Numerosity, the set size of a group of items, is processed by the association cortex, but certain aspects mirror the properties of primary senses. Sensory cortices contain topographic maps reflecting ...the structure of sensory organs. Are the cortical representation and processing of numerosity organized topographically, even though no sensory organ has a numerical structure? Using high-field functional magnetic resonance imaging (at a field strength of 7 teslas), we described neural populations tuned to small numerosities in the human parietal cortex. They are organized topographically, forming a numerosity map that is robust to changes in low-level stimulus features. The cortical surface area devoted to specific numerosities decreases with increasing numerosity, and the tuning width increases with preferred numerosity. These organizational properties extend topographic principles to the representation of higher-order abstract features in the association cortex.
Before April 2022, monkeypox virus infection in humans was seldom reported outside African regions where it is endemic. Currently, cases are occurring worldwide. Transmission, risk factors, clinical ...presentation, and outcomes of infection are poorly defined.
We formed an international collaborative group of clinicians who contributed to an international case series to describe the presentation, clinical course, and outcomes of polymerase-chain-reaction-confirmed monkeypox virus infections.
We report 528 infections diagnosed between April 27 and June 24, 2022, at 43 sites in 16 countries. Overall, 98% of the persons with infection were gay or bisexual men, 75% were White, and 41% had human immunodeficiency virus infection; the median age was 38 years. Transmission was suspected to have occurred through sexual activity in 95% of the persons with infection. In this case series, 95% of the persons presented with a rash (with 64% having ≤10 lesions), 73% had anogenital lesions, and 41% had mucosal lesions (with 54 having a single genital lesion). Common systemic features preceding the rash included fever (62%), lethargy (41%), myalgia (31%), and headache (27%); lymphadenopathy was also common (reported in 56%). Concomitant sexually transmitted infections were reported in 109 of 377 persons (29%) who were tested. Among the 23 persons with a clear exposure history, the median incubation period was 7 days (range, 3 to 20). Monkeypox virus DNA was detected in 29 of the 32 persons in whom seminal fluid was analyzed. Antiviral treatment was given to 5% of the persons overall, and 70 (13%) were hospitalized; the reasons for hospitalization were pain management, mostly for severe anorectal pain (21 persons); soft-tissue superinfection (18); pharyngitis limiting oral intake (5); eye lesions (2); acute kidney injury (2); myocarditis (2); and infection-control purposes (13). No deaths were reported.
In this case series, monkeypox manifested with a variety of dermatologic and systemic clinical findings. The simultaneous identification of cases outside areas where monkeypox has traditionally been endemic highlights the need for rapid identification and diagnosis of cases to contain further community spread.
The Kuiper Belt of our solar system is a source of short-period comets that may have delivered water and other volatiles to Earth and the other terrestrial planets. However, the distribution of water ...and other volatiles in extrasolar planetary systems is largely unknown. We report the discovery of an accretion of a Kuiper-Belt-Object analog onto the atmosphere of the white dwarf WD 1425+540. The heavy elements C, N, O, Mg, Si, S, Ca, Fe, and Ni are detected, with nitrogen observed for the first time in extrasolar planetary debris. The nitrogen mass fraction is ~2%, comparable to that in comet Halley and higher than in any other known solar system object. The lower limit to the accreted mass is ~10 super(22) g, which is about one hundred thousand times the typical mass of a short-period comet. In addition, WD 1425+540 has a wide binary companion, which could facilitate perturbing a Kuiper-Belt-Object analog into the white dwarf's tidal radius. This finding shows that analogs to objects in our Kuiper Belt exist around other stars and could be responsible for the delivery of volatiles to terrestrial planets beyond the solar system.
Urine is a valuable diagnostic medium and, with the discovery of urinary extracellular vesicles, is viewed as a dynamic bioactive fluid. Extracellular vesicles are lipid-enclosed structures that can ...be classified into three categories: exosomes, microvesicles (or ectosomes) and apoptotic bodies. This classification is based on the mechanisms by which membrane vesicles are formed: fusion of multivesicular bodies with the plasma membranes (exosomes), budding of vesicles directly from the plasma membrane (microvesicles) or those shed from dying cells (apoptotic bodies). During their formation, urinary extracellular vesicles incorporate various cell-specific components (proteins, lipids and nucleic acids) that can be transferred to target cells. The rigour needed for comparative studies has fueled the search for optimal approaches for their isolation, purification, and characterization. RNA, the newest extracellular vesicle component to be discovered, has received substantial attention as an extracellular vesicle therapeutic, and compelling evidence suggests that ex vivo manipulation of microRNA composition may have uses in the treatment of kidney disorders. The results of these studies are building the case that urinary extracellular vesicles act as mediators of renal pathophysiology. As the field of extracellular vesicle studies is burgeoning, this Review focuses on primary data obtained from studies of human urine rather than on data from studies of laboratory animals or cultured immortalized cells.
Infrared studies have revealed debris likely related to planet formation in orbit around {approx}30% of youthful, intermediate mass, main-sequence stars. We present evidence, based on atmospheric ...pollution by various elements heavier than helium, that a comparable fraction of the white dwarf descendants of such main-sequence stars are orbited by planetary systems. These systems have survived, at least in part, through all stages of stellar evolution that precede the white dwarf. During the time interval ({approx}200 million years) that a typical polluted white dwarf in our sample has been cooling it has accreted from its planetary system the mass of one of the largest asteroids in our solar system (e.g., Vesta or Ceres). Usually, this accreted mass will be only a fraction of the total mass of rocky material that orbits these white dwarfs; for plausible planetary system configurations we estimate that this total mass is likely to be at least equal to that of the Sun's asteroid belt, and perhaps much larger. We report abundances of a suite of eight elements detected in the little studied star G241-6 that we find to be among the most heavily polluted of all moderately bright white dwarfs.
The model for end-stage liver disease (MELD) score is used to stratify candidates for liver transplantation based on objective measures of disease severity. MELD has been validated as a predictor of ...wait-list mortality in transplantation candidates and has been postulated as a predictor of post-transplant survival. The purpose of this study was to examine the predictive value of the pre-transplantation MELD score on post-transplant survival from relevant existing studies. A systematic review and critical appraisal was performed using Cochrane guidelines. PubMed, the Cochrane Library, Embase, and Web of Science were searched for articles published in the English language since 2005 using a structured search strategy. There were 3058 discrete citations identified and screened for possible inclusion. Any study examining the relationship between pre-transplant MELD and post-transplant survival in the general transplant population was included. Thirty-seven studies met these criteria and were included in the review. Studies were all case series that typically involved stratified analyses of survival by MELD. They represented 15 countries and a total of 53,691 patients. There was significant clinical heterogeneity in patient populations across studies, which precluded performance of a meta-analysis. In 15 studies, no statistically significant association between MELD and post-transplant survival was found. In the remaining 22, some association was found. Eleven studies also measured predictive ability with c-statistics. Values were below 0.7 in all but two studies, suggesting poor predictive value. In summary, while the majority of studies reported an association between pre-transplantation MELD score and post-transplant survival, they represented a low level of evidence. Therefore, their findings should be interpreted conservatively.
Chromium is a human carcinogen primarily by inhalation exposure in occupational settings. Although lung cancer has been established as a consequence of hexavalent chromium exposure in smokers and ...nonsmokers, some cancers of other tissues of the gastrointestinal and central nervous systems have also been noted. Except for a few reports from China, little is known about the health risks of environmental exposures to chromium. Likewise, there has been a lack of epidemiological studies of human exposure to hexavalent Cr by drinking water or ingestion, and it has been suggested that humans can perhaps tolerate hexavalent Cr at higher levels than the current drinking water standard of 50 ppb. This review highlights the most recent data on the induction of skin tumors in mice by chronic drinking-water exposure to hexavalent chromium in combination with solar ultraviolet light. This experimental system represents an important new animal model for chromate-induced cancers by ingestion of drinking water, and it suggests by extrapolation that chromate can likely be considered a human carcinogen by ingestion as well. The potential use of this animal model for future risk assessment is discussed.
Following the seminal work of Ingvar (1985. "Memory for the future": An essay on the temporal organization of conscious awareness. Human Neurobiology, 4, 127-136), Suddendorf (1994. The discovery of ...the fourth dimension: Mental time travel and human evolution. Master's thesis. University of Waikato, Hamilton, New Zealand), and Tulving (1985. Memory and consciousness. Canadian Psychology/PsychologieCanadienne, 26, 1-12), exploration of the ability to anticipate and prepare for future contingencies that cannot be known with certainty has grown into a thriving research enterprise. A fundamental tenet of this line of inquiry is that future-oriented mental time travel, in most of its presentations, is underwritten by a property or an extension of episodic recollection. However, a careful conceptual analysis of exactly how episodic memory functions in this capacity has yet to be undertaken. In this paper I conduct such an analysis. Based on conceptual, phenomenological, and empirical considerations, I conclude that the autonoetic component of episodic memory, not episodic memory per se, is the causally determinative factor enabling an individual to project him or herself into a personal future.
Background. Anal cancer is one of the most common cancers affecting individuals infected with human immunodeficiency virus (HIV), although few have evaluated rates separately for men who have sex ...with men (MSM), other men, and women. There are also conflicting data regarding calendar trends. Methods. In a study involving 13 cohorts from North America with follow-up between 1996 and 2007, we compared anal cancer incidence rates among 34 189 HIV-infected (55% MSM, 19% other men, 26% women) and 114 260 HIV-uninfected individuals (90% men). Results. Among men, the unadjusted anal cancer incidence rates per 100 000 person-years were 131 for HIV-infected MSM, 46 for other HIV-infected men, and 2 for HIV-uninfected men, corresponding to demographically adjusted rate ratios (RRs) of 80.3 (95% confidence interval CI, 42.7—151.1) for HIV-infected MSM and 26.7 (95% CI, 11.5—61.7) for other HIV-infected men compared with HIV-uninfected men. HIV-infected women had an anal cancer rate of 30/100 000 person-years, and no cases were observed for HIV-uninfected women. In a multivariable Poisson regression model, among HIV-infected individuals, the risk was higher for MSM compared with other men (RR, 3.3; 95% CI, 1.8—6.0), but no difference was observed comparing women with other men (RR, 1.0; 95% CI, 0.5—2.2). In comparison with the period 2000—2003, HIV-infected individuals had an adjusted RR of 0.5 (95% CI, .3—.9) in 1996—1999 and 0.9 (95% CI, .6—1.2) in 2004—2007. Conclusions. Anal cancer rates were substantially higher for HIV-infected MSM, other men, and women compared with HIV-uninfected individuals, suggesting a need for universal prevention efforts. Rates increased after the early antiretroviral therapy era and then plateaued.
Background Mutations in STK11 (STK11m) and frequently co-occurring KRAS mutations (KRASm/STK11m) are associated with poor survival in metastatic NSCLC (mNSCLC) immuno-oncology trials. There are ...limited data regarding the prognostic significance of these mutations in a real-world setting. Methods This retrospective cohort study analyzed de-identified electronic medical records from the Flatiron Clinico-Genomic database to identify patients with mNSCLC who had initiated first-line immunotherapy (IO; alone or in combination) or chemotherapy under routine care between January 1, 2013 and June 30, 2017. The primary objectives were to assess the prevalence of STK11m and KRASm/STK11m and to determine associations of these mutations with overall and progression-free survival (OS, PFS). Results Of 2407 patients with mNSCLC, STK11m and KRASm/STK11m were present in 13.6% and 6.5% of patients, respectively. Worse OS outcomes were observed in patients with STK11m versus STK11wt mNSCLC receiving IO (first-line, HR 95% CI, 1.4 0.9–2.3; p = 0.1; second-line subset of first-line cohort, HR, 1.6 1.3–2.0; p = 0.0002) or chemotherapy (first-line, HR, 1.4 1.2–1.6; p < 0.0001); PFS outcomes showed similar trends. KRASm/STK11m double mutations were associated with worse OS and PFS outcomes versus KRASwt/STK11wt with IO and chemotherapy, similar to the single mutation (STK11m vs STK11wt) findings. Conclusions This large observational genomic study among patients receiving routine care highlights the negative prognostic impact of STK11m in patients with mNSCLC treated with IO or chemotherapy. These results complement previous clinical trial data and provide further evidence in the real world of a patient population that would benefit from new treatment options.
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