Convergent and invariant object representations for sight,sound, and touch

We continuously perceive objects in the world through multiple sensory channels. In this study, we investigated the convergence of information from different sensory streams within the cerebral cortex. We presented volunteers with three common objects via three different modalities—sight, sound, and touch—and used multivariate pattern analysis of functional magnetic resonance imaging data to map the cortical regions containing information about the identity of the objects. We could reliably predict which of the three stimuli a subject had seen, heard, or touched from the pattern of neural activity in the corresponding early sensory cortices. Intramodal classification was also successful in large portions of the cerebral cortex beyond the primary areas, with multiple regions showing convergence of information from two or all three modalities. Using crossmodal classification, we also searched for brain regions that would represent objects in a similar fashion across different modalities of presentation. We trained a classifier to distinguish objects presented in one modality and then tested it on the same objects presented in a different modality. We detected audiovisual invariance in the right temporo‐occipital junction, audiotactile invariance in the left postcentral gyrus and parietal operculum, and visuotactile invariance in the right postcentral and supramarginal gyri. Our maps of multisensory convergence and crossmodal generalization reveal the underlying organization of the association cortices, and may be related to the neural basis for mental concepts. Hum Brain Mapp 36:3629–3640, 2015. © 2015 Wiley Periodicals, Inc.     

Evidence for involvement of central noradrenergic neurons in the cardiovascular depression induced by morphine in the rat

Summary Morphine caused in the anaesthetized rat reduction in brain noradrenaline (NA) turnover, hypotension and bradycardia, similarly to the antihypertensive,-adrenergic agonist, clonidine. All effects of morphine were antagonized by naloxone, as well as the-receptor antagonist, yohimbine. In contrast, naloxone did not affect the circulatory depression and reduction in brain NA utilization by clonidine, which both previously have been found to be antagonized by yohimbine. In contrast to clonidine, morphine even in high doses did not facilitate the flexor reflex activity of acutely spinalized rats. Pretreatment with protriptylin largely attenuated the circulatory depressive effects of morphine, as it has previously been found to block the corresponding effects of clonidine. Thus, the morphine-induced cardiovascular depressive effects are primarily elicited by activation of opiate receptors. However, the inhibition of brain NA neurotransmission by morphine appears critically involved in the mediation of the circulatory depression.     

Prostaglandin E2 release evoked by intrathecal dynorphin is dependent on spinal p38 mitogen activated protein kinase

Spinal dynorphin has been hypothesized to play a pivotal role in spinal sensitization. Although the mechanism of this action is not clear, several lines of evidence suggest that spinal dynorphin-induced hyperalgesia is mediated through an increase in spinal cyclooxygenase products via an enhanced N-methyl-D-aspartate (NMDA) receptor function. Spinal NMDA-evoked prostaglandin release and nociception has been linked to the activation of p38 mitogen activated protein kinase (p38). In the present work, we show that intrathecal delivery of an N-truncated fragment of dynorphin A, dynorphin A 2-17 (dyn2-17), which has no activity at opioid receptors, induced a 8-10-fold increase in phosphorylation of p38 in the spinal cord. The increase in phosphorylated p38 was detected in laminae I-IV of the dorsal horn. Moreover, confocal microscopy showed that the activation of p38 occurred in microglia, but not in neurons or astrocytes. In awake rats, prepared with chronically placed intrathecal loop dialysis catheters, the concentration of prostaglandin E2 in lumbar cerebrospinal fluid was increased 5-fold by intrathecal administration of dyn2-17. Injection of SD-282, a selective p38 inhibitor, but not PD98059, an ERK1/2 inhibitor, attenuated the prostaglanin E2 release. These data, taken together, support the hypothesis that dynorphin, independent of effects mediated by opioid receptors, has properties that can induce spinal sensitization and indicates that dyn2-17 effects may be mediated through activation of the p38 pathway. These studies provide an important downstream linkage where by dynorphin may act through a non-neuronal link to induce a facilitation of spinal nociceptive processing.     

Frameless stereotactic radiosurgery for recurrent head and neck carcinoma

The aim of this study was to assess the feasibility and toxicity of stereotactic radiosurgery (CK-SRS) using the CyberKnife Frameless Radiosurgery System (Accuray Inc., Sunnyvale, CA) in the management of recurrent squamous cell carcinoma of the head and neck region (SCCHN). Between November 2001 and February 2004, 22 patients with recurrent, previously irradiated SCCHN were treated with CK-SRS. The following endpoints were assessed post-CK-SRS: local control (LC), cause-specific survival (CSS), overall survival (OS), symptom relief, and acute and late toxicity. Kaplan-Meier survival analyses were used to estimate the LC, CSS, and OS rates. Clinical symptoms were graded as "improved," "stable," or "progressed" after CK-SRS. Acute and late toxicity were graded according to the National Cancer Institute Common Toxicity Criteria (CTC) scale, version 2.0. Seventeen patients were followed until their death. The median follow-up in the remaining five patients was 19 months (range 11-40 months). The median survival time for the entire cohort was 12 months from the time of CK-SRS. The 2-year LC, CSS, and OS rates were 26%, 26%, and 22%, respectively. After CK-SRS, symptoms were improved or stable in all but one patient who reported increasing pain. The treatment was well tolerated, with one case each of Grade 2 and 3 mucositis. There were no acute Grade 4 or 5 CTC toxicities. There were no late toxicities in this cohort. Frameless stereotactic radiosurgery for recurrent SCCHN is feasible and safe in the setting of high doses of prior irradiation. The majority of patients experienced palliation of disease without excess toxicity.     

Acrometastasis to the foot: an unusual presentation of transitional cell carcinoma of the bladder

Metastases from bladder cancer to the bones of the hands or feet are rare and usually present after the diagnosis of the primary lesion has been made. This case report describes a 76-year-old man presenting with initial signs of infection of the right foot. Subsequent bone scan revealed multiple bony metastases and hydronephrosis raising the possibility of a primary bladder tumour that was later confirmed by urine cytology and fine needle aspiration of the foot.     

Dose-dependent effects of budesonide aqueous nasal spray on symptoms in a daily nasal allergen challenge model.

BACKGROUND: It has been difficult to demonstrate dose-dependent clinical effects of anti-allergic glucocorticosteroid drugs in allergic rhinitis. OBJECTIVE: To determine dose-dependent effects on rhinitis symptoms of clinical doses of the glucocorticosteroid budesonide in a standardized daily allergen challenge model. METHODS: Twenty-five patients with seasonal allergic rhinitis were examined outside the pollen season. The highest 256 microg once daily and lowest 64 microg once daily clinically recommended doses of budesonide aqueous nasal spray and placebo were given in a double-blind, placebo-controlled, randomized, and crossover design with 4 weeks' washout between treatments. After 1 week's treatment, the patients received individually titrated nasal allergen challenges once every morning for 8 days while treatment continued. Nasal symptoms were scored in diary cards. Nasal symptoms from the 6th to the 8th challenge days were used in the analysis. RESULTS: The provocation model produced clinically relevant, and around the clock well tolerable rhinitis symptoms, suggesting that after several days of repeated allergen challenges, a season-like, transient allergic disease condition had been established. Both 64 microg and 256 microg of budesonide aqueous nasal spray reduced nasal symptoms. Budesonide 64 microg reduced total nasal symptoms scores from 5.19 +/- 0.5 to 4.23 +/- 0.53 (P < .05), and budesonide 256 microg reduced total nasal symptoms scores to 3.41 +/- 0.51 (P < .001). A significant difference in nasal symptoms after challenge between budesonide aqueous nasal spray 64 microg and 256 microg (P = .03), indicated a dose-dependent effect. CONCLUSIONS: A dose-dependent, symptom-reducing effect of once-daily treatment with topical aqueous nasal sprays of budesonide for two weeks was demonstrated, suggesting that this model is relevant for assessments of dose-dependent effects of anti-inflammatory drugs.     

Mask wearing in community settings reduces SARS-CoV-2 transmission

The effectiveness of mask wearing at controlling severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) transmission has been unclear. While masks are known to substantially reduce disease transmission in healthcare settings [D. K. Chu et al., Lancet 395, 1973–1987 (2020); J. Howard et al., Proc. Natl. Acad. Sci. U.S.A. 118, e2014564118 (2021); Y. Cheng et al., Science eabg6296 (2021)], studies in community settings report inconsistent results [H. M. Ollila et al., medRxiv (2020); J. Brainard et al., Eurosurveillance 25, 2000725 (2020); T. Jefferson et al., Cochrane Database Syst. Rev. 11, {"type":"entrez-nucleotide","attrs":{"text":"CD006207","term_id":"30322945","term_text":"CD006207"}}CD006207 (2020)]. Most such studies focus on how masks impact transmission, by analyzing how effective government mask mandates are. However, we find that widespread voluntary mask wearing, and other data limitations, make mandate effectiveness a poor proxy for mask-wearing effectiveness. We directly analyze the effect of mask wearing on SARS-CoV-2 transmission, drawing on several datasets covering 92 regions on six continents, including the largest survey of wearing behavior (n= 20 million) [F. Kreuter et al., https://gisumd.github.io/COVID-19-API-Documentation (2020)]. Using a Bayesian hierarchical model, we estimate the effect of mask wearing on transmission, by linking reported wearing levels to reported cases in each region, while adjusting for mobility and nonpharmaceutical interventions (NPIs), such as bans on large gatherings. Our estimates imply that the mean observed level of mask wearing corresponds to a 19% decrease in the reproduction number R. We also assess the robustness of our results in 60 tests spanning 20 sensitivity analyses. In light of these results, policy makers can effectively reduce transmission by intervening to increase mask wearing.

Face masks are one of the most prominent interventions against COVID-19, with very high uptake in most countries (1). However, global mask wearing fell substantially in 2021, even in countries with low vaccination rates (Fig. 1). Given ongoing epidemics, establishing the effectiveness of mask wearing in community settings is critical. The following sections review past work on the effectiveness of mask wearing in different settings and at different scales.Open in a separate windowFig. 1.Reported mask wearing in countries with <40% of population fully vaccinated, as of 1 October 2021 [wearing from the UMD/Facebook survey (1); vaccinations from ref. 2]. The y axis is the proportion who reported that, over the last week, they wore masks most or all of the time in public spaces.In the context of healthcare, N95 masks (as defined by ref. 3) work well when worn properly by trained users—reducing transmission of coronaviruses including severe acute respiratory coronavirus syndrome 2 (SARS-CoV-2) by at least half (4, 5). Cheng et al. (6) find that ideal surgical masking (7, 8) of a noninfected person corresponds to a 65 to 75% reduction in their risk of COVID-19.However, the effect of mask wearing in small-scale community settings is more difficult to detect.In particular, four meta-analyses have summarized studies on respiratory infections, conducted in community settings (4, 9–11). They estimate mean decreases in infection risk between 4% and 15% for surgical masks, but with large uncertainty: Individual results ranged from a 7% increase in infection risk to a 61% decrease in infection risk. In addition, few of these studies are randomized controlled trials (RCTs), and those that are RCTs have considerable issues: Bungaard et al. (12) found a small, nonsignificant reduction in infection risk. Abaluck et al. (13), found a significant, 8.6% decrease in symptomatic seropositivity linked to mask wearing. However, limitations of the study included a requirement for unblinded participants to self-report symptoms before testing, use of an antibody test with a very low 5 d sensitivity, and unclear generalization from the specific context (rural villages in Bangladesh).We focus on the effects of mask wearing or mandates (i.e., legal requirements to wear a mask) on transmission in large connected populations. To study mask impacts on transmission, many studies use the timing of mask mandates as a proxy for sharp changes in the level of mask wearing. Some such studies have inferred limited or inconclusive effects in cross-country analyses (14) and within-country studies (15), while others find cross-country evidence that mask mandates and recommendations lead to decreased transmission and mortality (16, 17).Other analyses provide evidence for reduced case growth following subnational mandates within countries such as the United States (18–20) and Germany (21). A potential explanation for the inconsistency and uncertainty of these results is that data on national mandate timing may be poorly suited for analyzing the effects of mask wearing on transmission.Epidemiological studies often use government mask mandates as a proxy for mask wearing. However, the existing literature on the relationship between mandates and actual levels of mask wearing has shown surprisingly weak effects. For example, studying US states, ref. 22 failed to find a statistically significant relationship between mandates and subsequent wearing, while other studies found postmandate increases in wearing of just 13% (23) and 23% (24). Betsch et al. (25) find a ∼40% increase in wearing after local mandates in Germany, but no other study finds a comparably large increase. Given that the link between mandates and wearing is surprisingly weak, it is likely that the link between mandates and transmission is difficult to detect. Three additional factors lead us to suspect that a link between mandates and transmission would be difficult to detect. First, introducing a mandate is a coarse, one-off event that necessarily loses signal by not tracking day-to-day changes in mask wearing. We also have fewer data on mandates: Less than half of the regions we study enforced any mandate during the study period. Second, past studies treat mandates as a binary on/off intervention that is fully implemented at a single point in time. However, modeling the effect of mandates as an instantaneous change in the reproduction number or mortality fails to capture changes in wearing behavior following the announcement of a mandate but before its enforcement (21). Nor does it account for gradual change in behavior after the implementation of a mandate. Finally, the circumstances of mandate policies are highly heterogeneous, both in terms of the preexisting level of voluntary wearing at the time of implementation and in terms of how exactly they are defined, enforced, and complied with. Consequently, averaging the international effect of mandates based on coarse data is unlikely to provide a useful summary of heterogeneous mandate effects. Importantly, these arguments point to the link between mandates and transmission being difficult to detect, not that it is absent.Because of these difficulties in studying the effect of mandates, we instead focus on estimating the effect of mask wearing on transmission, using a large (n = 19.97 million) global survey of self-reported mask wearing (1). Two other studies estimate mask effectiveness from self-reports: In their study of 24 countries, Aravindakshan et al. (26) use YouGov wearing data to infer an overall 3.9 to 10% relative decrease in case growth rate from whole population mask wearing. Rader et al. (22) study US states using a novel SurveyMonkey wearing dataset to infer a ∼10% decrease in transmission between the lowest and highest empirical quartiles of wearing (a 50 to 75% increase in wearing). Rader et al. use data limited to 12 US states during June–July 2020. Our data are richer: We study 56 countries on six continents, and our inferential analyses span May–September 2020.Our analysis goes further than past work in the quality of wearing data—100 times the sample size, with random sampling and poststratification—the geographical scope, the use of a semimechanistic infection model, the incorporation of uncertainty into epidemiological parameters, and the robustness of our results (59 sensitivity tests). See

Preoperative transcatheter closure of congenital muscular ventricular septal defects

BACKGROUND. Surgical repair of muscular ventricular septal defects, particularly those associated with complex heart lesions carries a higher risk of reoperation and death than the repair of membranous defects. Closing a muscular defect through an incision in the systemic ventricle may cause late ventricular dysfunction. In a collaborative approach to this problem, we undertook preoperative transcatheter closure of muscular ventricular septal defects remote from the atrioventricular and semilunar valves, followed by the surgical repair of associated conditions. METHODS. In 12 patients selected jointly by a cardiologist and a cardiac surgeon, we attempted preoperative transcatheter umbrella closure of 21 defects. Half the patients had associated complex heart lesions; the others had had pulmonary-artery banding to reduce the amount of left-to-right shunting. Half had severe ventricular septal deficiency. RESULTS. All 21 defects were successfully closed without major complications. Subsequent cardiac surgery for associated conditions in 11 of the 12 patients resulted in a mean pulmonary-to-systemic flow ratio of 1.1, indicating minimal residual left-to-right shunting; 1 patient awaited surgical repair. No deaths, reoperations, or late complications have occurred after a follow-up of 7 to 20 months. CONCLUSIONS. A collaborative approach using transcatheter closure followed by the surgical repair of associated cardiac lesions may decrease rates of operative mortality, reoperation, and left ventricular dysfunction in patients with muscular ventricular septal defects.     

The nine stages of skin‐to‐skin: practical guidelines and insights from four countries

Incorporating systematic evidence with clinical expertise is a key element in the quest to improve quality of care and patient outcomes. The evidence supporting skin‐to‐skin contact in the first hour after birth is robust and includes significantly improved outcomes for both mother and infant. This paper compares available iterative data about newborn behaviour in the first hour after birth to further describe the observable behaviour pattern and to provide clinical insight for further research. Although the evidence for positive outcomes through skin‐to‐skin contact are robust, there is a dearth of research specifically focused on clinical practice. The methodology considers the four available data sets that used Widström's 9 stages, which consists of studies from Japan, Sweden, Italy and the United States, examining the parameters of each stage across settings from around the world. This research provides an expanded understanding of the timing of the newborn's progression through Widström's 9 observable stages. We found that newborns in all four data sets began with a birth cry and continued through the remaining stages of relaxation, awakening, activity, rest, crawling, familiarization, suckling and sleeping during the first hours after birth and consolidated the data into a Sign of the Stages chart to assist in further research. The evidence supports making a safe space and time for this important newborn behaviour. Clinical practices should encourage and protect this sensitive period.