Many-Body Delocalization via Emergent Symmetry.

Many-body localization (MBL) provides a mechanism to avoid thermalization in many-body quantum systems. Here, we show that an emergent symmetry can protect a state from MBL. Specifically, we propose a Z_{2} symmetric model with nonlocal interactions, which has an analytically known, SU(2) invariant, critical ground state. At large disorder strength, all states at finite energy density are in a glassy MBL phase, while the lowest energy states are not. These do, however, localize when a perturbation destroys the emergent SU(2) symmetry. The model also provides an example of MBL in the presence of nonlocal, disordered interactions that are more structured than a power law. Finally, we show how the protected state can be moved into the bulk of the spectrum.

Multimodal intraoperative neuromonitoring in scoliosis surgery: A two-year prospective analysis in a single centre.

AIM: The present study is a prospective analysis of neuromonitoring [somatosensory evoked potentials (SSEP) and transcranial motor evoked potentials (TcMEP)] in consecutive scoliosis surgeries done at a tertiary care spine centre. MATERIALS AND METHODS: Prospective analysis was performed on 52 consecutive patients undergoing scoliosis correction from 2013 to 2015. SSEPs were obtained by stimulating the median and tibial nerves with stimulus intensity level 20-25 mA. TcMEPs were recorded bilaterally from abductor pollicis brevis, biceps, and deltoid for the upper limb, and from tibialis anterior, quadriceps, gastrocnemius, and abductor hallucis for the lower limb. Stimulation was given in the form of a high voltage (300-400 V) stimulus. An "alert" was defined as reduction in the amplitude of at least 50% for SSEP and at least 65% for TcMEP compared to the baseline recordings and an increase in the latency by more than 10%. RESULTS: The mean age of the patients was 14.6 years (7-33 years). Thirty-nine of the patients were females and 13 were males. Baseline values in neuromuscular scoliosis were low compared to adolescent idiopathic scoliosis (AIS). There were no false negative incidents. False positive cases were due to low blood pressure and malfunctioning of the leads. CONCLUSION: Use of upper limb leads could help in identifying malposition or malfunctioning of leads to eliminate false positive results. Combined multimodal intraoperative monitoring helps in increasing the safety in scoliosis corrective surgeries with a high sensitivity and specificity. Baseline values in neuromuscular scoliosis patients are possibly lower than idiopathic scoliosis patients. Intraoperative variations must be interpreted with caution.

Whole-exome sequencing of Indian prostate cancer reveals a novel therapeutic target: POLQ.

PURPOSE: Prostate cancer is the second most common cancer diagnosed worldwide and the third most common cancer among men in India. This study's objective was to characterise the mutational landscape of Indian prostate cancer using whole-exome sequencing to identify population-specific polymorphisms. METHODS: Whole-exome sequencing was performed of 58 treatment-naive primary prostate tumors of Indian origin. Multiple computational and statistical analyses were used to profile the known common mutations, other deleterious mutations, driver genes, prognostic biomarkers, and gene signatures unique to each clinical parameter. Cox analysis was performed to validate survival-associated genes. McNemar test identified genes significant to recurrence and receiver-operating characteristic (ROC) analysis was conducted to determine its accuracy. OncodriveCLUSTL algorithm was used to deduce driver genes. The druggable target identified was modeled with its known inhibitor using Autodock. RESULTS: TP53 was the most commonly mutated gene in our cohort. Three novel deleterious variants unique to the Indian prostate cancer subtype were identified: POLQ, FTHL17, and OR8G1. COX regression analysis identified ACSM5, a mitochondrial gene responsible for survival. CYLC1 gene, which encodes for sperm head cytoskeletal protein, was identified as an unfavorable prognostic biomarker indicative of recurrence. The novel POLQ mutant, also identified as a driver gene, was evaluated as the druggable target in this study. POLQ, a DNA repair enzyme implicated in various cancer types, is overexpressed and is associated with a poor prognosis. The mutant POLQ was subjected to structural analysis and modeled with its known inhibitor novobiocin resulting in decreased binding efficiency necessitating the development of a better drug. CONCLUSION: In this pilot study, the molecular profiling using multiple computational and statistical analyses revealed distinct polymorphisms in the Indian prostate cancer cohort. The mutational signatures identified provide a valuable resource for prognostic stratification and targeted treatment strategies for Indian prostate cancer patients. The DNA repair enzyme, POLQ, was identified as the druggable target in this study.

Outcomes of Minimally Invasive Radical Prostatectomy-a Contemporary Review.

Prostatectomy has been widely accepted as a treatment option for prostate cancer and can be performed via an open, laparoscopic, and robotic approach. The outcomes following prostatectomy are primarily sub-grouped into oncological and functional outcomes. Oncological outcomes have been comparable in the above three surgical modalities. However, the robotic platform seems to have a better functional outcome compared to open prostatectomy. The data on the outcome of the laparoscopic approach is scarce and is not widely performed due to technical difficulty. With experience continence outcomes have reached a plateau in many robotic series, however, the potency outcome is the real Achilles tendon of this procedure. Many factors influence potency outcomes but the amount and quality of nerve-sparing is one factor that is under a surgeon's control and it improves with experience.

Role of RPLND and Metastasectomy in the Management of Oligometastatic Renal Cell Carcinoma.

Although lymphadenectomy is currently accepted as most accurate and reliable staging procedure for lymph node metastases, its therapeutic benefit in renal cell carcinoma (RCC) still remains controversial. Although the new, targeted therapy paradigms have changed the treatment of patients with advanced RCC and offer prolonged survival, cure is extremely uncommon in the absence of surgical resections. In this paper, the current role of metastasectomy is reviewed. Review the available literature concerning the role of retroperitoneal lymph node dissection and metastasectomy in outcome of oligometastatic RCC. A PubMed search was conducted to identify original articles, review articles, and editorials addressing the role of retroperitoneal lymph node dissection and metastasectomy in outcome of oligometastatic RCC. Keywords included renal tumors, renal cell cancer, kidney cancer, lymphadenectomy, metastasectomy, and oligometastases. While there is no randomized study available, recent large observational studies have better defined the prognosis of patients with metastatic RCC with or without metastasectomy and RPLND. To date, the available evidence suggests that RPLND and metastasectomy may be beneficial when technically feasible in patients with locally advanced (unfavorable clinical and pathologic characteristics) and oligometastatic disease. A proportion of patients will achieve long-term survival with aggressive surgical resection.

VEIL Surgical Steps.

Inguinal lymphadenectomy remains the standard of care for metastatic nodal disease in cases of penile, urethral, vulval and vaginal cancers. Outcomes, including cure rates and overall and progression-free survivals, have progressively improved in these diseases with extending criteria to offer inguinal lymph node dissection for patients 'at-risk' for metastasis or loco-regional recurrence. Hence, despite declining incidence of advanced stages of these cancers, many patients will still need to undergo lymphadenectomy for optimal oncological outcomes. Inguinal node dissection is a morbid procedure with operative morbidity noted in almost two third of the patients. Video endoscopic inguinal lymphadenectomy (VEIL) was described and currently practiced with proven equivalent oncological outcomes. We describe our technique of VEIL using laparoscopic and robotic access as well as various new surgical strategies.

Radical Prostatectomy for Locally Advanced Prostate Cancers-Review of Literature.

Twenty-five to thirty percent of patients with prostate cancer present with locally advanced disease. While risk stratification remains the same with high incidence of upstaging of disease on imaging and histopathological evaluation; there have been progressive refinements in surgical therapy. With availability of reasonably robust data, radical prostatectomy in men with locally advanced prostate cancers seems to effect improvement in both cancer specific and overall survival rates in comparison to the current standard of care of radiation with androgen deprivation therapy. Studies using radical prostatectomy as a part of multimodality approach have also shown promising results. There is an imminent need for well-designed prospective studies of benefits of radical prostatectomy over radiation and androgen deprivation as well as benefits of multimodality therapy over monotherapy. Surgery for patients with locally advanced prostate cancer is technically challenging. Surgical outcomes are comparable to those of organ-confined disease when performed in high-volume centers. Neoadjuvant therapies prior to radical prostatectomy might improve surgical outcomes, but whether they will translate into a better cancer specific and overall survival are yet to be ascertained.

GnRH Antagonist: a New and an Effective Way of Treatment of Advanced Prostate Cancer.

Castration remains the mainstay of treatment in the management of metastatic prostate cancer. Medical castration plays an important role in a majority of these patients. Gonadotropin releasing hormone (GnRH) agonists have been commonly used hitherto to achieve medical castration. Arrival of GnRH antagonists have opened a new approach in the management of these patients with distinct drug-related and cancer-related benefits including prevention of microsurges and reduction in cardiovascular complications. This article elucidates the mechanism of action of GnRH antagonists along with its clinical advantages and demerits.