Sociodemographic variations in the uptake of faecal immunochemical tests in primary care: a retrospective study.

BACKGROUND: Faecal immunochemical test (FIT) usage for symptomatic patients is increasing, but variations in use caused by sociodemographic factors are unknown. A clinical pathway for colorectal cancer (CRC) was introduced in primary care for symptomatic patients in November 2017. The pathway was commissioned to provide GPs with direct access to FITs. AIM: To identify whether sociodemographic factors affect FIT return in symptomatic patients. DESIGN AND SETTING: A retrospective study was undertaken in Nottingham, UK, following the introduction of FIT as triage tool in primary care. It was mandated for all colorectal referrals (except rectal bleeding or mass) to secondary care. FIT was used, alongside full blood count and ferritin, to stratify CRC risk. METHOD: All referrals from November 2017 to December 2021 were retrospectively reviewed. Sociodemographic factors affecting FIT return were analysed by multivariate logistic regression. RESULTS: A total of 35 289 (90.7%) patients returned their index FIT, while 3631 (9.3%) did not. On multivariate analysis, males were less likely to return an FIT (odds ratio [OR] 1.11, 95% confidence interval [CI] = 1.03 to 1.19). Patients aged ≥65 years were more likely to return an FIT (OR 0.78 for non-return, 95% CI = 0.72 to 0.83). Unreturned FIT more than doubled in the most compared with the least deprived quintile (OR 2.20, 95% CI = 1.99 to 2.43). Patients from Asian (OR 1.82, 95% CI = 1.58 to 2.10), Black (OR 1.21, 95% CI = 0.98 to 1.49), and mixed or other ethnic groups (OR 1.29, 95% CI = 1.05 to 1.59) were more likely to not return an FIT compared with patients from a White ethnic group. A total of 599 (1.5%) CRCs were detected; 561 in those who returned a first FIT request. CONCLUSION: FIT return in those suspected of having CRC varied by sex, age, ethnic group, and socioeconomic deprivation. Strategies to mitigate effects on FIT return and CRC detection should be considered as FIT usage expands.

Understanding colorectal cancer risk for symptomatic patients in primary care: A cohort study utilising faecal immunochemical tests and blood results in England.

BACKGROUND: A faecal immunochemical tests (FIT) cut-off of ≥10 µg Hb/g faeces is now recommended in the UK as a gateway to urgent (suspected cancer) investigation for colorectal cancer (CRC), based on an expected CRC risk threshold of 3%. AIMS: To quantify the risk of CRC at FIT cut-offs by age, haemoglobin and platelet strata. METHODS: A cohort study of a symptomatic CRC pathway based on primary care FIT tests in Nottingham, UK (November 2017-2021) with 1-year follow-up. Heat maps showed the cumulative 1-year CRC risk using Kaplan-Meier estimates. RESULTS: In total, 514 (1.5%) CRCs were diagnosed following 33,694 index FIT requests. Individuals with a FIT ≥ 10 µg Hb/g faeces had a >3% risk of CRC, except patients under the age of 40 years (CRC risk 1.45% [95% CI: 0.03%-2.86%]). Non-anaemic patients with a FIT < 100 µg Hb/g faeces had a CRC risk of <3%, except those between the age of 70 and 85 years (5.26% 95% CI: 2.72%-7.73%). Using a ≥3% CRC threshold in patients <55 years calculated using FIT, age and anaemia might allow 160-220 colonoscopies per 10,000 FITs to be re-purposed, at a cost of missing 1-2 CRCs. CONCLUSIONS: FIT alone with a single cut-off is unlikely to be a panacea for optimising CRC diagnosis, as risk varies by FIT, age and anaemia when faecal haemoglobin levels are below 100 µg Hb/g. Tailored FIT cut-offs for investigation on a CRC pathway could reduce the number of investigations needed at a 3% CRC risk threshold.

A Mozambican marine protected area provides important habitat for vulnerable pelagic sharks.

Pelagic sharks play key roles in marine ecosystems, but are increasingly threatened by human extraction, habitat degradation and mismanagement. We investigated the use of protected and unprotected coastal habitats by bull (Carcharhinus leucas) and oceanic blacktip (Carcharhinus limbatus) sharks in southern Mozambique. Five INNOVASEA VR2W-69 kHz acoustic receivers were positioned in the Bazaruto Archipelago National Park (BANP) as well as one to the south of the park's boundaries. Seven receivers were also deployed 250 km south in the Inhambane estuary and on reef sites off Praia de Tofo. Twelve bull, and six oceanic blacktip sharks, were fitted with INNOVASEA V16 acoustic tags, which generated 933 detections of bull and 12,381 detections of oceanic blacktip sharks over a period of 1391 days. A generalised additive model was used to estimate the effects of seven spatiotemporal and environmental parameters on the frequency of each species' detections. In general, calculated residency indices were highest around the locations monitored in the BANP and one unprotected location off Tofo. Both species were more abundant across the monitored sites, during the summer when water temperatures were ~ 27 °C, when the moon was < 50% illuminated, and when the tide was rising. Detections coincided with each species' reproductive season indicating that both species may be reproductively active in the BANP region. Oceanic blacktip sharks were largely resident and so fisheries management may significantly benefit their population(s) around certain reef habitats in the BANP. The low residency and seasonal detections of bull sharks indicates that they may be transient and so effective conservation may require coordination between regional fisheries managers.

Distribution of the reef manta ray Mobula alfredi and the oceanic manta ray Mobula birostris in the Philippines: a collaborative effort for conservation.

Little is known about manta ray population size, structure and connectivity in the Philippines. In collaboration with dive operators, non-governmental organizations and authorities, sightings of manta rays were collated into a single national database. Using in-water photographs and videos gathered through citizen science and dedicated research efforts, this study compiled sightings between 2004 and 2020, showing 22 separate sites throughout the archipelago with manta rays present. A total of 392 individual reef manta rays (Mobula alfredi) and 107 oceanic manta rays (Mobula birostris) were identified from the collected footage. Four specific sites in the provinces of Masbate and Palawan together hosted 89% of all identified individuals and accounted for 95% of sightings, highlighting these areas are key aggregation sites. This study also reports the movements of M. birostris within the Philippines, based on photo-identification of three individuals moving 150 km between Cebu and Masbate. Despite the growing number of recreational divers in Daanbantayan and San Jacinto, an 80% decline in M. birostris sightings was observed at these sites. To ensure effective future conservation, it is recommended that efforts focus on the identification and protection of manta ray hotspots and migratory corridors, the creation of a sustainable tourism framework and, most important, the implementation of mitigation strategies to reduce fisheries interactions.

Influence of 3-DG as a Key Precursor Compound on Aging of Lager Beers.

3-Deoxyglucosone (3-DG) is a Maillard reaction intermediate, which forms known beer aging compounds such as Strecker aldehydes. However, the role of 3-DG in beer aging stability has not been described yet. To investigate the influence of 3-DG toward beer aging stability, different concentrations of 3-DG were added to the freshly brewed beer at the beginning of storage. Analysis of well-known degradation products of 3-DG such as 3-deoxygalactosone (HPLC-UV), 5-hydroxymethylfurfural (HPLC-UV), Strecker aldehydes (GC-MS), and free glycated amino acids (HPLC-MS/MS) during beer aging revealed that a higher initial 3-DG concentration increases the formation of the products. In this study, the significant importance of 3-DG as a key precursor compound in beer aging has been shown, especially the increase of Strecker aldehydes.

Choice of faecal immunochemical test matters: comparison of OC-Sensor and HM-JACKarc, in the assessment of patients at high risk of colorectal cancer.

OBJECTIVES: Currently, NICE recommends the use of faecal immunochemical test (FIT) at faecal haemoglobin concentrations (f-Hb) of 10 µg Hb/g faeces to stratify for colorectal cancer (CRC) risk in symptomatic populations. This f-Hb cut-off is advised across all analysers, despite the fact that a direct comparison of analyser performance, in a clinical setting, has not been performed. METHODS: Two specimen collection devices (OC-Sensor, OC-S; HM-JACKarc, HM-J) were sent to 914 consecutive individuals referred for follow up due to their increased risk of CRC. Agreement of f-Hb around cut-offs of 4, 10 and 150 µg Hb/g faeces and CRC detection rates were assessed. Two OC-S devices were sent to a further 114 individuals, for within test comparisons. RESULTS: A total of 732 (80.1%) individuals correctly completed and returned two different FIT devices, with 38 (5.2%) CRCs detected. Median f-Hb for individuals diagnosed with and without CRC were 258.5 and 1.8 µg Hb/g faeces for OC-S and 318.1 and 1.0 µg Hb/g faeces for HM-J respectively. Correlation of f-Hb results between OC-S/HM-J over the full range was rho=0.74, p<0.001. Using a f-Hb of 4 µg Hb/g faeces for both tests found an agreement of 88.1%, at 10 µg Hb/g faeces 91.7% and at 150 µg Hb/g faeces 96.3%. A total of 114 individuals completed and returned two OC-S devices; correlation across the full range was rho=0.98, p<0.001. CONCLUSIONS: We found large variations in f-Hb when different FIT devices were used, but a smaller variation when the same FIT device was used. Our data suggest that analyser-specific f-Hb cut-offs are applied with regard to clinical decision making, especially at lower f-Hb.

Temporal persistence of after-effects in the n-1 replication task.

In line with the theory of event coding, many studies on tool use show that perceived visual and haptic information interacts with action execution. In two experiments, we investigated the temporal persistence of after-effects within an event file, and after-effects in temporally overlapping event files with the n-1 replication task. Each trial consisted of two phases: In phase 1, participants moved a cursor with a pen on a covered tablet while a gain varied the relation between hand and cursor amplitude (Experiment 1). In phase 2, participants replicated the hand amplitude of phase 1 of the previous trial without visual feedback. Any systematic over- and undershoot would be indicative for after-effects. When the cursor amplitude varied and the hand amplitude remained constant, we did not find any after-effects but adjustment of the internal model. For varying hand amplitudes, after-effects appeared in terms of a contrast and assimilation effect between temporally overlapping event files and within an event file, respectively. In Experiment 2, we confirmed that the observed pattern of over- and undershoots fully reflect assimilation/contrast due to perception-action interaction. The findings extend the current view on the temporal stability of short-term binding in sensorimotor transformation tasks: In the n-1 replication task, after-effects appeared only in trials with varying hand amplitudes. We replicated the contrast effect and assimilation effect, and the assimilation effect persisted for up to approximately 20 s.

Isoform-specific Ras signaling is growth factor dependent.

HRAS, NRAS, and KRAS isoforms are almost identical proteins that are ubiquitously expressed and activate a common set of effectors. In vivo studies have revealed that they are not biologically redundant; however, the isoform specificity of Ras signaling remains poorly understood. Using a novel panel of isogenic SW48 cell lines endogenously expressing wild-type or G12V-mutated activated Ras isoforms, we have performed a detailed characterization of endogenous isoform-specific mutant Ras signaling. We find that despite displaying significant Ras activation, the downstream outputs of oncogenic Ras mutants are minimal in the absence of growth factor inputs. The lack of mutant KRAS-induced effector activation observed in SW48 cells appears to be representative of a broad panel of colon cancer cell lines harboring mutant KRAS. For MAP kinase pathway activation in KRAS-mutant cells, the requirement for coincident growth factor stimulation occurs at an early point in the Raf activation cycle. Finally, we find that Ras isoform-specific signaling was highly context dependent and did not conform to the dogma derived from ectopic expression studies.

The neuroendocrine phenotype of gastric myofibroblasts and its loss with cancer progression.

Stromal cells influence cancer progression. Myofibroblasts are an important stromal cell type, which influence the tumour microenvironment by release of extracellular matrix (ECM) proteins, proteases, cytokines and chemokines. The mechanisms of secretion are poorly understood. Here, we describe the secretion of marker proteins in gastric cancer and control myofibroblasts in response to insulin-like growth factor (IGF) stimulation and, using functional genomic approaches, we identify proteins influencing the secretory response. IGF rapidly increased myofibroblast secretion of an ECM protein, TGFßig-h3. The secretory response was not blocked by inhibition of protein synthesis and was partially mediated by increased intracellular calcium (Ca(2+)). The capacity for evoked secretion was associated with the presence of dense-core secretory vesicles and was lost in cells from patients with advanced gastric cancer. In cells responding to IGF-II, the expression of neuroendocrine marker proteins, including secretogranin-II and proenkephalin, was identified by gene array and LC-MS/MS respectively, and verified experimentally. The expression of proenkephalin was decreased in cancers from patients with advanced disease. Inhibition of secretogranin-II expression decreased the secretory response to IGF, and its over-expression recovered the secretory response consistent with a role in secretory vesicle biogenesis. We conclude that normal and some gastric cancer myofibroblasts have a neuroendocrine-like phenotype characterized by Ca(2+)-dependent regulated secretion, dense-core secretory vesicles and expression of neuroendocrine marker proteins; loss of the phenotype is associated with advanced cancer. A failure to regulate myofibroblast protein secretion may contribute to cancer progression.

Thresher sharks use tail-slaps as a hunting strategy.

The hunting strategies of pelagic thresher sharks (Alopias pelagicus) were investigated at Pescador Island in the Philippines. It has long been suspected that thresher sharks hunt with their scythe-like tails but the kinematics associated with the behaviour in the wild are poorly understood. From 61 observations recorded by handheld underwater video camera between June and October 2010, 25 thresher shark shunting events were analysed. Thresher sharks employed tail-slaps to debilitate sardines at all times of day. Hunting events comprised preparation, strike, wind-down recovery and prey item collection phases, which occurred sequentially. Preparation phases were significantly longer than the others, presumably to enable a shark to windup a tail-slap. Tail-slaps were initiated by an adduction of the pectoral fins, a manoeuvre that changed a thresher shark's pitch promoting its posterior region to lift rapidly, and stall its approach. Tail-slaps occurred with such force that they may have caused dissolved gas to diffuse out of the water column forming bubbles. Thresher sharks were able to consume more than one sardine at a time, suggesting that tail-slapping is an effective foraging strategy for hunting schooling prey. Pelagic thresher sharks appear to pursue sardines opportunistically by day and night, which may make them vulnerable to fisheries. Alopiids possess specialist pectoral and caudal fins that are likely to have evolved, at least in part, for tail-slapping. The evidence is now clear; thresher sharks really do hunt with their tails.

The impact of telehealth support for patients with diabetes or chronic obstructive pulmonary disease on unscheduled secondary care utilisation: a service evaluation.

BACKGROUND: Telehealth has been promoted as an adjunct to managing patients with long-term conditions. It has been used in various settings and for different disease groups. However, robust evidence for the efficacy of telehealth is currently lacking. OBJECTIVES: To evaluate the impact of a telehealth service on emergency admissions and emergency department (ED) attendances. METHODS: We evaluated a telehealth service providing supported self-management to patients that was implemented in Nottingham City. Two groups of patients ('graduates' of the Nottingham telehealth service and service 'decliners') were compared for two periods; 2009 (pre-service implementation) and 2011. Eighty-nine pairs of graduates and decliners were identified who were matched for age and sex. The number and cost of emergency admissions and ED attendances for these patients were then collated and analysed. RESULTS: Graduates had significantly fewer emergency admissions and ED attendances compared with decliners in 2011. However, differences of a similar magnitude in emergency admissions and ED attendances were found in 2009. Telehealth service users were likely to be qualitatively different from decliners, reflecting a degree of self-selection. This suggests that decliners were more likely to have a confounding reason for not engaging with telehealth, such as greater disease severity. CONCLUSIONS: This service review found no evidence that the Nottingham telehealth service has had a significant impact on secondary care utilisation in the short term. Longer term follow up is needed to establish conclusively whether telehealth initiatives like the Nottingham telehealth service does lead to tangible patient benefits and provide value for money.

Oceanic sharks clean at coastal seamount.

Interactions between pelagic thresher sharks (Alopias pelagicus) and cleaner wrasse were investigated at a seamount in the Philippines. Cleaning associations between sharks and teleosts are poorly understood, but the observable interactions seen at this site may explain why these mainly oceanic sharks regularly venture into shallow coastal waters where they are vulnerable to disturbance from human activity. From 1,230 hours of observations recorded by remote video camera between July 2005 and December 2009, 97 cleaner-thresher shark events were analyzed, 19 of which were interrupted. Observations of pelagic thresher sharks interacting with cleaners at the seamount were recorded at all times of day but their frequency declined gradually from morning until evening. Cleaners showed preferences for foraging on specific areas of a thresher shark's body. For all events combined, cleaners were observed to conduct 2,757 inspections, of which 33.9% took place on the shark's pelvis, 23.3% on the pectoral fins, 22.3% on the caudal fin, 8.6% on the body, 8.3% on the head, 2.1% on the dorsal fin, and 1.5% on the gills respectively. Cleaners did not preferentially inspect thresher sharks by time of day or by shark sex, but there was a direct correlation between the amount of time a thresher shark spent at a cleaning station and the number of inspections it received. Thresher shark clients modified their behavior by "circular-stance-swimming," presumably to facilitate cleaner inspections. The cleaner-thresher shark association reflected some of the known behavioral trends in the cleaner-reef teleost system since cleaners appeared to forage selectively on shark clients. Evidence is mounting that in addition to acting as social refuges and foraging grounds for large visiting marine predators, seamounts may also support pelagic ecology by functioning as cleaning stations for oceanic sharks and rays.

[Osteoid osteoma of the wrist joint resembling tenosynovitis].

Osteoid osteoma of bones of the wrist joint is a relatively rare lesion. This article presents a series of three patients, one with osteoid osteoma of the styloid process of the radius and two with osteoid osteoma of the capitate bone. All of them had clinical symptoms resembling those of stenosing tenosynovitis of the wrist joint. X-rays, tomography and bone scan revealed the characteristic findings of osteoid osteoma. Histological examination confirmed the diagnosis. Treatment consisted of "en bloc" excision of these tumors. Following surgery patients were asymptomatic and had normal mobility of the affected wrist. In the first patient this has been maintained for the succeeding 27 years. It is suggested that in any case of persistent unexplained pain of the wrist or clinical symptoms resembling those of tenosynovitis, osteoid osteoma of the styloid process of the radius or of the carpal bones should also be included in the differential diagnosis. The recommended treatment of osteoid osteoma is "en bloc" excision of this tumour in the affected bone, resulting in complete relief of pain and absence of functional disturbances.