tinyVAST: R package with an expressive interface to specify lagged and simultaneous effects in multivariate spatio-temporal models

Multivariate spatio-temporal models are widely applicable, but specifying their structure is complicated and may inhibit wider use. We introduce the R package tinyVAST from two viewpoints: the software user and the statistician. From the user viewpoint, tinyVAST adapts a widely used formula interface to specify generalized additive models, and combines this with arguments to specify spatial and spatio-temporal interactions among variables. These interactions are specified using arrow notation (from structural equation models), or an extended arrow-and-lag notation that allows simultaneous, lagged, and recursive dependencies among variables over time. The user also specifies a spatial domain for areal (gridded), continuous (point-count), or stream-network data. From the statistician viewpoint, tinyVAST constructs sparse precision matrices representing multivariate spatio-temporal variation, and parameters are estimated by specifying a generalized linear mixed model (GLMM). This expressive interface encompasses vector autoregressive, empirical orthogonal functions, spatial factor analysis, and ARIMA models. To demonstrate, we fit to data from two survey platforms sampling corals, sponges, rockfishes, and flatfishes in the Gulf of Alaska and Aleutian Islands. We then compare eight alternative model structures using different assumptions about habitat drivers and survey detectability. Model selection suggests that towed-camera and bottom trawl gears have spatial variation in detectability but sample the same underlying density of flatfishes and rockfishes, and that rockfishes are positively associated with sponges while flatfishes are negatively associated with corals. We conclude that tinyVAST can be used to test complicated dependencies representing alternative structural assumptions for research and real-world policy evaluation

Evaluation of rockfish abundance in untrawlable habitat: combining acoustic and complementary sampling tools

Rockfishes (Sebastes spp.) are an important component of North Pacific marine ecosystems and commercial fisheries. Because the rocky, high-relief substrate that rockfishes often inhabit is inaccessible to standard survey trawls, population abundance assessments for many rockfish species are difficult. As part of a large study to classify substrate and compare complementary sampling tools, we investigated the feasibility of using an acoustic survey in conjunction with a lowered stereo-video camera, a remotely operated vehicle, and a modified bottom trawl to estimate rockfish biomass in untrawlable habitat. The Snakehead Bank south of Kodiak Island, Alaska, was surveyed repeatedly over 4 days and nights. Dusky rockfish (S. variabilis), northern rockfish (S. polyspinis), and harlequin rockfish (S. variegatus) were the most abundant species observed on the bank. Backscatter attributed to rockfish were collected primarily near the seafloor at a mean height off the bottom of 1.5 m. Total rockfish backscatter and the height of backscatter off the bottom did not differ among survey passes or between night and day. Biomass estimates for the 41 square nautical-mile area surveyed on this small, predominantly untrawlable bank were 2350 metric tons (t) of dusky rockfish, 331 t of northern rockfish, and 137 t of harlequin rockfish. These biomass estimates are 5–60 times the density estimated for these rockfish species by a regularly conducted bottom trawl survey covering the bank and the surrounding shelf. This finding shows that bottom trawl surveys can underestimate the abundance of rockfishes in untrawlable areas and, therefore, may underestimate overall population abundance for these species

Characterisation of DOG-1 expression in salivary gland tumours and comparison with myoepithelial markers

DOG1 is an established diagnostic marker for gastrointestinal stromal tumours (GIST), but has been reported in salivary gland tumours (SGT) as an acinar and intercalated duct marker. However, its specificity and distribution is not well established. The aim of this study was to evaluate the diagnostic utility of DOG-1 expression in SGT in addition to comparing it with myoepithelial markers. Normal salivary tissue and SGT (n = 184) were examined for expression of DOG1 and a range of myoepithelial markers. SGT included: acinic cell carcinoma (ACC, n = 15), secretory carcinoma (SC, n = 9), pleomorphic adenoma (PA, n = 49), carcinoma ex-PA (Ca ex-PA, n = 11), adenoid cystic carcinoma (AdCC, n = 20), polymorphous adenocarcinoma (PAC, n = 6), myoepithelioma (n = 6), myoepithelial carcinoma (MC, n = 2), basal cell adenoma (BCA, n = 14), canalicular adenoma (CA, n = 19), mucoepidermoid carcinoma (MEC, n = 11), oncocytoma (n = 2), adenocarcinoma NOS (AdNOS, n = 4), basal cell adenocarcinoma (BCAC, n = 2), salivary duct carcinoma (SDC, n = 3) and papillary cystadenocarcinoma (PCAC, n = 1). Normal acini and ACC (14/15) showed strong luminal DOG1 staining; SC were largely negative with only focal expression in 3/9 cases. Luminal staining was seen in PA (14/49), PAC (4/6), Ca ex-PA (4/11) and AdCC (6/20). 8/11 MEC showed luminal and/or mucous cell staining. No staining was seen in myoepithelioma, MC, CA, adNOS and BCAC. BCA showed strong staining of myoepithelial cells in some cases (5/14). Variable myoepithelial DOG1 staining was seen in PA, Ca ex PA, BCA, SDC and PCAC which was not as consistent as myoepithelial markers such as calponin, p63 and αSMA. Absence of DOG1 can differentiate ACC from SC, but staining is variable in PA, PLGA and Ca ex-PA. Myoepithelial staining in some tumours but not in normal gland suggests a wider distribution in SGT than originally envisaged

Microcribriform Adenocarcinoma of Salivary Glands: A Unique Tumor Entity Characterized by an SS18::ZBTB7A Fusion

The landscape of salivary gland carcinomas is ever-changing, with a growing list of new tumors and newly elucidated variants of well-known tumor entities. The routine use of next-generation sequencing has been instrumental in identifying novel fusions and tumor entities, which has helped bring the classification to a more objective and evidenced-based model. However, morphology remains critical in assessing the validity of these novel molecular findings, and most importantly, in assessing which of these findings will have an impact on the prognosis and treatment decisions for patients. The recognition of microsecretory adenocarcinoma (MSA) as a distinct low-grade malignancy of salivary glands, underpinned by MEF2C::SS18, and a single possibly related case of SS18::ZBTB7A, recently expanded this growing list of distinctive tumors. It was not until now, however, that the morphology of the latter case was known to be unique and reproducible. The authors have now seen 4 of these distinctive tumors that show a combination of distinctive oncocytic cells forming compact glandular growth as well as amphophilic cells forming tubular growth, and suggest the appellation "microcribriform adenocarcinoma" (MCA). So far, these tumors appear to preferentially occur in nonoral sites (2 parotid, 1 submandibular gland, and 1 bronchial seromucous glands). By immunohistochemistry, they express S100 and SOX-10 with focal outer myoepithelial cells marked by circumferential p63, p40, and smooth muscle actin staining around some of the nests and tubules. The tumors show infiltrative growth within a hyalinized and myxoid stroma. Cytologically, they appear generally low grade, similar to MSA. The morphologic and molecular uniformity of these 4 microcribriform adenocarcinoma cases warrants their recognition, and while related to MSA, they are sufficiently different to be classified as a distinct tumor. So far, in limited follow-up, these tumors appear to be relatively indolent

Antibiotic Review Kit for Hospitals (ARK-Hospital): study protocol for a stepped-wedge cluster-randomised controlled trial

Background To ensure patients continue to get early access to antibiotics at admission, while also safely reducing antibiotic use in hospitals, one needs to target the continued need for antibiotics as more diagnostic information becomes available. UK Department of Health guidance promotes an initiative called ‘Start Smart then Focus’: early effective antibiotics followed by active ‘review and revision’ 24–72 h later. However in 2017, &lt; 10% of antibiotic prescriptions were discontinued at review, despite studies suggesting that 20–30% of prescriptions could be stopped safely. Methods/design Antibiotic Review Kit for Hospitals (ARK-Hospital) is a complex ‘review and revise’ behavioural intervention targeting healthcare professionals involved in antibiotic prescribing or administration in inpatients admitted to acute/general medicine (the largest consumers of non-prophylactic antibiotics in hospitals). The primary study objective is to evaluate whether ARK-Hospital can safely reduce the total antibiotic burden in acute/general medical inpatients by at least 15%. The primary hypotheses are therefore that the introduction of the behavioural intervention will be non-inferior in terms of 30-day mortality post-admission (relative margin 5%) for an acute/general medical inpatient, and superior in terms of defined daily doses of antibiotics per acute/general medical admission (co-primary outcomes). The unit of observation is a hospital organisation, a single hospital or group of hospitals organised with one executive board and governance framework (National Health Service trusts in England; health boards in Northern Ireland, Wales and Scotland). The study comprises a feasibility study in one organisation (phase I), an internal pilot trial in three organisations (phase II) and a cluster (organisation)-randomised stepped-wedge trial (phase III) targeting a minimum of 36 organisations in total. Randomisation will occur over 18 months from November 2017 with a further 12 months follow-up to assess sustainability. The behavioural intervention will be delivered to healthcare professionals involved in antibiotic prescribing or administration in adult inpatients admitted to acute/general medicine. Outcomes will be assessed in adult inpatients admitted to acute/general medicine, collected through routine electronic health records in all patients. Discussion ARK-Hospital aims to provide a feasible, sustainable and generalisable mechanism for increasing antibiotic stopping in patients who no longer need to receive them at ‘review and revise’. Trial registration ISRCTN Current Controlled Trials, ISRCTN12674243. Registered on 10 April 2017.</p