Fivebranes and 4-manifolds

We describe rules for building 2d theories labeled by 4-manifolds. Using the proposed dictionary between building blocks of 4-manifolds and 2d N=(0,2) theories, we obtain a number of results, which include new 3d N=2 theories T[M_3] associated with rational homology spheres and new results for Vafa-Witten partition functions on 4-manifolds. In particular, we point out that the gluing measure for the latter is precisely the superconformal index of 2d (0,2) vector multiplet and relate the basic building blocks with coset branching functions. We also offer a new look at the fusion of defect lines / walls, and a physical interpretation of the 4d and 3d Kirby calculus as dualities of 2d N=(0,2) theories and 3d N=2 theories, respectivelyComment: 81 pages, 18 figures. v2: misprints corrected, clarifications and references added. v3: additions and corrections about lens space theory, 4-manifold gluing, smooth structure

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

Performance Measurement, Development Indicators and Aboriginal Economic Development

This report defines the language of outcomes, indicators, and performance measures and then summarizes a review of applications of several strategies and tools for tracking progress that have been developed since the late 80s. It then reviews the current performance measurement practice of Indian and Northern Affairs at the policy, program, intermediary, and community level. The results demonstrate a confused, wholly inadequate approach to the application of indicators and performance measures at every level. An important feature of the report is found in the Appendix, which sets out a very preliminary strategy for designing indicators that link the characteristics of best practices in Aboriginal Economic Development to possible indicators relevant to each of the four levels, right from the national policy level to the site of the aboriginal community

An outpatient, ambulant-design, controlled human infection model using escalating doses of Salmonella Typhi challenge delivered in sodium bicarbonate solution.

BACKGROUND: Typhoid fever is a major global health problem, the control of which is hindered by lack of a suitable animal model in which to study Salmonella Typhi infection. Until 1974, a human challenge model advanced understanding of typhoid and was used in vaccine development. We set out to establish a new human challenge model and ascertain the S. Typhi (Quailes strain) inoculum required for an attack rate of 60%-75% in typhoid-naive volunteers when ingested with sodium bicarbonate solution. METHODS: Groups of healthy consenting adults ingested escalating dose levels of S. Typhi and were closely monitored in an outpatient setting for 2 weeks. Antibiotic treatment was initiated if typhoid diagnosis occurred (temperature ≥38°C sustained ≥12 hours or bacteremia) or at day 14 in those remaining untreated. RESULTS: Two dose levels (10(3) or 10(4) colony-forming units) were required to achieve the primary objective, resulting in attack rates of 55% (11/20) or 65% (13/20), respectively. Challenge was well tolerated; 4 of 40 participants fulfilled prespecified criteria for severe infection. Most diagnoses (87.5%) were confirmed by blood culture, and asymptomatic bacteremia and stool shedding of S. Typhi was also observed. Participants who developed typhoid infection demonstrated serological responses to flagellin and lipopolysaccharide antigens by day 14; however, no anti-Vi antibody responses were detected. CONCLUSIONS: Human challenge with a small inoculum of virulent S. Typhi administered in bicarbonate solution can be performed safely using an ambulant-model design to advance understanding of host-pathogen interactions and immunity. This model should expedite development of diagnostics, vaccines, and therapeutics for typhoid control

Intranasal Insulin Reduces White Matter Hyperintensity Progression in Association with Improvements in Cognition and CSF Biomarker Profiles in Mild Cognitive Impairment and Alzheimer’s Disease

Background: Intranasally administered insulin has shown promise in both rodent and human studies in Alzheimer’s disease; however, both effects and mechanisms require elucidation. Objective: We assessed the effects of intranasally administered insulin on white matter health and its association with cognition and cerebral spinal fluid biomarker profiles in adults with mild cognitive impairment or Alzheimer’s disease in secondary analyses from a prior phase 2 clinical trial (NCT01767909). Design: A randomized (1:1) double-blind clinical trial. Setting: Twelve sites across the United States. Participants: Adults with mild cognitive impairment or Alzheimer’s disease. Intervention: Participants received either twice daily placebo or insulin (20 IU Humulin R U-100 b.i.d.) intranasally for 12 months. Seventy-eight participants were screened, of whom 49 (32 men) were enrolled. Measurements: Changes from baseline in global and regional white matter hyperintensity volume and gray matter volume were analyzed and related to changes in cerebral spinal fluid biomarkers, Alzheimer’s Disease Assessment Scale-Cognition, Clinical Disease Rating-Sum of Boxes, Alzheimer’s Disease Cooperative Study–Activities of Daily Living Scale, and a memory composite. Results: The insulin-treated group demonstrated significantly reduced changes in white matter hyperintensity volume in deep and frontal regions after 12 months, with a similar trend for global volume. White matter hyperintensity volume progression correlated with worsened Alzheimer’s disease cerebral spinal fluid biomarker profile and cognitive function; however, patterns of correlations differed by treatment group. Conclusion: Intranasal insulin treatment for 12 months reduced white matter hyperintensity volume progression and supports insulin’s potential as a therapeutic option for Alzheimer’s disease.</jats:p