Hard-to-Manipulate Combinatorial Auctions

Mechanism design provides a framework to solve distributed optimization problems in systems of self-interested agents. The combinatorial auction is one such problem, in which there is a set of discrete items to allocate to agents. Unfortunately, recent results suggest that it is impossible to implement reasonable approximations without losing robustness to manipulation. Furthermore, the Vickrey-Clarke-Groves (VCG) mechanism is known to be vulnerable to manipulation when agents can bid under multiple false names. In this paper we relax incentive constraints and require only that useful manipulation be NP-hard. We prove that any tractable approximation algorithm can be made to produce a hard-to-manipulate (VCG-based) mechanism, providing a useful counterpoint to these negative results. We also show that falsename bid manipulation in the VCG is NP-hard.Engineering and Applied Science

A case series of percutaneous tension band wiring technique for fixation of fractures of olecranon and patella

There are several advantages in the treatment of fractures by means of closed reduction. Percutaneous fixation is a type of biological fixation. The aim and objectives of this study are to demonstrate the technique of percutaneous tension band wiring in cases of transverse, non- comminuted olecranon and patella fractures and to decrease the soft tissue dissection, blood loss, chances of infection and to ensure speedy mobilization using the innovative percutaneous fixation technique. This retrospective study includes ten patients of olecranon and ten patients of patella operated by the same surgeon. All patients were operated with percutaneous tension band wiring for olecranon and patella. There were six males and four females with olecranon fractures. There were seven males and three females who suffered patella fractures. The average duration of surgery was 55 minutes and average follow up was 24±6 weeks. The suture removal was done at 2 weeks. All patients had full range of movements at six weeks with significantly improved DASH score and Oxford knee score. None of the patients had any complications. Percutaneous fixation decreases the chances of bleeding secondary to unnecessary soft tissue dissection, thereby decreasing the post-operative morbidity. It also, convincingly, decreases the chances of post-operative infection and promotes early mobilization. Closed reduction with percutaneous fixation is believed to be an innovative, safe, reliable and efficient method of managing these difficult fractures

Surveillance of drug-resistant tuberculosis in the state of Gujarat, India

BACKGROUND: Limited information about the prevalence of drug-resistant tuberculosis (TB) has been reported from India, the country with the world’s highest burden of TB. We conducted a representative state-wide survey in the state of Gujarat (2005 population: 56 million). METHODS: Mycobacterium tuberculosis isolates from a representative sample of new and previously treated smear-positive pulmonary TB (PTB) cases were subjected to drug susceptibility testing (DST) against fi rst-line drugs at a World Health Organization supranational reference laboratory. Isolates found to have at least both isoniazid (INH) and rifampicin (RMP) resistance (i.e., multidrugresistant TB [MDR-TB]) were subjected to second-line DST. RESULTS: Of 1571 isolates from new patients, 1236 (78.7%) were susceptible to all fi rst-line drugs, 173 (11%) had any INH resistance and MDR-TB was found in 37 (2.4%, 95%CI 1.6–3.1). Of 1047 isolates from previously treated patients, 564 (54%) were susceptible to all fi rst-line drugs, 387 (37%) had any INH resistance and MDR-TB was found in 182 (17.4%, 95%CI 15.0–19.7%). Among 216 MDR-TB isolates, 52 (24%) were ofl oxacin (OFX) resistant; seven cases of extensively drug-resistant TB (XDR-TB) were found, all of whom were previously treated cases. CONCLUSION: MDR-TB prevalence remains low among new TB patients in Gujarat, but is more common among previously treated patients. Among MDR-TB isolates, the alarmingly high prevalence of OFX resistance may threaten the success of the expanding efforts to treat and control MDR-TB

Comprehensive serial molecular profiling of an “N of 1” exceptional non-responder with metastatic prostate cancer progressing to small cell carcinoma on treatment

Abstract Importance Small cell carcinoma/neuroendocrine prostate cancer (NePC) is a lethal, poorly understood prostate cancer (PCa) subtype. Controversy exists about the origin of NePC in this setting. Objective To molecularly profile archived biopsy specimens from a case of early-onset PCa that rapidly progressed to NePC to identify drivers of the aggressive course and mechanisms of NePC origin and progression. Design, setting, and participants A 47-year-old patient presented with metastatic prostatic adenocarcinoma (Gleason score 9). After a 6-month response to androgen deprivation therapy, the patient developed jaundice and liver biopsy revealed exclusively NePC. Targeted next generation sequencing (NGS) from formalin-fixed paraffin-embedded (FFPE)-isolated DNA was performed from the diagnostic prostate biopsy and the liver biopsy at progression. Intervention Androgen deprivation therapy for adenocarcinoma followed by multiagent chemotherapy for NePC. Main outcomes and measures Identification of the mutational landscape in primary adenocarcinoma and NePC liver metastasis. Whether the NePC arose independently or was derived from the primary adenocarcinoma was considered based on mutational profiles. Results A deleterious somatic SMAD4 L535fs variant was present in both prostate and liver specimens; however, a TP53 R282W mutation was exclusively enriched in the liver specimen. Copy number analysis identified concordant, low-level alterations in both specimens, with focal MYCL amplification and homozygous PTEN, RB1, and MAP2K4 losses identified exclusively in the NePC specimen. Integration with published genomic profiles identified MYCL as a recurrently amplified in NePC. Conclusions and relevance NGS of routine biopsy samples from an exceptional non-responder identified SMAD4 as a driver of the aggressive course and supports derivation of NePC from primary adenocarcinoma (transdifferentiation).http://deepblue.lib.umich.edu/bitstream/2027.42/113670/1/13045_2015_Article_204.pd

Right ventricular shape and function: cardiovascular magnetic resonance reference morphology and biventricular risk factor morphometrics in UK Biobank

Background The associations between cardiovascular disease (CVD) risk factors and the biventricular geometry of the right ventricle (RV) and left ventricle (LV) have been difficult to assess, due to subtle and complex shape changes. We sought to quantify reference RV morphology as well as biventricular variations associated with common cardiovascular risk factors. Methods A biventricular shape atlas was automatically constructed using contours and landmarks from 4329 UK Biobank cardiovascular magnetic resonance (CMR) studies. A subdivision surface geometric mesh was customized to the contours using a diffeomorphic registration algorithm, with automatic correction of slice shifts due to differences in breath-hold position. A reference sub-cohort was identified consisting of 630 participants with no CVD risk factors. Morphometric scores were computed using linear regression to quantify shape variations associated with four risk factors (high cholesterol, high blood pressure, obesity and smoking) and three disease factors (diabetes, previous myocardial infarction and angina). Results The atlas construction led to an accurate representation of 3D shapes at end-diastole and end-systole, with acceptable fitting errors between surfaces and contours (average error less than 1.5 mm). Atlas shape features had stronger associations than traditional mass and volume measures for all factors (p < 0.005 for each). High blood pressure was associated with outward displacement of the LV free walls, but inward displacement of the RV free wall and thickening of the septum. Smoking was associated with a rounder RV with inward displacement of the RV free wall and increased relative wall thickness. Conclusion Morphometric relationships between biventricular shape and cardiovascular risk factors in a large cohort show complex interactions between RV and LV morphology. These can be quantified by z-scores, which can be used to study the morphological correlates of disease

Modelling net-zero emissions energy systems requires a change in approach

Energy modelling can assist national decision makers in determining strategies that achieve net-zero greenhouse gas (GHG) emissions. However, three key challenges for the modelling community are emerging under this radical climate target that needs to be recognized and addressed. A first challenge is the need to represent new mitigation options not currently represented in many energy models. We emphasize here the under representation of end-use sector demand-side options due to the traditional supply side focus of many energy models, along with issues surrounding robustness in deploying carbon dioxide removal (CDR) options. A second challenge concerns the types of models used. We highlight doubts about whether current models provide sufficient relevant insights on system feasibility, actor behaviour, and policy effectiveness. A third challenge concerns how models are applied for policy analyses. Priorities include the need for expanding scenario thinking to incorporate a wider range of uncertainty factors, providing insights on target setting, alignment with broader policy objectives, and improving engagement and transparency of approaches. There is a significant risk that without reconsidering energy modelling approaches, the role that the modelling community can play in providing effective decision support may be reduced. Such support is critical, as countries seek to develop new Nationally Determined Contributions and longer-term strategies over the next few years