Predictive Value of EGFR-PI3K-AKT-mTOR-Pathway Inhibitor Biomarkers for Head and Neck Squamous Cell Carcinoma:A Systematic Review

BACKGROUND: Understanding molecular pathogenesis of head and neck squamous cell carcinomas (HNSCC) has considerably improved in the last decades. As a result, novel therapeutic strategies have evolved, amongst which are epidermal growth factor receptor (EGFR)-targeted therapies. With the exception of cetuximab, targeted therapies for HNSCC have not yet been introduced into clinical practice. One important aspect of new treatment regimes in clinical practice is presence of robust biomarkers predictive for therapy response.METHODS: We performed a systematic search in PubMed, Embase and the Cochrane library. Articles were included if they investigated a biomarker for targeted therapy in the EGFR-PI3K-AKT-mTOR-pathway.RESULTS: Of 83 included articles, 52 were preclinical and 33 were clinical studies (two studies contained both a preclinical and a clinical part). We classified EGFR pathway inhibitor types and investigated the type of biomarker (biomarker on epigenetic, DNA, mRNA or protein level).CONCLUSION: Several EGFR-PI3K-AKT-mTOR-pathway inhibitor biomarkers have been researched for HNSCC but few of the investigated biomarkers have been adequately confirmed in clinical trials. A more systematic approach is needed to discover proper biomarkers as stratifying patients is essential to prevent unnecessary costs and side effects.</p

Mental healthcare goes online:Practitioners' experiences of providing mental healthcare during the COVID-19 pandemic

The outbreak of the COVID-19 pandemic has necessitated sudden and radical changes in mental health care delivery, as strict social distancing and lockdown measures were imposed in the early phases of the pandemic. Almost overnight, practitioners were forced to transfer their face-to-face care practice to online means. To understand the implications of this drastic change for mental health care, and to improve the online care offerings, an online qualitative survey was held among mental health care professionals in Netherlands (n = 51). Our findings indicate that technological and usability problems pose a significant challenge, as do difficulties to establish rapport with clients. Moreover, not all mental health issues and treatment forms are equally amenable to online interaction. In contrast, in many instances, practitioners were positive about the effectiveness of treatment, and reported flexibility, a lower threshold for contact, and lack of travel time as advantages. Their most prominent needs concern better technological, organizational, and logistical support. It is critical that these needs are acted upon by institutions and governments. In addition, current results inform future research on the improvement of e-mental health technologies

Image method in the calculation of the van der Waals force between an atom and a conducting surface

Initially, we make a detailed historical survey of van der Waals forces, collecting the main references on the subject. Then, we review a method recently proposed by Eberlein and Zietal to compute the dispersion van der Waals interaction between a neutral but polarizable atom and a perfectly conducting surface of arbitrary shape. This method has the advantage of relating the quantum problem to a corresponding classical one in electrostatics so that all one needs is to compute an appropriate Green function. We show how the image method of electrostatics can be conveniently used together with the Eberlein and Zietal mehtod (when the problem admits an image solution). We then illustrate this method in a couple of simple but important cases, including the atom-sphere system. Particularly, in our last example, we present an original result, namely, the van der Waals force between an atom and a boss hat made of a grounded conducting material.Comment: This is a pedagogical and introductory paper on van der Waals forces between an atom and a conducting surfac

Assessing professionals' adoption readiness for eMental health:Development and validation of the eMental health adoption readiness scale

BACKGROUND: The last few decades have witnessed significant advances in the development of digital tools and applications for mental health care. Despite growing evidence for their effectiveness, acceptance and use of these tools in clinical practice remain low. Hence, a validated and easy-to-use instrument for assessing professionals’ readiness to adopt eMental health (EMH) is necessary to gain further insights into the process of EMH adoption and facilitate future research on this topic. OBJECTIVE: The aim of this study is to develop and validate an instrument for assessing mental health care professionals’ readiness to adopt EMH. METHODS: Item generation was guided by literature and inputs from mental health care professionals and experts in survey development. Exploratory factor analyses were conducted on an initial set of 29 items completed by a sample of mental health care professionals (N=432); thereafter, the scale was reduced to 15 items in an iterative process. The factor structure thus obtained was subsequently tested using a confirmatory factor analysis with a second sample of mental health care professionals (N=363). The internal consistency, convergent validity, and predictive validity of the eMental Health Adoption Readiness (eMHAR) Scale were assessed. RESULTS: Exploratory factor analysis resulted in a 3-factor solution with 15 items. The factors were analyzed and labeled as perceived benefits and applicability of EMH, EMH proactive innovation, and EMH self-efficacy. These factors were confirmed through a confirmatory factor analysis. The total scale and subscales showed a good internal consistency (Cronbach α=.73-.88) along with acceptable convergent and predictive relationships with related constructs. CONCLUSIONS: The constructed eMHAR Scale showed a conceptually interpretable 3-factor structure having satisfactory characteristics and relationships with relevant concepts. Its ease of use allows for quick acquisition of data that can contribute to understanding and facilitating the process of adoption of EMH by clinical professionals

Patch: platelet transfusion in cerebral haemorrhage: study protocol for a multicentre, randomised, controlled trial

<p>Abstract</p> <p>Background</p> <p>Patients suffering from intracerebral haemorrhage have a poor prognosis, especially if they are using antiplatelet therapy. Currently, no effective acute treatment option for intracerebral haemorrhage exists. Limiting the early growth of intracerebral haemorrhage volume which continues the first hours after admission seems a promising strategy. Because intracerebral haemorrhage patients who are on antiplatelet therapy have been shown to be particularly at risk of early haematoma growth, platelet transfusion may have a beneficial effect.</p> <p>Methods/Design</p> <p>The primary objective is to investigate whether platelet transfusion improves outcome in intracerebral haemorrhage patients who are on antiplatelet treatment. The PATCH study is a prospective, randomised, multi-centre study with open treatment and blind endpoint evaluation. Patients will be randomised to receive platelet transfusion within six hours or standard care. The primary endpoint is functional health after three months. The main secondary endpoints are safety of platelet transfusion and the occurrence of haematoma growth. To detect an absolute poor outcome reduction of 20%, a total of 190 patients will be included.</p> <p>Discussion</p> <p>To our knowledge this is the first randomised controlled trial of platelet transfusion for an acute haemorrhagic disease.</p> <p>Trial registration</p> <p>The Netherlands National Trial Register (NTR1303)</p

Risk factors for atherosclerotic and medial arterial calcification of the intracranial internal carotid artery

_Background and aims:_ Calcifications of the intracranial internal carotid artery (iICA) are an important risk factor for stroke. The calcifications can occur both in the intimal and medial layer of the vascular wall. The aim of this study is to assess whether medial calcification in the iICA is differently related to risk factors for cardiovascular disease, compared to intimal calcification. _Methods:_ Unenhanced thin slice computed tomography (CT) scans from 1132 patients from the Dutch acute stroke study cohort were assessed for dominant localization of calcification (medial or intimal) by one of three observers based on established methodology. Associations between known cardiovascular risk factors (age, gender, body mass index, pulse pressure, eGFR, smoking, hypertension, diabetes mellitus, hyperlipidemia, previous vascular disease, and family history) and the dominant localization of calcifications were assessed via logistic regression analysis. _Results:_ In the 1132 patients (57% males, mean age 67.4 years [SD 13.8]), dominant intimal calcification was present in 30.9% and dominant medial calcification in 46.9%. In 10.5%, no calcification was seen. Age, pulse pressure and family history were risk factors for both types of calcification. Multivariably adjusted risk factors for dominant intimal calcification only were smoking (OR 2.09 [CI 1.27–3.44]) and hypertension (OR 2.09 [CI 1.29–3.40]) and for dominant medial calcification diabetes mellitus (OR 2.39 [CI 1.11–5.14]) and previous vascular disease (OR 2.20 [CI 1.30–3.75]). _Conclusions:_ Risk factors are differently related to the dominant localizations of calcifications, a finding that supports the hypothesis that the intimal and medial calcification represents a distinct etiology

High tie versus low tie in rectal surgery: comparison of anastomotic perfusion

Item does not contain fulltextPURPOSE: Both "high tie" (HT) and "low tie" (LT) are well-known strategies in rectal surgery. The aim of this study was to compare colonic perfusion after HT to colonic perfusion after LT. METHODS: Patients undergoing rectal resection for malignancy were included. Colonic perfusion was measured with laser Doppler flowmetry, immediately after laparotomy on the antimesenterial side of the colon segment that was to become the afferent loop (measurement A). This measurement was repeated after rectal resection (measurement B). The blood flow ratios (B/A) were compared between the HT group and the LT group. RESULTS: Blood flow was measured in 33 patients, 16 undergoing HT and 17 undergoing LT. Colonic blood flow slightly decreased in the HT group whereas the flow increased in the LT group. The blood flow ratio was significantly higher in the LT group (1.48 vs. 0.91; p = 0.04), independent of the blood pressure. CONCLUSION: This study shows the blood flow ratio to be higher in the LT group. This suggests that anastomoses may benefit from better perfusion when LT is performed

Patients Enrolled in Large Randomized Clinical Trials of Antiplatelet Treatment for Prevention After Transient Ischemic Attack or Ischemic Stroke Are Not Representative of Patients in Clinical Practice: the Netherlands Stroke Survey

Background and Purpose—Many randomized clinical trials have evaluated the benefit of long-term use of antiplatelet drugs in reducing the risk of new vascular events in patients with a recent transient ischemic attack or ischemic stroke. Evidence from these trials forms the basis for national and international guidelines for the management of nearly all such patients in clinical practice. However, abundant and strict enrollment criteria may limit the validity and the applicability of results of randomized clinical trials to clinical practice. We estimated the eligibility for participation in landmark trials of antiplatelet drugs of an unselected group of patients with stroke or transient ischemic attack from a national stroke survey. Methods—Nine hundred seventy-two patients with transient ischemic at

A Spitzer Transmission Spectrum for the Exoplanet GJ 436b, Evidence for Stellar Variability, and Constraints on Dayside Flux Variations

In this paper we describe a uniform analysis of eight transits and eleven secondary eclipses of the extrasolar planet GJ 436b obtained in the 3.6, 4.5, and 8.0 micron bands using the IRAC instrument on the Spitzer Space Telescope between UT 2007 June 29 and UT 2009 Feb 4. We find that the best-fit transit depths for visits in the same bandpass can vary by as much as 8% of the total (4.7 sigma significance) from one epoch to the next. Although we cannot entirely rule out residual detector effects or a time-varying, high-altitude cloud layer in the planet's atmosphere as the cause of these variations, we consider the occultation of active regions on the star in a subset of the transit observations to be the most likely explanation. We reconcile the presence of magnetically active regions with the lack of significant visible or infrared flux variations from the star by proposing that the star's spin axis is tilted with respect to our line of sight, and that the planet's orbit is therefore likely to be misaligned. These observations serve to illustrate the challenges associated with transmission spectroscopy of planets orbiting late-type stars; we expect that other systems, such as GJ 1214, may display comparably variable transit depths. Our measured 8 micron secondary eclipse depths are consistent with a constant value, and we place a 1 sigma upper limit of 17% on changes in the planet's dayside flux in this band. Averaging over the eleven visits gives us an improved estimate of 0.0452% +/- 0.0027% for the secondary eclipse depth. We combine timing information from our observations with previously published data to produce a refined orbital ephemeris, and determine that the best-fit transit and eclipse times are consistent with a constant orbital period. [ABRIDGED]Comment: 26 pages, 18 figures, 7 tables in emulateapj format. Accepted for publication in Ap