inflammatory lung injury. Host genetic variation influences the development of illness requiring critical care1 or hospitalization2,3,4 after infection with SARS-CoV-2. The GenOMICC (Genetics of Mortality in Critical Care) study enables the comparison of genomes from individuals who are critically ill with those of population controls to find underlying disease mechanisms. Here we use whole-genome sequencing in 7,491 critically ill individuals compared with 48,400 controls to discover and replicate 23 independent variants that significantly predispose to critical COVID-19. We identify 16 new independent associations, including variants within genes that are involved in interferon signalling (IL10RB and PLSCR1), leucocyte differentiation (BCL11A) and blood-type antigen secretor status (FUT2). Using transcriptome-wide association and colocalization to infer the effect of gene expression on disease severity, we find evidence that implicates multiple genes—including reduced expression of a membrane flippase (ATP11A), and increased expression of a mucin (MUC1)—in critical disease. Mendelian randomization provides evidence in support of causal roles for myeloid cell adhesion molecules (SELE, ICAM5 and CD209) and the coagulation factor F8, all of which are potentially druggable targets. Our results are broadly consistent with a multi-component model of COVID-19 pathophysiology, in which at least two distinct mechanisms can predispose to life-threatening disease: failure to control viral replication; or an enhanced tendency towards pulmonary inflammation and intravascular coagulation. We show that comparison between cases of critical illness and population controls is highly efficient for the detection of therapeutically relevant mechanisms of disease

Microbiological assays as predictors of the response to periodontal therapy.

Thirty-four patients with periodontal disease each had subgingival plaque samples collected from four sites (one from each quadrant) in their mouths. The relative proportions of spirochaetes, motile rods and cocci were determined using dark field microscopy and the proportion of anaerobic to aerobic microorganisms was calculated after culture. In addition, clinical recordings were made at these sampled sites. The patients then underwent a course of periodontal treatment and were placed on a maintenance programme. The clinical recordings were repeated and the results examined to ascertain if the original microbiological or clinical measurements could have been used to predict the response to therapy. Of the baseline recordings, the initial probing depth, the initial attachment level and the presence of suppuration all showed a positive correlation with the degree of pocket reduction or attachment gain produced by treatment. The percentage of cocci in the subgingival plaque correlated negatively with the treatment response. Suppuration seemed to be associated primarily with the original pocket depth while the percentage of cocci in subgingival plaque showed a true relationship with the amount of attachment gained after periodontal therapy. The significance of this finding is discussed

Histological evaluation of effects produced in alveolar bone following gingival incision with an electrosurgical scalpel

Electrosurgery is defined as the application of electrically generated heat energy to living tissue to alter or destroy it for therapeutic purposes. The tissue damage that results varies with the type of electrosurgery unit used. There are 3 principal types: Electrosection: an undamped fully rectified high frequency alternating current with biterminal application is used, and individual cell dehydration and volatilization result, i.e. tissue damage involves merely the line of incision. Electrocoagulation: a highly or moderately damped unrectified alternating current is applied biterminally, causing tissue necrosis over a fairly well localized area. Electrodesiccation (electrocautery): in which a highly damped monoterminal alternating current is used; it produces coagulation necrosis over a wide area, i.e extends readily to deeper tissues. Gingival incisions were performed distal to each of the 2 lower incisors on 25 adult male guinea pigs. For every animal, electrosection with an electrosurgical scalpel was used on one side, and a conventional scalpel was used on the other. The surgical instruments in all cases were brought into direct contact with periosteum. Five animals were killed at each postoperative period (12, 24, 48, 72, and 96 hr), and sections of the areas of surgery were prepared by standard laboratory procedures. At 12 hr postoperatively there were far more soft tissue necrosis, a more extensive inflammatory reaction, and greater destruction of periosteum after electrosurgery. No significant changes in osteocyte viability were seen after either technique. However by 24 hr, many empty lacunae were observed in the bone associated with electrosurgery, such necrosis being even more extensive by 48 hr. In contrast, only very minor, localized areas devoid of some osteocytes were seen after use of the conventional scalpel. By 96 hr the electrosurgical connective tissue wounds were still lined by coagulum, but repair of the scalpel wounds had begun. The periosteum and bone had the same features that were seen at 48 hr. Throughout the study, no increase in osteoclasts was seen in any section, nor were significant changes in adjacent bone marrow observed