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Furthermore, imaging studies characterized TAK-164 uptake and activity and showed positive relationships between GCC expression and tumor uptake which correlated with antitumor activity. Collectively, our data suggest that TAK-164 is highly active in multiple GCC-positive tumors including those refractory to TAK-264, a GCC-targeted auristatin ADC. A strong relationship between uptake of 89Zr-labeled TAK-164, levels of GCC expression and, most notably, response to TAK-164 therapy in GCC-expressing xenografts and PHTX models. These data supported the clinical development of TAK-164 as part of a first-in-human clinical trial (NCT03449030).The national implementation groups of early warning systems in the UK and Ireland have identified a need to understand implementation, adoption and maintenance of these complex interventions. The literature on how to implement, scale, spread and sustain these systems is sparse. We describe a successful adoption and maintenance over 10 years of a paediatric early warning system as a sociotechnical intervention using the Nonadoption, Abandonment, Challenges to the Scale-Up, Spread, and Sustainability Framework for Health and Care Technologies. The requirement for iterative processes within environment, culture, policy, human action and the wider system context may explain the possible reasons for improved outcomes in small-scale implementation and meta-analyses that are not reported in multicentre randomised control trials of early warning systems.
Nocturnal pulse oximetry can be used to screen for obstructive sleep apnoea (OSA) using the McGill Oximetry Score (MOS). The MOS has a time threshold for a technically adequate study of 6 hours. It has been suggested that one night of oximetry is sufficient to screen for OSA using the MOS.

(1) To evaluate night-to-night variation of the MOS. (2) To determine the impact of recording three nights of oximetry on the screening yield for OSA. (3) To explore whether useful MOS data are discarded when a threshold of 6 hours of oximetry recording is used.

A retrospective study of nocturnal pulse oximetry done at home over three consecutive nights in paediatric patients with suspected OSA. Studies were scored (MOS) using thresholds of ≥6 and ≥4 hours of recording.

A total of 329 patients were studied. MOS scores over three nights showed only fair to moderate agreement. On the first night 126 patients (38%) screened positive for OSA. When three nights of oximetry were done 195 patients (59%) screened positive on at least one of the nights. There were 48 patients with studies of between 4 and 6 hours duration on one or more nights. If these studies are scored 20 patients (42%) would screen positive for OSA on at least one night based on scoring these studies alone.

One night of oximetry screening may not be sufficient to screen for OSA. Lowering the time threshold to ≥4 hours may increase the screening capability of nocturnal oximetry.
One night of oximetry screening may not be sufficient to screen for OSA. Lowering the time threshold to ≥4 hours may increase the screening capability of nocturnal oximetry.
Electronic health records (EHRs) are routinely used to identify family violence, yet reliable evidence of their validity remains limited. We conducted a systematic review and meta-analysis to evaluate the positive predictive values (PPVs) of coded indicators in EHRs for identifying intimate partner violence (IPV) and child maltreatment (CM), including prenatal neglect.

We searched 18 electronic databases between January 1980 and May 2020 for studies comparing any coded indicator of IPV or CM including prenatal neglect defined as neonatal abstinence syndrome (NAS) or fetal alcohol syndrome (FAS), against an independent reference standard. see more We pooled PPVs for each indicator using random effects meta-analyses.

We included 88 studies (3 875 183 individuals) involving 15 indicators for identifying CM in the prenatal period and childhood (0-18 years) and five indicators for IPV among women of reproductive age (12-50 years). Based on the International Classification of Disease system, the pooled PPV was over 80% for NAS (16 studies) but lower for FAS (<40%; seven studies). For young children, primary diagnoses of CM, specific injury presentations (eg, rib fractures and retinal haemorrhages) and assaults showed a high PPV for CM (pooled PPVs 55.9%-87.8%). Indicators of IPV in women had a high PPV, with primary diagnoses correctly identifying IPV in >85% of cases.

Coded indicators in EHRs have a high likelihood of correctly classifying types of CM and IPV across the life course, providing a useful tool for assessment, support and monitoring of high-risk groups in health services and research.
Coded indicators in EHRs have a high likelihood of correctly classifying types of CM and IPV across the life course, providing a useful tool for assessment, support and monitoring of high-risk groups in health services and research.Black esophagus, also known as acute esophageal necrosis (AEN) syndrome, is a rare entity characterized by patchy or diffuse circumferential black pigmentation of the esophageal mucosa from ischemic necrosis. It may present with life-threatening upper gastrointestinal hemorrhage resulting in high mortality in immunocompromised patients. Advanced age with multiple comorbidities compounded with compromised hemodynamic states are poor prognostic factors. Findings on laboratory work-up and radiological imaging are non-specific. After initial resuscitation, endoscopic evaluation and histological examination of esophageal biopsy are diagnostic. Early recognition and aggressive resuscitation are the fundamental principles for the management of AEN and better outcome of the disease. We report a case of a 56-year-old woman with diabetes mellitus, gastro-esophageal reflux disease, and active alcohol binging who presented with hematemesis and acute epigastric pain due to AEN. This case illustrates a rare etiology of AEN due to active alcohol drinking, which may be overlooked. Physician awareness about this etiology is important as early recognition and timely management may improve survival.
D-dimer might serve as a marker of thrombogenesis and a hypercoagulable state following plaque rupture. Few studies explore the association between baseline D-dimer levels and the incidence of heart failure (HF), all-cause mortality in an acute myocardial infarction (AMI) population. We aimed to explore this association.

We enrolled 4504 consecutive patients with AMI with complete data in a prospective cohort study and explored the association of plasma D-dimer levels on admission and the incidence of HF, all-cause mortality.

Over a median follow-up of 1 year, 1112 (24.7%) patients developed in-hospital HF, 542 (16.7%) patients developed HF after hospitalisation and 233 (7.1%) patients died. After full adjustments for other relevant clinical covariates, patients with D-dimer values in quartile 3 (Q3) had 1.51 times (95% CI 1.12 to 2.04) and in Q4 had 1.49 times (95% CI 1.09 to 2.04) as high as the risk of HF after hospitalisation compared with patients in Q1. Patients with D-dimer values in Q4 had more than a twofold (HR 2.34; 95% CI 1.33 to 4.13) increased risk of death compared with patients in Q1 (p<0.001). But there was no association between D-dimer levels and in-hospital HF in the adjusted models.

D-dimer was found to be associated with the incidence of HF after hospitalisation and all-cause mortality in patients with AMI.
D-dimer was found to be associated with the incidence of HF after hospitalisation and all-cause mortality in patients with AMI.Current debates about the possible causes of depression reinforce the age-old body-mind dualism while some claim that depression is caused by psychological or societal stress, others underline that it results from a shortage of the neurotransmitter serotonin in the central nervous system. This paper shows that Michel Houellebecq's latest novel Serotonin can be read as an account of depression that goes beyond this body-mind dualism. Moreover, we will argue that his way of narrating invites us to reconsider the restorative power of narrative in 'pathography,' a genre that is a primary focus within medical humanities. The first section of the paper discusses, while drawing on Wilson's work on new materialism, that although the title of the novel Serotonin may suggest that Houellebecq takes sides with those who believe that depression is a brain disease, the protagonist of the novel suffers mainly from his gut feelings, which affects his entire embodied existence. Against the background of Merleau-Ponty's philosophy, the second section specifies this existential disruption in terms of an embodied 'I cannot.' In the third section, we make clear how Houellebecq's way of narrating-plotless and episodic-reinforces these embodied feelings of incapacity. The final section, then, traces how Houellebecq, by means of his style of writing and his choice of themes, succeeds in transferring gut feelings onto the reader. If illness narratives aim at sharing experiences of illness, the 'narrative' of depression, so we argue, had better take the form of an anti-narrative or a chaos story. Indeed, Houellebecq's anti-narrative succeeds in passing on to the reader the experience of a debilitating gut feeling, and a gradual loss of grip that manifests itself as a temporal and spatial disorientation.The severe acute respiratory syndrome coronavirus 2 (SARS-COV-2) Spike glycoprotein is solely responsible for binding to the host cell receptor and facilitating fusion between the viral and host membranes. The ability to generate viral particles pseudotyped with SARS-COV-2 Spike is useful for many types of studies, such as characterization of neutralizing antibodies or development of fusion-inhibiting small molecules. Here, we characterized the use of a codon-optimized SARS-COV-2 Spike glycoprotein for the generation of pseudotyped HIV-1, murine leukemia virus (MLV), and vesicular stomatitis virus (VSV) particles. The full-length Spike protein functioned inefficiently with all three systems but was enhanced over 10-fold by deleting the last 19 amino acids of the cytoplasmic tail. Infection of 293FT target cells was possible only if the cells were engineered to stably express the human angiotensin-converting enzyme 2 (ACE2) receptor, but stably introducing an additional copy of this receptor did not further enhogenic virus incorporated into a replication-defective viral particle that contains a sensitive reporter system. These pseudoparticles enter cells using the glycoprotein from the pathogenic virus, leading to a readout for infection. Conditions that block entry of the pathogenic virus, such as neutralizing antibodies, will also block entry of the viral pseudoparticles. However, viral glycoproteins often are not readily suited for generating pseudoparticles. Here, we describe a series of modifications that result in the production of relatively high-titer SARS-COV-2 pseudoparticles that are suitable for the detection of neutralizing antibodies from COVID-19 patients.
Therapeutic radiographers (TRs) are well placed to deliver health behaviour change advice to those living with and beyond cancer (LWBC). However, there is limited research on the opinions of TRs around delivering such advice to those LWBC. This study aimed to explore TRs' practices and facilitators in delivering advice on physical activity, healthy eating, alcohol intake, smoking and weight management.

Fifteen UK-based TRs took part in a telephone interview using a semi-structured interview guide. Data was analysed using the framework analysis method.

Emergent themes highlighted that TRs are mainly aware of the benefits of healthy behaviours in managing radiotherapy treatment related side effects, with advice provision lowest for healthy eating and physical activity. Participants identified themselves as well placed to deliver advice on improving behaviours to those LWBC, however reported a lack of knowledge as a limiting factor to doing so. The TRs reported training and knowledge as key facilitators to the delivery of advice, with a preference for online training.
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