Processing complex sounds passing through the rostral brainstem : The new early filter model

The rostral brainstem receives both “bottom-up” input from the ascending auditory system and “top-down” descending corticofugal connections. Speech information passing through the inferior colliculus of elderly listeners reflects the periodicity envelope of a speech syllable. This information arguably also reflects a composite of temporal-fine-structure (TFS) information from the higher frequency vowel harmonics of that repeated syllable. The amplitude of those higher frequency harmonics, bearing high frequency TFS information, correlates positively with the word recognition ability of elderly listeners under reverberatory conditions. Also relevant is that working memory capacity, which is subject to age-related decline, constrains the processing of sounds at the level of the brainstem. Turning to the effects of a visually presented sensory or memory load on auditory processes, there is a load-dependent reduction of that processing, as manifest in the auditory brainstem responses evoked by to-be-ignored clicks. Wave V decreases in amplitude with increases in the visually presented memory load. A visually presented sensory load also produces a load-dependent reduction of a slightly different sort: The sensory load of visually presented information limits the disruptive effects of background sound upon working memory performance. A new early filter model is thus advanced whereby systems within the frontal lobe (affected by sensory or memory load) cholinergically influence top-down corticofugal connections. Those corticofugal connections constrain the processing of complex sounds such as speech at the level of the brainstem. Selective attention thereby limits the distracting effects of background sound entering the higher auditory system via the inferior colliculus. Processing TFS in the brainstem relates to perception of speech under adverse conditions. Attentional selectivity is crucial when the signal heard is degraded or masked: e.g., speech in noise, speech in reverberatory environments. The assumptions of a new early filter model are consistent with these findings: A subcortical early filter, with a predictive selectivity based on acoustical (linguistic) context and foreknowledge, is under cholinergic top-down control. A limited prefrontal capacity limitation constrains this top-down control as is guided by the cholinergic processing of contextual information in working memory.Peer reviewe

Introducing the Edges Paradigm: A P300 Brain-Computer Interface for spelling written words.

P300-based brain–computer interface spellers employ the P300 component, which is derived from scalp measured electroencephalogram during the brain’s electrical response to a flash denoting an attended target character. The most popular P300 speller, the row–column paradigm (RCP), displays characters in a matrix within which rows and columns of characters are flashed eliciting P300 responses when the illuminated row or column contains the attended target character. Despite being a longstanding successful approach, this RCP faces several challenges, including the adjacency and crowding problems. A new P300 speller is introduced—the edges paradigm (EP). Distinct from existing P300 spellers, the EP presents a square adjacent to each column or row in the outer boundary of the matrix. By replacing each flash of a row or column with that square, this EP exhibited attenuated influences of crowding and adjacency—problems known to perturb the RCP. In the copy-spelling mode, 14 neurologically normal participants demonstrated an improved accuracy of 93.3 +\- 2.0% for the EP relative to 81.7 +\- 2.8% for the RCP, alongside a faster communication rate. Subjective ratings also indicated that the EP caused significantly less fatigue, while increasing alertness and comfort.Peer reviewe

Ophthalmic manifestations of Cryptococcus gattii species complex: a case series and review of the literature

AIM: To report 4 cases of Cryptococcus gattii (C. gattii) species complex infection with diverse ophthalmic manifestations, and to review the literature to examine pathobiology of disease, classical ophthalmic presentations and outcomes, and treatment modalities for this emerging pathogen. METHODS: Cases of C. gattii meningoencephalitis with ophthalmic manifestations were identified via chart review at two institutions in Australia and one institution in the mid-west region of the United States and are reported as a case series. Additionally, a MEDLINE literature review was conducted to identify all reported cases of C. gattii with ophthalmic manifestations from 1990-2020. Cases were reviewed and tabulated, together with our series of patients, in this report. RESULTS: Four cases of C. gattii with ophthalmic manifestations are presented; three from Australia and one from the USA. A literature review identified a total of 331 cases of C. gattii with visual sequelae. The majority of cases occurred in immunocompetent individuals. Blurred vision and diplopia were the most common presenting symptoms, with papilloedema the most common sign, reported in 10%-50% of cases. Visual loss was reported in 10%-53% of cases, as compared to rates of visual loss of 1%-9% in C. neoformans infection. Elevated intracranial pressure, cerebrospinal fluid (CSF) fungal burden, and abnormal neurological exam at presentation correlated with poor visual outcomes. The mainstays of treatment are anti-fungal agents and aggressive management of intracranial hypertension with serial lumbar punctures. CSF diversion procedures should be considered for refractory cases. Acetazolamide and mannitol are associated with high complication rates, and adjuvant corticosteroids have demonstrated higher mortality rates; these treatments should be avoided. CONCLUSION: Permanent visual loss represents a devastating yet potentially preventable sequelae of C. gattii infection. Intracranial hypertension needs to be recognised early and aggressively managed. Referral to an ophthalmologist/neuro-ophthalmologist in all cases of cryptococcal infection independent of visual symptoms at time of diagnosis is recommended

Safety and pharmacokinetics of MM-302, a HER2-targeted antibody–liposomal doxorubicin conjugate, in patients with advanced HER2-positive breast cancer: A phase 1 dose-escalation study

BackgroundThis phase 1 dose-escalation trial studied MM-302, a novel HER2-targeted PEGylated antibody-liposomal doxorubicin conjugate, in HER2-positive locally advanced/metastatic breast cancer.MethodsPatients were enrolled in four cohorts: MM-302 monotherapy (8, 16, 30, 40, and 50 mg/m2 every 4 weeks [q4w]); MM-302 (30 or 40 mg/m2 q4w) plus trastuzumab (4 mg/kg q2w); MM-302 (30 mg/m2) plus trastuzumab (6 mg/kg) q3w; MM-302 (30 mg/m2) plus trastuzumab (6 mg/kg) and cyclophosphamide (450 mg/m2) q3w.ResultsSixty-nine patients were treated. The most common adverse events (AEs) were fatigue and nausea. Grade 3/4 AEs of special interest included neutropenia, fatigue, mucosal inflammation, anemia, thrombocytopenia, febrile neutropenia, and palmar-plantar erythrodysesthesia. The MTD was not reached. With MM-302 ≥ 30 mg/m2, overall response rate (ORR) was 13% and median progression-free survival (mPFS) 7.4 months (95% CI: 3·5-10·9) in all arms. In 25 anthracycline-naïve patients, ORR was 28·0% and mPFS 10·9 months (95% CI: 1·8-15·3). Imaging with 64Cu-labeled MM-302 visualized tumor-drug penetrance in tumors throughout the body, including the brain.ConclusionMM-302 monotherapy, in combination with trastuzumab, or trastuzumab plus cyclophosphamide, was well tolerated and showed promising efficacy. The selected phase 2 MM-302 dose was 30 mg/m2 plus 6 mg/kg trastuzumab q3w

Successful resuscitation of an elderly man with deep accidental hypothermia using portable extracorporeal circulation in the emergency department: a case report

<p>Abstract</p> <p>Introduction</p> <p>Deep accidental hypothermia (body temperature below 28°C) is rare and has a high mortality rate. Successful resuscitation usually occurs in the young, but a prompt intervention using a portable extracorporeal cardiopulmonary circulation device can also provide a good outcome for older persons.</p> <p>Case presentation</p> <p>We report the successful resuscitation of an 82-year-old male from deep accidental hypothermia using portable extracorporeal circulation in the emergency department.</p> <p>Conclusion</p> <p>This successful resuscitation of an 82-year-old patient demonstrates that a prompt intervention by a medical team that trains together, using a mobile cardiopulmonary bypass device via a percutaneous approach, can potentially provide good outcomes for all victims of deep accidental hypothermia, both in the operating suites and the emergency department.</p

Outcomes of treatment of synovial sarcoma

Introduction Synovial sarcoma accounts for 5% to 10% of malignant soft-tissue tumours. It occurs more commonly in males. Treatment options include surgery, radiotherapy and chemotherapy with the latter two being used in either an induction or adjuvant fashion. We review the 15-year experience of management of synovial sarcoma patients (2000-2015) referred to the East Midlands Sarcoma Service to allow for 5-year follow-up Methods Patients were identified from histopathology data held at Leicester and Nottingham. Data were stored in a secure Microsoft Excel spreadsheet. Results 97 patients (49 male) were identified, mean age 42 years (range 8 – 83 years); data were incomplete on 3 patients. 51 (53%) arose in the lower limb. Size at presentation was 38 10cm. 50 patients developed metastatic disease (7 presented with metastases) and 15 patients local recurrence over the course of treatment. The majority of patients were treated with surgery as the primary treatment modality although larger tumours received radiotherapy either as induction or adjuvant. Chemotherapy as a curative treatment was only used for small numbers of patients, although was more commonly used palliatively. Discussion Multi-modality treatment for synovial sarcomas is increasingly commonly used with a view to improving oncologic outcomes. In this unselected series of synovial sarcomas over 50% of patients relapse from the disease and appropriate targeting of those at high risk of relapse may offer a therapeutic advantage. Further work on the dataset continues to identify particular risk factors for relapse

BK Lyncis: The Oldest Old Nova?... And a Bellwether for Cataclysmic-Variable Evolution

We summarize the results of a 20-year campaign to study the light curves of BK Lyncis, a nova-like star strangely located below the 2-3 hour orbital period gap in the family of cataclysmic variables. Two apparent "superhumps" dominate the nightly light curves - with periods 4.6% longer, and 3.0% shorter, than P_orb. The first appears to be associated with the star's brighter states (V~14), while the second appears to be present throughout and becomes very dominant in the low state (V~15.7). Starting in the year 2005, the star's light curve became indistinguishable from that of a dwarf nova - in particular, that of the ER UMa subclass. Reviewing all the star's oddities, we speculate: (a) BK Lyn is the remnant of the probable nova on 30 December 101, and (b) it has been fading ever since, but has taken ~2000 years for the accretion rate to drop sufficiently to permit dwarf-nova eruptions. If such behavior is common, it can explain other puzzles of CV evolution. One: why the ER UMa class even exists (because all members can be remnants of recent novae). Two: why ER UMa stars and short-period novalikes are rare (because their lifetimes, which are essentially cooling times, are short). Three: why short-period novae all decline to luminosity states far above their true quiescence (because they're just getting started in their postnova cooling). Four: why the orbital periods, accretion rates, and white-dwarf temperatures of short-period CVs are somewhat too large to arise purely from the effects of gravitational radiation (because the unexpectedly long interval of enhanced postnova brightness boosts the mean mass-transfer rate). These are substantial rewards in return for one investment of hypothesis: that the second parameter in CV evolution, besides P_orb, is time since the last classical-nova eruption.Comment: PDF, 46 pages, 4 tables, 10 figures; in preparation; more info at http://cbastro.org

Securing Information Technology in Healthcare

Information technology (IT) has great potential to improve healthcare quality while also improving efficiency, and thus has been a major focus of recent healthcare reform efforts. However, developing, deploying and using IT that is both secure and genuinely effective in the complex clinical, organizational and economic environment of healthcare is a significant challenge. Further, it is imperative that we better understand the privacy concerns of patients and providers, as well as the ability of current technologies, policies, and laws to adequately protect privacy. The Securing Information Technology in Healthcare (SITH) workshops were created to provide a forum to discuss security and privacy for experts from a broad range of perspectives, from officers at large healthcare companies, startups and nonprofits, to physicians, researchers and policy makers

Shallow radar (SHARAD) sounding observations of the Medusae Fossae Formation, Mars

The SHARAD (shallow radar) sounding radar on the Mars Reconnaissance Orbiter detects subsurface reflections in the eastern and western parts of the Medusae Fossae Formation (MFF). The radar waves penetrate up to 580 m of the MFF and detect clear subsurface interfaces in two locations: west MFF between 150 and 155◦ E and east MFF between 209 and 213◦ E. Analysis of SHARAD radargrams suggests that the real part of the permittivity is ∼3.0, which falls within the range of permittivity values inferred from MARSIS data for thicker parts of the MFF. The SHARAD data cannot uniquely determine the composition of the MFF material, but the low permittivity implies that the upper few hundred meters of the MFF material has a high porosity. One possibility is that the MFF is comprised of low-density welded or interlocked pyroclastic deposits that are capable of sustaining the steep-sided yardangs and ridges seen in imagery. The SHARAD surface echo power across the MFF is low relative to typical martian plains, and completely disappears in parts of the east MFF that correspond to the radar-dark Stealth region. These areas are extremely rough at centimeter to meter scales, and the lack of echo power is most likely due to a combination of surface roughness and a low near-surface permittivity that reduces the echo strength from any locally flat regions. There is also no radar evidence for internal layering in any of the SHARAD data for the MFF, despite the fact that tens-of-meters scale layering is apparent in infrared and visible wavelength images of nearby areas. These interfaces may not be detected in SHARAD data if their permittivity contrasts are low, or if the layers are discontinuous. The lack of closely spaced internal radar reflectors suggests that the MFF is not an equatorial analog to the current martian polar deposits, which show clear evidence of multiple internal layers in SHARAD dat