Reliability and Confidence of Dynamic Imaging Grade of Swallowing Toxicity (DIGEST) Rating Among Research and Clinical Speech Pathologists Before and After Implementation of a Training Manual: A Multi-site Study.

DIGEST is a validated, open-source method to grade the severity of pharyngeal dysphagia from the modified barium swallow (MBS) study. Dissemination and implementation of DIGEST is rising, making it critical to understand reliability and facilitators of accurate implementation among users. The aim was to assess reliability of the tool among speech-language pathology (SLP) raters practicing at multiple sites before and after review of a DIGEST training manual and evaluate confidence of DIGEST use pre-and post-training. Thirty-two SLPs from 5 sites participated in a blinded longitudinal DIGEST rating study. Raters were provided a standardized training set of MBS (n = 19). Initial SLP ratings (round 1, R1) were followed by a 2-4 week break before raters rated a re-keyed MBS set (round 2, R2). A minimum 4-8 week wash-out period then preceded self-study of the DIGEST training manual which was followed by a final rating (round 3, R3) and a post-manual survey afterwards. Baseline reliability (R1) of overall DIGEST was on average k = 0.70, reflecting agreement in the substantial range. Seventy-five percent of raters (24/32) demonstrated reliability ≥ 0.61 in the substantial to almost perfect range prior to training. Inter-rater reliability significantly improved from R1 to R3 after review of the DIGEST manual, with the largest change in DIGEST-Efficiency (mean change: DIGEST k = .04, p = .009, DIGEST-Safety k = .07, p = 0.03, and DIGEST-Efficiency k = .14, p = 0.009). Although DIGEST reliability at baseline was adequate in the majority of raters, self-study of the DIGEST training manual significantly improved inter-rater reliability and rater confidence using the DIGEST method, particularly when assigning DIGEST-Efficiency grade. These early data show promise that provider training may be useful to aid in fidelity of DIGEST implementation among SLP clinical users with varying DIGEST experience.

A report of Bilharziella polonica cercariae in Knowsley Safari, Prescot, United Kingdom, with notes on other trematodes implicated in human cercarial dermatitis.

As part of surveillance of snail-borne trematodiasis in Knowsley Safari (KS), Prescot, United Kingdom, a collection was made in July 2021 of various planorbid (n = 173) and lymnaeid (n = 218) snails. These were taken from 15 purposely selected freshwater habitats. In the laboratory emergent trematode cercariae, often from single snails, were identified by morphology with a sub-set, of those most accessible, later characterized by cytochrome oxidase subunit 1 (cox1) DNA barcoding. Two schistosomatid cercariae were of special note in the context of human cercarial dermatitis (HCD), Bilharziella polonica emergent from Planorbarius corneus and Trichobilharzia spp. emergent from Ampullacaena balthica. The former schistosomatid was last reported in the United Kingdom over 50 years ago. From cox1 analyses, the latter likely consisted of two taxa, Trichobilharzia anseri, a first report in the United Kingdom, and a hitherto unnamed genetic lineage having some affiliation with Trichobilharzia longicauda. The chronobiology of emergent cercariae from P. corneus was assessed, with the vertical swimming rate of B. polonica measured. We provide a brief risk appraisal of HCD for public activities typically undertaken within KS educational and recreational programmes.

Prospects for the elimination of schistosomiasis and soil-transmitted helminthiasis: exploring disease trends through time at the Barombi crater lakes, South-West Cameroon.

In Cameroon, there is a national programme engaged in the control of schistosomiasis and soil-transmitted helminthiasis. In certain locations, the programme is transitioning from morbidity control towards local interruption of parasite transmission. The volcanic crater lake villages of Barombi Mbo and Barombi Kotto are well-known transmission foci and are excellent context-specific locations to assess appropriate disease control interventions. Most recently they have served as exemplars of expanded access to deworming medications and increased environmental surveillance. In this paper, we review infection dynamics through time, beginning with data from 1953, and comment on the short- and long-term success of disease control. We show how intensification of local control is needed to push towards elimination and that further environmental surveillance, with targeted snail control, is needed to consolidate gains in preventive chemotherapy as well as empower local communities to take ownership of interventions.

First Demonstration of Electrostatic Damping of Parametric Instability at Advanced LIGO.

Interferometric gravitational wave detectors operate with high optical power in their arms in order to achieve high shot-noise limited strain sensitivity. A significant limitation to increasing the optical power is the phenomenon of three-mode parametric instabilities, in which the laser field in the arm cavities is scattered into higher-order optical modes by acoustic modes of the cavity mirrors. The optical modes can further drive the acoustic modes via radiation pressure, potentially producing an exponential buildup. One proposed technique to stabilize parametric instability is active damping of acoustic modes. We report here the first demonstration of damping a parametrically unstable mode using active feedback forces on the cavity mirror. A 15 538 Hz mode that grew exponentially with a time constant of 182 sec was damped using electrostatic actuation, with a resulting decay time constant of 23 sec. An average control force of 0.03 nN was required to maintain the acoustic mode at its minimum amplitude.

The impact of critical event checklists on medical management and teamwork during simulated crises in a surgical daycare facility.

Although the incidence of major adverse events in surgical daycare centres is low, these critical events may not be managed optimally due to the absence of resources that exist in larger hospitals. We aimed to study the impact of operating theatre critical event checklists on medical management and teamwork during whole-team operating theatre crisis simulations staged in a surgical daycare facility. We studied 56 simulation encounters (without and with a checklist available) divided between an initial session and then a retention session several months later. Medical management and teamwork were quantified via percentage adherence to key processes and the Team Emergency Assessment Measure, respectively. In the initial session, medical management was not improved by the presence of a checklist (56% without checklist vs. 62% with checklist; p = 0.50). In the retention session, teams performed significantly worse without the checklists (36% without checklist vs. 60% with checklist; p = 0.04). We did not observe a change in non-technical skills in the presence of a checklist in either the initial or retention sessions (68% without checklist vs. 69% with checklist (p = 0.94) and 69% without checklist vs. 65% with checklist (p = 0.36), respectively). Critical events checklists do not improve medical management or teamwork during simulated operating theatre crises in an ambulatory surgical daycare setting.

A first report of Pseudosuccinea columella (Say, 1817), an alien intermediate host for liver fluke, in Malawi.

Starting in October 2021, quarterly malacological surveys have been undertaken in Malawi, with the sampling of 12 specified freshwater habitats throughout a calendar year. Each survey monitors the presence of aquatic intermediate snail hosts of medical and veterinary importance. In March 2023, the alien lymnaeid species Pseudosuccinea columella was encountered for the first time in the surveys, in Nsanje District. This species identity was later confirmed upon DNA analysis of mitochondrial ribosomal 16S sequences. In July 2023, P. columella was also noted at single sites within Mangochi and Chikwawa Districts, and again in Nsanje District, with an additional location observed. Of particular importance, our sampled location in Mangochi District was directly connected to Lake Malawi, which expands the species list of invasive molluscs in this lake. While P. columella is a well-known intermediate snail host for human and animal fascioliasis, screening collected snails for trematode cercariae, alongside molecular xenomonitoring, did not yield equivocal evidence of active fluke infection. However, the newly recognized presence of this alien intermediate snail host within Lake Malawi, and along the Shire River Valley, flags a new concern in altered local transmission potential for human and animal fascioliasis.

An alien intermediate snail host in Malawi - Orientogalba viridis (Quoy and Gaimard, 1832) - A new concern for schistosomiasis transmission in Africa?

The freshwater amphibious snail Orientogalba viridis commonly occurs in eastern Asia, on certain Pacific islands and more importantly has recently dispersed into Europe. Since this snail is now considered an invasive species, its distribution is of growing parasitological interest as an alien intermediate host for various trematodes, particularly liver flukes. As part of ongoing surveillance for snail-borne diseases in Malawi, a population of O. viridis was first observed in May 2023, alongside an alarming presence of a human schistosome cercaria. This snail population later underwent detailed morphological characterisation with both snail and parasite identities confirmed upon DNA barcoding. This seminal observation triggered more extensive local snail surveys, finding 3 further populations in separated rice paddies, with further field-caught snails (n = 465) screened for infection and a selection used for repeated experimental challenges with miracidia from Schistosoma haematobium and Schistosoma mattheei. Although no field-caught (and experimentally exposed) snail was seen to shed schistosome cercariae, molecular xenomonitoring for schistosomiasis provided tangible evidence of putative transmission potential. Our first report of O. viridis here in Malawi, and more broadly in Africa, flags a need for increased vigilance for this invasive species alongside local clarification(s) of its transmission potential for trematodiases of either medical and/or veterinary importance.

Molecular detection of Phytophthora pluvialis, the causal agent of red needle cast in Pinus radiata.

BACKGROUND: Phytophthora pluvialis was first described in 2013 and is the causal agent of red needle cast (RNC) in Pinus radiata as well as infection in Douglas fir (Pseudotsuga menziesii). A species-specific PCR is necessary for detection of this pathogen and diagnosis of RNC. OBJECTIVE: To design and validate a species-specific molecular assay for P. pluvialis using isolates from infected pine needles. METHODS: Species-specific PCR primers were generated from the ras-related GTP-binding protein 1 gene (ypt1) gene sequence, concentrating on DNA regions unique to P. pluvialis, and real-time and quantitative polymerase chain reaction (qPCR) were used to detect P. pluvialis from both artificially inoculated and naturally infected samples. RESULTS: The species-specific PCR assay was generated following P. pluvialis DNA sequence analysis. In vitro tests of the specificity of the probe-based, quantitative, polymerase chain reaction (qPCR) assay showed that no amplification was observed with other Phytophthora species including other closely-related clade 3 species, or with fungal species associated with pine or with pine DNA. The limit of detection of the qPCR assay was 2 pg/µl. When the qPCR assay was used to detect P. pluvialis in artificially-inoculated and naturally infected P. radiata needles, a PCR product was detected in all inoculated samples; the mean concentration ranges of P. pluvialis DNA in the inoculated and naturally infected samples tested were 5.9-124.5 pg/µl and 8.1-340.2 pg/µl, respectively. The assays described herein were used with serological diagnostic strips, providing the ability to identify to species level. CONCLUSIONS: The assay described herein detects P. pluvialis with high specificity and sensitivity from a range of DNA samples, including those extracted from infected plant material and serological diagnostic strips. The ability to detect and identify P. pluvialis, from infected tissues directly, provides value and practicality to diagnostics, biosecurity and research.

Tissue inhibitor of metalloproteinases-3 facilitates Fas-mediated neuronal cell death following mild ischemia.

Tissue inhibitor of metalloproteinase-3 (TIMP-3) is a natural inhibitor of metalloproteinases involved in matrix degradation and ectodomain shedding of many cell-surface proteins, including death receptors and/or their ligands. In the present study, we examined the role of TIMP-3 in Fas-mediated neuronal cell death following cerebral ischemia, using both gene deletion and pharmacological approaches. In culture, exposure of primary cortical neurons to 2 h of oxygen-glucose deprivation (OGD) resulted in delayed neuronal cell death that was dependent on activation of the death receptor, Fas. Cortical cultures derived from timp-3(-/-) mice displayed partial resistance against OGD-induced neuronal cell death and also displayed increased shedding of Fas ligand (FasL) into the culture media, compared to wild-type control cultures. Both the increased neuroprotection and increased FasL shedding in timp-3(-/-) cultures were reversed by addition of exogenous metalloproteinase inhibitors, recombinant TIMP-3 or GM6001. In vivo, timp-3(-/-) mice showed marked resistance to a brief (30 min) middle cerebral artery occlusion (MCAO), but were not protected against more severe lesions induced by 90 min of MCAO. These studies demonstrate that TIMP-3 facilitates Fas-mediated neuronal cell death following OGD and plays a pro-apoptotic role in mild cerebral ischemia.

A review of assistive technologies for people with Parkinson's disease.

The population is aging and with this, the incidence of age related diseases such as Alzheimer's disease (AD) and Parkinson's disease (PD) are increasing. Assistive Technology (AT) is viewed as one of the possible solutions which can be used to meet the needs of persons suffering from PD. AT can enable a person to carry out a task which otherwise they would be unable to undertake independently. An AT can have many functions which range from helping people to use a computer, to monitoring someone's condition. Within this paper we attempt to categorize the different types of AT for persons with PD. Each of the technologies will be compared and contrasted and an overview of what is currently available presented. The paper concludes with some visionary comments on how the current levels of AT may change in the future.

An optimized, clinically relevant mouse model of cisplatin-induced ototoxicity.

Cisplatin-induced ototoxicity results in significant, permanent hearing loss in pediatric and adult cancer survivors. Elucidating the mechanisms underlying cisplatin-induced hearing loss as well as the development of therapies to reduce and/or reverse cisplatin ototoxicity have been impeded by suboptimal animal models. Clinically, cisplatin is most commonly administered in multi-dose, multi-cycle protocols. However, many animal studies are conducted using single injections of high-dose cisplatin, which is not reflective of clinical cisplatin administration protocols. Significant limitations of both high-dose, single-injection protocols and previous multi-dose protocols in rodent models include high mortality rates and relatively small changes in hearing sensitivity. These limitations restrict assessment of both long-term changes in hearing sensitivity and effects of potential protective therapies. Here, we present a detailed method for an optimized mouse model of cisplatin ototoxicity that utilizes a multi-cycle administration protocol that better approximates the type and degree of hearing loss observed clinically. This protocol results in significant hearing loss with very low mortality. This mouse model of cisplatin ototoxicity provides a platform for examining mechanisms of cisplatin-induced hearing loss as well as developing therapies to protect the hearing of cancer patients receiving cisplatin therapy.

Partner notification in pregnant women with HIV: findings from three inner-city clinics.

British HIV Association guidelines recommend that all HIV-positive pregnant women should be encouraged to disclose their HIV infection to their partner and that this should be viewed as a process rather than an event. The aim of this study was to describe local practice of partner notification (PN) and patterns of disclosure in a group of HIV-positive women in an antenatal setting. A retrospective case note and local pregnancy database review was undertaken. Women who had accessed specialist HIV antenatal care at one of three east London hospitals with an expected delivery date between 1 March 2004 and 30 June 2006 were identified. In total, 145 women were identified. HIV status had not been disclosed to a partner in 19% (n=27) of case notes reviewed. There was no documented discussion about PN in 18% (n=26) of case notes. Forty-three per cent (n=62) of case notes documented that the male partner had accessed HIV testing after PN was discussed. All HIV-positive pregnant women should have a documented discussion about PN. Concurrent HIV testing offered to both partners may improve HIV testing uptake in male partners and should be explored further. Care plans should include screening for intimate partner violence and housing problems; referral pathways should be established clearly when involving other agencies.

Variations in human urinary O-hydroxylysyl glycoside levels and their relationship to collagen metabolism.

Two O-hydroxylysyl glycosides, Hyl-Gal-Glc and Hyl-Gal, have been isolated from normal human urine and shown to be identical to two glycosides isolated from alkaline hydrolysates of collagen. A relatively sample and reproducible analytical procedure has been devised to measure the levels of these glycosides in human urine. By the use of this procedure it was shown that a normal diet has only a small effect on 24-hr urinary excretion levels of these glycosides indicating an endogenous origin. Urinary glycoside levels appear to be highest in children, roughly paralleling collagen turnover as indicated by urinary hydroxyproline levels. Collagen turnover equivalents calculated from urinary hydroxylysyl glycoside levels were found to be significantly larger than collagen turnover equivalents calculated from urinary hydroxyproline levels. This suggests that urinary glycosides are more quantitative indicators of collagen metabolism than urinary hydroxyproline. The ratio of Hyl-Gal-Glc to Hyl-Gal was measured in urines of diseased as well as normal individuals and a bimodal distribution was found. Alkaline hydrolysates of different human connective tissue collagens showed that only bone collagen, of the collagens examined, had a low ratio of Hyl-Gal-Glc to Hyl-Gal compared to human urine. Other collagens examined had higher ratios than found in human urine. On the basis of these results it is postulated that the bimodal distribution of glycoside ratios represents two populations of collagen turnover, the lower ratio population having a high bone collagen turnover, the lower ratio population having a high bone collagen turnover relative to the second population. Examination of the types of subjects making up the two populations supports this hypothesis. These data suggest that urinary O-hydroxylysyl glycoside excretion, in addition to providing a more quantitative estimate of collagen turnover than urinary hydroxyproline, may prove to be of value as a specific means of studying the metabolism of bone collagen.

Collagen-mediated platelet aggregation. Evidence for multivalent interactions of intermediate specificity between collagen and platelets.

We have shown previously that periodate oxidation of collagen carbohydrate does not affect its ability to aggregate platelets. We now describe an additional characterization of periodate-modified collagen which demonstrates that collagen devoid of intact carbohydrate is fully capable of fibril formation, and we confirm its capacity to initiate platelet aggregation. Furthermore, we demonstrate that the platelet aggregating abilities of Types I, II, and III fibrillar collagen are quite similar despite differences in carbohydrate content and amino acid sequence. We also demonstrate that monomeric, pepsin-solubilized Type I human collagen is ineffective inhibiting aggregation by performed fibrils derived from the same molecule, thus establishing that the affinity of platelets for collagen depends upon prior polymerization of collagen. We interpret these and other findings to demonstrate that the hydroxylysyl glycoside regions of collagen are not highly specific sites involved in platelet-collagen interactions leading to "physiological" aggregation, and that the possibility must be considered that multiple interactions involving collagen sites of comparatively low structural specificity may be the initiating events in release of platelet ADP and the ensuing aggregation.

Oxidized low density lipoproteins cause contraction and inhibit endothelium-dependent relaxation in the pig coronary artery.

The direct vasoactive effects of native and oxidatively modified low density lipoproteins as well as their effects on endothelium-dependent relaxations to 5-hydroxytryptamine were studied in isolated rings of pig right coronary artery. Slowly developing contractions were caused by native low density lipoproteins (100 micrograms protein/ml). The contractions were more pronounced in the absence than in the presence of the trace metal chelator, EDTA, and coincided with the formation of lipid peroxides during the response. The lipophilic antioxidant, butylated hydroxytoluene, prevented the oxidation of, and contraction to, native low density lipoproteins. Low density lipoproteins oxidized by exposure to copper contracted coronary arteries more rapidly with a threshold of only 1 micrograms protein/ml, but with a similar maximal contraction at 100 micrograms protein/ml. Superoxide dismutase inhibited the contraction to native low density lipoproteins, but not to oxidized low density lipoproteins. Catalase blocked contractions to both native and oxidized low density lipoproteins. Contractions to oxidized low density lipoproteins were unaffected by indomethacin, but were abolished by removal of the endothelium or by inhibitors of endothelium-derived relaxing factor. Oxidized low density lipoproteins but not native low density lipoproteins inhibited endothelium-dependent relaxations to 5-hydroxytryptamine. Thus, oxidized low density lipoproteins caused endothelium-dependent coronary artery contractions which are mediated by a hydroperoxide. Contractions to native low density lipoproteins are due to their oxidation in the organ chamber by the superoxide anion radical. Oxidized, but not native, low density lipoproteins impair normal endothelial cell vasodilator function in vitro. Oxidized low density lipoproteins, important in the pathogenesis of atherosclerosis, may directly contribute to the increased risk of vasospasm seen in hypercholesterolemia and atherosclerosis.