Project description:ObjectiveDespite a multitude of detection and treatment advances in the past 2 decades, prostate cancer remains the second leading cause of deaths due to cancer among men in the United States. Technological evolution and expanding knowledge of tumor biomarkers have invigorated exploration in prostate cancer therapeutics. Prostate-specific membrane antigen (PSMA) was one of the first prostate cancer biomarkers successfully cloned. Since then, it has been characterized as the prototypical cell-surface marker for prostate cancer and has been the subject of intense clinical inquiry. In this article, we review the relevant research in PSMA on the 20th anniversary of its cloning.Methods and materialsA PubMed search using the keywords "prostate-specific membrane antigen" or "glutamate carboxypeptidase II" provided 1019 results. An additional 3 abstracts were included from scientific meetings. Articles were vetted by title and abstract with emphasis placed on those with clinically relevant findings.ResultsSixty articles were selected for inclusion. PSMA was discovered and cloned in 1993. Its structure and function were further delineated in the ensuing decade. Consensus sites of expression in normal physiology are prostate, kidney, nervous system, and small intestine. PSMA has been implicated in the neovasculature of several tumors including urothelial and renal cell carcinomas. In prostate cancer, expression of PSMA is directly related to the Gleason grade. PSMA has been tested both in imaging and therapeutics in a number of prostate cancer clinical trials. Several recent approaches to target PSMA include the use of small molecule inhibitors, PSMA-based immunotherapy, RNA aptamer conjugates, and PSMA-targeted prodrug therapy. Future study of PSMA in prostate cancer might focus on its intracellular functions and possible role in tumor neurogenesis.ConclusionsTwenty years from its discovery, PSMA represents a viable biomarker and treatment target in prostate cancer. Research to delineate its precise role in prostate carcinogenesis and within the therapeutic armamentarium for patients with prostate cancer remains encouraging.
Project description:BackgroundCanada was one of the first countries to regulate the medical use of cannabis. However, literature on Canada's medical cannabis program is limited.MethodsWe use administrative data from the medical cannabis program, and licensed cannabis vendor catalog data to describe a) the participation of patients, physicians, and cannabis vendors in the program from its inception in 1999 to 2021, and b) trends in medical cannabis consumption, prices and potency. We also use national surveys conducted over the last several decades to estimate trends in regular cannabis use (medical or otherwise) and how it changed during the medical cannabis access regimes.ResultsIn 2001, the Canadian government granted access to those with physician-documented evidence of a severe health problem that could not be managed using conventional therapies. Most patients accessed cannabis grown under a personal production license. By 2013, authorized daily cannabis dosages were very high. In 2014, the government, concerned over illegal diversion, required that cannabis be purchased from a licensed commercial grower; personal production was banned. Physicians were given responsibility for authorizing patient access. To fill the regulatory void, the physician regulatory bodies in Canada imposed their own prescribing restrictions. After these changes, the number of physicians who were willing to support patient cannabis use markedly decline but the number of patients participating in the program sharply increased. Medical cannabis use varied by province-rates were generally lower in provinces with stricter regulations on physician cannabis prescribing. Most varieties of cannabis oil available for sale are now high in CBD and low in THC. Dry cannabis varieties, conversely, tend to be high in THC and low in CBD. Inflation adjusted prices of most varieties of medical cannabis have declined over time. We find that rates of daily cannabis use (medical or otherwise) increased markedly after the 2014 policy regime. The fraction of Canadians using cannabis daily increased again after the 2018 legalization of recreational cannabis; at the same time, participation in the medical access program declined.ConclusionThe implications for patient health outcomes of changes in the medical cannabis program and legalization of recreational use remains an important area for future research.
Project description:BackgroundPatients with low-grade gliomas (LGG), which are the most common childhood brain tumors, have excellent long-term survival. Dissemination of LGG is rare. Robust data on the incidence, presentation, patterns of dissemination, disease behavior, outcome, and best-management approaches do not exist. We describe 20 years of follow-up of children with metastatic LGG.ProcedureData collected during the period 1990-2010 were retrospectively reviewed for the following inclusion criteria: diagnosis of metastatic LGG, age younger than 21 years at initial diagnosis, and magnetic resonance imaging of the brain and/or spine at diagnosis and/or follow-up. Patient demographics, pathology, treatment modalities, and outcome were reviewed.ResultsOf 599 patients with LGG, 38 (6%) had metastatic disease at either diagnosis or follow-up. Most tumors (87%) were located in the brain, and half of the patients had metastatic disease at presentation. The most common diagnosis was pilocytic astrocytoma (55%). Chemotherapy was the most common initial treatment modality. Median survival of the group was 6.2 years (range, 0.1-16.9 years). Fifteen (40%) patients died at a median of 6 years from diagnosis (range, 0.8-15 years). Overall survival at 5, 10, and 15 years was 80.7 ± 6.6%, 63.0 ± 10.2%, and 50.9 ± 16.0%, respectively.ConclusionThis study describes the longest follow-up of children with metastatic LGG. LGG is underestimated and entails major morbidity and mortality. Prospective studies are needed to learn the true incidence, study the biology, and determine the best approaches to diagnosis, treatment, and follow-up.
Project description:The International Society for Stem Cell Research (ISSCR) celebrates its 20th anniversary in 2022. This review looks back at some of the key developments in stem cell research as well as the evolution of the ISSCR as part of that field. Important discoveries from stem cell research are described, and how the improved understanding of basic stem cell biology translates into new clinical therapies and insights into disease mechanisms is discussed. Finally, the birth and growth of ISSCR into a leading stem cell society and a respected voice for ethics, advocacy, education and policy in stem cell research are described.
Project description:What are desirable and undesirable features of virtual-environment (VE) software architectures? What should be present (and absent) from such systems if they are to be optimally useful? How should they be structured? To help answer these questions we present experience from application designers, toolkit designers, and VE system architects along with examples of useful features from existing systems. Topics are organized under the major headings of: 3D space management, supporting display hardware, interaction, event management, time management, computation, portability, and the observation that less can be better. Lessons learned are presented as discussion of the issues, field experiences, nuggets of knowledge, and case studies.
Project description:BackgroundPrevalence of self-reported domestic violence against women in India is high. This paper investigates the national and sub-national trends in domestic violence in India to prioritise prevention activities and to highlight the limitations to data quality for surveillance in India.MethodsData were extracted from annual reports of National Crimes Record Bureau (NCRB) under four domestic violence crime-headings-cruelty by husband or his relatives, dowry death, abetment to suicide, and protection of women against domestic violence act. Rate for each crime is reported per 100,000 women aged 15-49 years, for India and its states from 2001 to 2018. Data on persons arrested and legal status of the cases were extracted.ResultsRate of reported cases of cruelty by husband or relatives in India was 28.3 (95% CI 28.1-28.5) in 2018, an increase of 53% from 2001. State-level variations in this rate ranged from 0.5 (95% CI - 0.05 to 1.5) to 113.7 (95% CI 111.6-115.8) in 2018. Rate of reported dowry deaths and abetment to suicide was 2.0 (95% CI 2.0-2.0) and 1.4 (95% CI 1.4-1.4) in 2018 for India, respectively. Overall, a few states accounted for the temporal variation in these rates, with the reporting stagnant in most states over these years. The NCRB reporting system resulted in underreporting for certain crime-headings. The mean number of people arrested for these crimes had decreased over the period. Only 6.8% of the cases completed trials, with offenders convicted only in 15.5% cases in 2018. The NCRB data are available in heavily tabulated format with limited usage for intervention planning. The non-availability of individual level data in public domain limits exploration of patterns in domestic violence that could better inform policy actions to address domestic violence.ConclusionsUrgent actions are needed to improve the robustness of NCRB data and the range of information available on domestic violence cases to utilise these data to effectively address domestic violence against women in India.
Project description:The Japanese term hikikomori was first used to describe prolonged social withdrawal in the 1990s. Since then, research across the world have reported similar prolonged social withdrawal in many countries outside Japan. This study systematically analyses the evolution of literature on hikikomori in the past 20 years to gain a better understanding of the development of the knowledge base on hikikomori since it garnered attention in Japan. Findings from the scientometric review indicate many perspectives on the etiology of hikikomori including cultural, attachment, family systems and sociological approaches. However, similarities with modern type depression, a novel psychiatric syndrome, have been proposed and there are signs of a recent paradigm shift of hikikomori as a society-bound syndrome rather than a cultural-bound syndrome unique to Japan. As research into hikikomori continues to grow, results from the review also highlight the need for a more universally shared definition of hikikomori in order to better consolidate cross-cultural research for meaningful and valid cross-cultural comparisons which can help to promote evidence-based therapeutic interventions for hikikomori.
Project description:BackgroundThis study aimed to discuss and report the trend, outcomes, and learning curve effect after minimally invasive distal pancreatectomy (MIDP) at two high-volume centres.MethodsPatients undergoing MIDP between January 1999 and December 2018 were retrospectively identified from prospectively maintained electronic databases. The entire cohort was divided into two groups constituting the "early" and "recent" phases. The learning curve effect was analyzed for laparoscopic (LDP) and robotic distal pancreatectomy (RDP). The follow-up was at least 2 years.ResultsThe study population included 401 consecutive patients (LDP n = 300, RDP n = 101). Twelve surgeons performed MIDP during the study period. Although patients were more carefully selected in the early phase, in terms of median age (49 vs. 55 years, p = 0.026), ASA class higher than 2 (3% vs. 9%, p = 0.018), previous abdominal surgery (10% vs. 34%, p < 0.001), and pancreatic adenocarcinoma (PDAC) (7% vs. 15%, p = 0.017), the recent phase had similar perioperative outcomes. The increase of experience in LDP was inversely associated with the operative time (240 vs 210 min, p < 0.001), morbidity rate (56.5% vs. 40.1%, p = 0.005), intra-abdominal collection (28.3% vs. 17.3%, p = 0.023), and length of stay (8 vs. 7 days, p = 0.009). Median survival in the PDAC subgroup was 53 months.ConclusionIn the setting of high-volume centres, the surgical training of MIDP is associated with acceptable rates of morbidity. The learning curve can be largely achieved by several team members, improving outcomes over time. Whenever possible resection of PDAC guarantees adequate oncological results and survival.