Privacy and Truthful Equilibrium Selection for Aggregative Games

We study a very general class of games --- multi-dimensional aggregative games --- which in particular generalize both anonymous games and weighted congestion games. For any such game that is also large, we solve the equilibrium selection problem in a strong sense. In particular, we give an efficient weak mediator: a mechanism which has only the power to listen to reported types and provide non-binding suggested actions, such that (a) it is an asymptotic Nash equilibrium for every player to truthfully report their type to the mediator, and then follow its suggested action; and (b) that when players do so, they end up coordinating on a particular asymptotic pure strategy Nash equilibrium of the induced complete information game. In fact, truthful reporting is an ex-post Nash equilibrium of the mediated game, so our solution applies even in settings of incomplete information, and even when player types are arbitrary or worst-case (i.e. not drawn from a common prior). We achieve this by giving an efficient differentially private algorithm for computing a Nash equilibrium in such games. The rates of convergence to equilibrium in all of our results are inverse polynomial in the number of players $n$. We also apply our main results to a multi-dimensional market game. Our results can be viewed as giving, for a rich class of games, a more robust version of the Revelation Principle, in that we work with weaker informational assumptions (no common prior), yet provide a stronger solution concept (ex-post Nash versus Bayes Nash equilibrium). In comparison to previous work, our main conceptual contribution is showing that weak mediators are a game theoretic object that exist in a wide variety of games -- previously, they were only known to exist in traffic routing games

A Phase 1 study of ADI-PEG20 (pegargiminase) combined with cisplatin and pemetrexed in ASS1-negative metastatic uveal melanoma

Metastatic uveal melanoma (UM) is a devastating disease with few treatment options. We evaluated the safety, tolerability and preliminary activity of arginine depletion using pegylated arginine deiminase (ADI‐PEG20; pegargiminase) combined with pemetrexed (Pem) and cisplatin (Cis) chemotherapy in a phase 1 dose‐expansion study of patients with argininosuccinate synthetase (ASS1)‐deficient metastatic UM. Eligible patients received up to six cycles of Pem (500 mg/m(2)) and Cis (75 mg/m(2)) every 3 weeks plus weekly intramuscular ADI (36 mg/m(2)), followed by maintenance ADI until progression (NCT02029690). Ten of fourteen ASS1‐deficient patients with UM liver metastases and a median of one line of prior immunotherapy received ADIPemCis. Only one ≥ grade 3 adverse event of febrile neutropenia was reported. Seven patients had stable disease with a median progression‐free survival of 3.0 months (range, 1.3–8.1) and a median overall survival of 11.5 months (range, 3.2–36.9). Despite anti‐ADI‐PEG20 antibody emergence, plasma arginine concentrations remained suppressed by 18 weeks with a reciprocal increase in plasma citrulline. Tumour rebiopsies at progression revealed ASS1 re‐expression as an escape mechanism. ADIPemCis was well tolerated with modest disease stabilisation in metastatic UM. Further investigation of arginine deprivation is indicated in UM including combinations with immune checkpoint blockade and additional anti‐metabolite strategies

Lateral Gene Expression in Drosophila Early Embryos Is Supported by Grainyhead-Mediated Activation and Tiers of Dorsally-Localized Repression

The general consensus in the field is that limiting amounts of the transcription factor Dorsal establish dorsal boundaries of genes expressed along the dorsal-ventral (DV) axis of early Drosophila embryos, while repressors establish ventral boundaries. Yet recent studies have provided evidence that repressors act to specify the dorsal boundary of intermediate neuroblasts defective (ind), a gene expressed in a stripe along the DV axis in lateral regions of the embryo. Here we show that a short 12 base pair sequence (“the A-box”) present twice within the ind CRM is both necessary and sufficient to support transcriptional repression in dorsal regions of embryos. To identify binding factors, we conducted affinity chromatography using the A-box element and found a number of DNA-binding proteins and chromatin-associated factors using mass spectroscopy. Only Grainyhead (Grh), a CP2 transcription factor with a unique DNA-binding domain, was found to bind the A-box sequence. Our results suggest that Grh acts as an activator to support expression of ind, which was surprising as we identified this factor using an element that mediates dorsally-localized repression. Grh and Dorsal both contribute to ind transcriptional activation. However, another recent study found that the repressor Capicua (Cic) also binds to the A-box sequence. While Cic was not identified through our A-box affinity chromatography, utilization of the same site, the A-box, by both factors Grh (activator) and Cic (repressor) may also support a “switch-like” response that helps to sharpen the ind dorsal boundary. Furthermore, our results also demonstrate that TGF-β signaling acts to refine ind CRM expression in an A-box independent manner in dorsal-most regions, suggesting that tiers of repression act in dorsal regions of the embryo

Structural and Functional Changes of the Human Macula during Acute Exposure to High Altitude

Background: This study aimed to quantify structural and functional changes at the macula during acute exposure to high altitude and to assess their structure/function relationship. This work is related to the Tuebingen High Altitude Ophthalmology (THAO) study. Methodology/Principal Findings: Spectral domain optical coherence tomography and microperimetry were used to quantify changes of central retinal structure and function in 14 healthy subjects during acute exposure to high altitude (4559 m). High-resolution volume scans and fundus-controlled microperimetry of the posterior pole were performed in addition to best-corrected visual acuity (BCVA) measurements and assessment of acute mountain sickness. Analysis of measurements at altitude vs. baseline revealed increased total retinal thickness (TRT) in all four outer ETDRS grid subfields during acute altitude exposure (TRTouter = 2.8061.00 mm; mean change695%CI). This change was inverted towards the inner four subfields (TRT inner = 21.8960.97 mm) with significant reduction of TRT in the fovea (TRT foveal = 26.6260.90 mm) at altitude. BCVA revealed no significant difference compared to baseline (0.0660.08 logMAR). Microperimetry showed stable mean sensitivity in all but the foveal subfield (MSfoveal = 21.1260.68 dB). At baseline recordings before and.2 weeks after high altitude exposure, all subjects showed equal levels with no sign of persisting structural or functional sequels. Conclusions/Significance: During acute exposure to high altitude central retinal thickness is subject to minor, ye

Underweight and overweight men have greater exercise-induced dyspnoea than normal weight men.

INTRODUCTION: Persons with high or low body mass index (BMI), involved in clinical or mechanistic trials involving exercise testing, might estimate dyspnoea differently from persons with a normal BMI. AIMS: Our objective was to investigate the relationship between BMI and dyspnoea during exercise in normal subjects with varying BMI. MATERIAL AND METHODS: A total of 37 subjects undertook progressive exercise testing. Subjects were divided into three groups: underweight (UW), normal weight (NW), and overweight (OW). Dyspnoea was estimated using the visual analogue scale (VAS). Spirometry, maximum voluntary ventilation (MVV), and respiratory muscle strength (RMS) were measured. RESULTS AND DISCUSSION: The intercept of the VAS/ventilation relationship was significantly higher in NW subjects compared to UW (P = 0.029) and OW subjects (P = 0.040). Relative to the OW group, FVC (P = 0.020), FEV(1) (P = 0.024), MVV (P = 0.019), and RMS (P = 0.003) were significantly decreased in the UW group. The greater levels of dyspnoea in UW subjects could possibly be due to decreased RMS. Healthy persons should aim to achieve an optimum BMI range to have the lowest exercise-induced dyspnoea

Mapping of Mycobacterium tuberculosis Complex Genetic Diversity Profiles in Tanzania and Other African Countries

The aim of this study was to assess and characterize Mycobacterium tuberculosis complex (MTBC) genotypic diversity in Tanzania, as well as in neighbouring East and other several African countries. We used spoligotyping to identify a total of 293 M. tuberculosis clinical isolates (one isolate per patient) collected in the Bunda, Dar es Salaam, Ngorongoro and Serengeti areas in Tanzania. The results were compared with results in the SITVIT2 international database of the Pasteur Institute of Guadeloupe. Genotyping and phylogeographical analyses highlighted the predominance of the CAS, T, EAI, and LAM MTBC lineages in Tanzania. The three most frequent Spoligotype International Types (SITs) were: SIT21/CAS1-Kili (n = 76; 25.94%), SIT59/LAM11-ZWE (n = 22; 7.51%), and SIT126/EAI5 tentatively reclassified as EAI3-TZA (n = 18; 6.14%). Furthermore, three SITs were newly created in this study (SIT4056/EAI5 n = 2, SIT4057/T1 n = 1, and SIT4058/EAI5 n = 1). We noted that the East-African-Indian (EAI) lineage was more predominant in Bunda, the Manu lineage was more common among strains isolated in Ngorongoro, and the Central-Asian (CAS) lineage was more predominant in Dar es Salaam (p-value<0.0001). No statistically significant differences were noted when comparing HIV status of patients vs. major lineages (p-value = 0.103). However, when grouping lineages as Principal Genetic Groups (PGG), we noticed that PGG2/3 group (Haarlem, LAM, S, T, and X) was more associated with HIV-positive patients as compared to PGG1 group (Beijing, CAS, EAI, and Manu) (p-value = 0.03). This study provided mapping of MTBC genetic diversity in Tanzania (containing information on isolates from different cities) and neighbouring East African and other several African countries highlighting differences as regards to MTBC genotypic distribution between Tanzania and other African countries. This work also allowed underlining of spoligotyping patterns tentatively grouped within the newly designated EAI3-TZA lineage (remarkable by absence of spacers 2 and 3, and represented by SIT126) which seems to be specific to Tanzania. However, further genotyping information would be needed to confirm this specificity

Human leukocyte antigen supertype matching after myeloablative hematopoietic cell transplantation with 7/8 matched unrelated donor allografts: a report from the Center for International Blood and Marrow Transplant Research

The diversity of the human leukocyte antigen (HLA) class I and II alleles can be simplified by consolidating them into fewer supertypes based on functional or predicted structural similarities in epitope-binding grooves of HLA molecules. We studied the impact of matched and mismatched HLA-A (265 versus 429), -B (230 versus 92), -C (365 versus 349), and -DRB1 (153 versus 51) supertypes on clinical outcomes of 1934 patients with acute leukemias or myelodysplasia/myeloproliferative disorders. All patients were reported to the Center for International Blood and Marrow Transplant Research following single-allele mismatched unrelated donor myeloablative conditioning hematopoietic cell transplantation. Single mismatched alleles were categorized into six HLA-A (A01, A01A03, A01A24, A02, A03, A24), six HLA-B (B07, B08, B27, B44, B58, B62), two HLA-C (C1, C2), and five HLA-DRB1 (DR1, DR3, DR4, DR5, DR9) supertypes. Supertype B mismatch was associated with increased risk of grade II-IV acute graft-versus-host disease (hazard ratio =1.78, P=0.0025) compared to supertype B match. Supertype B07-B44 mismatch was associated with a higher incidence of both grade II-IV (hazard ratio=3.11, P=0.002) and III-IV (hazard ratio=3.15, P=0.01) acute graft-versus-host disease. No significant associations were detected between supertype-matched versus -mismatched groups at other HLA loci. These data suggest that avoiding HLA-B supertype mismatches can mitigate the risk of grade II-IV acute graft-versus-host disease in 7/8-mismatched unrelated donor hematopoietic cell transplantation when multiple HLA-B supertype-matched donors are available. Future studies are needed to define the mechanisms by which supertype mismatching affects outcomes after alternative donor hematopoietic cell transplantation

Hypothermia predicts mortality in critically ill elderly patients with sepsis

<p>Abstract</p> <p>Background</p> <p>Advanced age is one of the factors that increase mortality in intensive care. Sepsis and multi-organ failure are likely to further increase mortality in elderly patients.</p> <p>We compared the characteristics and outcomes of septic elderly patients (> 65 years) with younger patients (≤ 65 years) and identified factors during the first 24 hours of presentation that could predict mortality in elderly patients.</p> <p>Methods</p> <p>This study was conducted in a Level III intensive care unit with a case mix of medical and surgical patients excluding cardiac and neurosurgical patients.</p> <p>We performed a retrospective review of all septic patients admitted to our ICU between July 2004 and May 2007. In addition to demographics and co-morbidities, physiological and laboratory variables were analysed to identify early predictors of mortality in elderly patients with sepsis.</p> <p>Results</p> <p>Of 175 patients admitted with sepsis, 108 were older than 65 years. Elderly patients differed from younger patients with regard to sex, temperature (37.2°C VS 37.8°C p < 0.01), heart rate, systolic blood pressure, pH, HCO₃, potassium, urea, creatinine, APACHE III and SAPS II. The ICU and hospital mortality was significantly higher in elderly patients (10.6% Vs 23.14% (p = 0.04) and 19.4 Vs 35.1 (p = 0.02) respectively). Elderly patients who died in hospital had a significant difference in pH, HCO₃, mean blood pressure, potassium, albumin, organs failed, lactate, APACHE III and SAPS II compared to the elderly patients who survived while the mean age and co-morbidities were comparable. Logistic regression analysis identified temperature (OR [per degree centigrade decrease] 0.51; 95% CI 0.306- 0.854; p = 0.010) and SAPS II (OR [per point increase]: 1.12; 95% CI 1.016-1.235; p = 0.02) during the first 24 hours of admission to independently predict increased hospital mortality in elderly patients.</p> <p>Conclusions</p> <p>The mortality in elderly patients with sepsis is higher than the younger patients. Temperature (hypothermia) and SAPS II scores during the first 24 hours of presentation independently predict hospital mortality.</p

Characterization and Optical Properties of the Single Crystalline SnS Nanowire Arrays

The SnS nanowire arrays have been successfully synthesized by the template-assisted pulsed electrochemical deposition in the porous anodized aluminum oxide template. The investigation results showed that the as-synthesized nanowires are single crystalline structures and they have a highly preferential orientation. The ordered SnS nanowire arrays are uniform with a diameter of 50 nm and a length up to several tens of micrometers. The synthesized SnS nanowires exhibit strong absorption in visible and near-infrared spectral region and the direct energy gapEgof SnS nanowires is 1.59 eV