Decisions that we make about email legitimacy can result in a pernicious threat to security of both individuals and organisations. Yet user response to phishing emails is far from uniform; some ...respond while others do not. What is the source of this diversity in decision-making? From a psychological perspective, we consider cognitive and situational influences that might explain why certain users are more susceptible than others. Alongside an email judgment task employed as a proxy for fraud susceptibility, 224 participants completed a range of cognitive tasks. In addition, we manipulated time pressure for email legitimacy judgments. We identify cognitive reflection and sensation seeking as significant, albeit modest, predictors of susceptibility. Further to this, participants asked to make quicker responses made more judgment errors. We conclude there are cognitive signatures that partially contribute to email fraud susceptibility, with implications for efforts to limit online security breaches and train secure behaviors.
Purpose
Neoadjuvant radiotherapy is commonly used in rectal cancer. When used prior to radical surgery in locally advanced disease, up to one-quarter of patients have no residual cancer at surgery ...suggesting that radical surgery was unnecessary; those with complete clinical response may be managed on a rectal-preserving ‘watch-and-wait’ pathway. In those receiving radiotherapy for early stage cancer, local excision of small volume residual or recurrent tumour is possible, but its value is unclear.
Methods
Data were collected from two institutions (UK and Denmark) which maintain prospective databases on all patients undergoing local excision by transanal endoscopic microsurgery (TEM). The study group was all patients who had TEM after neoadjuvant radiation for rectal cancer over an 11-year period.
Results
Forty-five patients had TEM after neoadjuvant radiation, 18 after short course radiotherapy (SCRT) and 27 after chemoradiotherapy (CRT). Local recurrence occurred in 13 (29%) and distant metastases in 11 (24%). Complete pathological response was noted in 10 (22%), 28% after SCRT and 19% after CRT,
p
= 0.02. However, local recurrence still occurred in 60% of those with ypT0 after SCRT. The recurrence rate may be higher in those with residual disease at TEM compared with complete responders (40 vs 30%).
Conclusion
If complete response can be determined clinically, local excision of the scar does not confer benefit, but follow-up should be maintained. If there is regrowth or residual tumour at TEM, further recurrence is common, and the benefits of TEM may not outweigh the risks, except in those unsuitable for radical surgery.
Pasta presents a challenge to microwave processing due to its unique cooking requirements. The objective of this study was to determine the effects of microwave processing on pasta physicochemical ...and mechanical properties. Fettuccine pasta was parboiled for selected times, then pasteurized using a Microwave Assisted Pasteurization System and stored under refrigeration for 1 wk. Samples were analyzed using microscopy, mechanical testing, and chemical analyses after storage. While no significant differences were observed for free amylose among fresh samples, samples parboiled for ≤6 min had significantly higher free amylose, suggesting reduced starch retrogradation. Increased heat treatment increased degree of protein polymerization, observed in microstructures as increased gluten strand thickness and network density. Firmness and extensibility increased with increased parboil time; however, extension data indicated an overall weakening of microwave‐treated pasta regardless of total cooking time. Overall, microwave pasteurization was shown to be a viable cooking method for pasta.
Practical Applications
Microwave pasteurization may be used to prepare ready‐to‐eat and heat‐and‐eat pasta dishes, providing consumers with a convenience product with a lower risk of pathogen contamination. This technology may be adapted to similar products, providing the needed lethality step for pathogens that is critical to the safety of convenience products.
Malabsorption of fat and protein contributes to poor nutritional status in people with cystic fibrosis. Impaired pancreatic function may also result in increased gastric acidity, leading in turn to ...heartburn, peptic ulcers and the impairment of oral pancreatic enzyme replacement therapy. The administration of gastric acid-reducing agents has been used as an adjunct to pancreatic enzyme therapy to improve absorption of fat and gastro-intestinal symptoms in people with cystic fibrosis. It is important to establish the evidence regarding potential benefits of drugs that reduce gastric acidity in people with cystic fibrosis. This is an update of a previously published review.
To assess the effect of drug therapies for reducing gastric acidity for: nutritional status; symptoms associated with increased gastric acidity; fat absorption; lung function; quality of life and survival; and to determine if any adverse effects are associated with their use.
We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Trials Register which comprises references identified from comprehensive electronic and non-electronic database searches, handsearches of relevant journals, abstract books and conference proceedings. Both authors double checked the reference lists of the searches Most recent search of the Group's Trials Register: 26 April 2021. On the 26 April 2021 further searches were conducted on the clinicaltrials.gov register to identify any ongoing trials that may be of relevance. The WHO ICTRP database was last searched in 2020 and is not currently available for searching due to the Covid-19 pandemic.
All randomised and quasi-randomised trials involving agents that reduce gastric acidity compared to placebo or a comparator treatment.
Both authors independently selected trials, assessed trial quality and extracted data.
The searches identified 40 trials; 17 of these, with 273 participants, were suitable for inclusion, but the number of trials assessing each of the different agents was small. Seven trials were limited to children and four trials enrolled only adults. Meta-analysis was not performed, 14 trials were of a cross-over design and we did not have the appropriate information to conduct comprehensive meta-analyses. All the trials were run in single centres and duration ranged from five days to six months. The included trials were generally not reported adequately enough to allow judgements on risk of bias. However, one trial found that drug therapies that reduce gastric acidity improved gastro-intestinal symptoms such as abdominal pain; seven trials reported significant improvement in measures of fat malabsorption; and two trials reported no significant improvement in nutritional status. Only one trial reported measures of respiratory function and one trial reported an adverse effect with prostaglandin E2 analogue misoprostol. No trials have been identified assessing the effectiveness of these agents in improving quality of life, the complications of increased gastric acidity, or survival.
Trials have shown limited evidence that agents that reduce gastric acidity are associated with improvement in gastro-intestinal symptoms and fat absorption. Currently, there is insufficient evidence to indicate whether there is an improvement in nutritional status, lung function, quality of life, or survival. Furthermore, due to the unclear risks of bias in the included trials, we are unable to make firm conclusions based on the evidence reported therein. We therefore recommend that large, multicentre, randomised controlled clinical trials are undertaken to evaluate these interventions.
Summary Background Neisseria meningitidis serogroup B is a major cause of invasive meningococcal disease, but a broadly protective vaccine is not currently licensed. A bivalent recombinant factor ...H-binding protein vaccine (recombinant lipoprotein 2086) has been developed to provide broad coverage against diverse invasive meningococcus serogroup B strains. Our aim was to test the immune response of this vaccine. Methods This randomised, placebo-controlled trial enrolled healthy adolescents from 25 sites in Australia, Poland, and Spain. Exclusion criteria were previous invasive meningococcal disease or serogroup B vaccination, previous adverse reaction or known hypersensitivity to the vaccine, any significant comorbidities, and immunosuppressive therapy or receipt of blood products in the past 6 months. Participants were randomly assigned with a computerised block randomisation scheme to receive ascending doses of vaccine (60, 120, or 200 μg) or placebo at 0, 2, and 6 months. Principal investigators, participants and their guardians, and laboratory personnel were masked to the allocation; dispensing staff were not. Immunogenicity was measured by serum bactericidal assays using human complement (hSBA) against eight diverse meningococcus serogroup B strains. The co-primary endpoints were seroconversion for the two indicator strains (PMB1745 and PMB17) analysed by the Clopper-Pearson method. Local and systemic reactions and adverse events were recorded. The study is registered at ClinicalTrials.gov , number NCT00808028. Findings 539 participants were enrolled and 511 received all three study vaccinations—116 in the placebo group, 21 in the 60 μg group, 191 in the 120 μg group, and 183 in the 200 μg group. The proportion of participants responding with an hSBA titre equal to or greater than the lower limit of quantitation of the hSBA assays (reciprcocal titres of 7 to 18, depending on test strain) was similar for the two largest doses and ranged from 75·6 to 100·0% for the 120 μg dose and 67·9 to 99·0% for the 200 μg dose. Seroconversion for the PMB1745 reference strain was 17 of 19 (89·5%) participants for the 60 μg dose, 103 of 111 (92·8%) participants for the 120 μg dose, 94 of 100 (94·0%) participants for the 200 μg dose, and four of 73 (5·5%) participants for placebo. For the PMB17 reference strain seroconversion was 17 of 21 (81·0%) participants for the 60 μg dose, 97 of 112 (86·6%) participants for the 120 μg dose, 89 of 105 (84·8%) participants for the 200 μg dose, and one of 79 (1·3%) participants for placebo. The hSBA response was robust as shown by the high proportion of responders at hSBA titres up to 16. Mild-to-moderate injection site pain was the most common local reaction (50 occurrences with the 60 μg dose, 437 with the 120 μg dose, 464 with the 200 μg dose, and 54 with placebo). Systemic events, including fatigue and headache, were generally mild to moderate. Overall, adverse events were reported by 18 participants (81·8%) in the 60 μg group, 77 (38·9%) in the 120 μg group, 92 (47·2%) in the 200 μg group, and 54 (44·6%) in the placebo group. Fevers were rare and generally mild (one in the 60 μg group, 24 in the 120 μg group, 35 in the 200 μg group, and five in the placebo group; range, 0–6·3% after each dose). Incidence and severity of fever did not increase with subsequent vaccine dose within groups. One related serious adverse event that resolved without sequelae occurred after the third dose (200 μg). Interpretation The bivalent recombinant lipoprotein 2086 vaccine is immunogenic and induces robust hSBA activity against diverse invasive meningococcus serogroup B disease strains and the vaccine is well tolerated. Recombinant lipoprotein 2086 vaccine is a promising candidate for broad protection against invasive meningococcus serogroup B disease. Funding Wyeth, Pfizer.
Pathological Wnt pathway activation is a conserved hallmark of colorectal cancer. Wnt-activating mutations can be divided into: i) ligand-independent (LI) alterations in intracellular signal ...transduction proteins (
, β-catenin), causing constitutive pathway activation and ii) ligand-dependent (LD) mutations affecting the synergistic R-Spondin axis (
,
-fusions) acting through amplification of endogenous Wnt signal transmembrane transduction. Our aim was to exploit differential Wnt target gene expression to generate a mutation-agnostic biomarker for LD tumours.
We undertook harmonised multi-omic analysis of discovery (n=684) and validation cohorts (n=578) of colorectal tumours collated from publicly available data and the Stratification in Colorectal Cancer Consortium. We used mutation data to establish molecular ground truth and subdivide lesions into LI/LD tumour subsets. We contrasted transcriptional, methylation, morphological and clinical characteristics between groups.
Wnt disrupting mutations were mutually exclusive. Desmoplastic stromal upregulation of
may compensate for absence of epithelial mutation in a subset of stromal-rich tumours. Key Wnt negative regulator genes were differentially expressed between LD/LI tumours, with targeted hypermethylation of some genes (
,
) occurring even in CIMP-negative LD cancers.
mRNA expression was used as a discriminatory molecular biomarker to distinguish LD/LI tumours (area under the curve >0.93).
Epigenetic suppression of appropriate Wnt negative feedback loops is selectively advantageous in LD tumours and differential
expression in LD/LI lesions can be exploited as a molecular biomarker. Distinguishing between LD/LI tumour types is important; patients with LD tumours retain sensitivity to Wnt ligand inhibition and may be stratified at diagnosis to clinical trials of Porcupine inhibitors.
The highly forbidden
electric octupole transition in
is a potential candidate for a redefinition of the SI second. We present a measurement of the absolute frequency of this optical transition, ...performed using a frequency link to International Atomic Time to provide traceability to the SI second. The
optical frequency standard was operated for 76% of a 25-day period, with the absolute frequency measured to be 642 121 496 772 645.14(26) Hz. The fractional uncertainty of
is comparable to that of the best previously reported measurement, which was made by a direct comparison to local caesium primary frequency standards.
The Predictors of Remission in Depression to Individual and Combined Treatments PReDICT study aimed to identify clinical and biological factors predictive of treatment outcomes in major depressive ...disorder among treatment-naive adults. The authors evaluated the efficacy of cognitive-behavioral therapy (CBT) and two antidepressant medications (escitalopram and duloxetine) in patients with major depression and examined the moderating effect of patients' treatment preferences on outcomes.
Adults aged 18-65 with treatment-naive major depression were randomly assigned with equal likelihood to 12 weeks of treatment with escitalopram (10-20 mg/day), duloxetine (30-60 mg/day), or CBT (16 50-minute sessions). Prior to randomization, patients indicated whether they preferred medication or CBT or had no preference. The primary outcome was change in the 17-item Hamilton Depression Rating Scale (HAM-D), administered by raters blinded to treatment.
A total of 344 patients were randomly assigned, with a mean baseline HAM-D score of 19.8 (SD=3.8). The mean estimated overall decreases in HAM-D score did not significantly differ between treatments (CBT: 10.2, escitalopram: 11.1, duloxetine: 11.2). Last observation carried forward remission rates did not significantly differ between treatments (CBT: 41.9%, escitalopram: 46.7%, duloxetine: 54.7%). Patients matched to their preferred treatment were more likely to complete the trial but not more likely to achieve remission.
Treatment guidelines that recommend either an evidence-based psychotherapy or antidepressant medication for nonpsychotic major depression can be extended to treatment-naive patients. Treatment preferences among patients without prior treatment exposure do not significantly moderate symptomatic outcomes.
There has been increasing concern and scrutiny in the use of mesh for certain pelvic organ prolapse procedures. However, mesh erosion was often associated with sites of suture fixation of the mesh to ...the rectum or vagina. Thus, in response to this finding, we replaced our suture material with absorbable monofilament suture.
The purpose of this study was to compare the rates of mesh-related complications after laparoscopic ventral mesh rectopexy, according to the type of suture used in fixation of mesh.
This was retrospective cohort study.
This study was performed at a high-volume, tertiary care center. It was conducted using a prospective database including patients who underwent laparoscopic ventral mesh rectopexy over a 7-year period.
A total of 495 cases were included; 296 (60%) laparoscopic ventral mesh rectopexies were performed using a nonabsorbable suture compared with 199 (40%) with an absorbable suture in a case-matched analysis. In addition, 151 cases of laparoscopic ventral mesh rectopexy with nonabsorbable were matched based on age, sex, and time of follow-up, with an equal number of patients using absorbable monofilament suture.
Primary outcome was symptomatic mesh erosion after rectopexy. Secondary outcomes included other mesh-related complications and/or reoperations.
The erosion rate was 2% (6/495) in the nonabsorbable suture group, including 4 erosions into the rectum and 2 into the vagina. There was no erosion in the group with absorbable suture. This difference was maintained after matching: after a median follow-up of 6 (12) months, there was no erosion in the absorbable suture group versus 3.3% erosion (n = 5) in the nonabsorbable suture group (p = 0.03).
This study was limited by its retrospective design.
Mesh-related complications are reduced using absorbable sutures compared with nonabsorbable sutures when performing laparoscopic ventral mesh rectopexy with synthetic mesh without an increase in rectopexy failures. See Video Abstract at http://links.lww.com/DCR/B49. IMPACTO DEL TIPO DE SUTURA EN LA TASA DE EROSIóN DESPUéS DE LA RECTOPEXIA VENTRAL LAPAROSCóPICA CON MALLA: UN ESTUDIO DE CASOS EMPAREJADOS: Ha habido una creciente preocupación y escrutinio en el uso de la malla para ciertos procedimientos de prolapso de órganos pélvicos. Sin embargo, la erosión de la malla a menudo se asoció con sitios de fijación de sutura de la malla al recto o la vagina. Por lo tanto, en respuesta a este hallazgo, reemplazamos nuestro material de sutura con sutura de monofilamento absorbible.Comparar las tasas de complicaciones relacionadas con la malla después de la rectopexia laparoscópica de malla ventral, de acuerdo al tipo de sutura utilizada en la fijación de la malla.Este fue un estudio de cohorte retrospectivo.Este estudio se realizó en un centro de atención de tercer nivel de alto volumen. Se realizó utilizando una base de datos prospectiva que incluía pacientes que se sometieron a una rectopexia de malla ventral laparoscópica durante un período de 7 años.Se incluyeron un total de 495 casos; 296 (60%) rectopexias de malla ventral laparoscópica utilizando una sutura no reabsorbible en comparación con 199 (40%) con una sutura absorbible en un análisis de casos emparejados. Además, 151 casos de rectopexia ventral laparoscópica con malla no absorbible se emparejaron según la edad, el sexo y el tiempo de seguimiento con un número igual de pacientes que usaban sutura de monofilamento absorbible.La medida de resultado primaria fue la erosión sintomática de la malla después de la rectopexia. La medida de resultado secundarias incluyeron otras complicaciones y/o reoperaciones relacionadas con la malla.La tasa de erosión fue del 2% (6/495) en el grupo de sutura no absorbible; 4 erosiones en el recto y 2 en la vagina. No hubo erosión en el grupo con sutura absorbible. Esta diferencia se mantuvo después del emparejamiento: después de una mediana de seguimiento de 6 (12) meses, no hubo erosión en el grupo de sutura absorbible versus 3.3% de erosión (n = 5) en el grupo de sutura no absorbible (p = 0.03).Este estudio estuvo limitado por su diseño retrospectivo.Las complicaciones relacionadas con la malla se reducen utilizando suturas absorbibles en comparación con las suturas no absorbibles cuando se realiza la rectopexia de malla ventral laparoscópica con malla sintética, sin un aumento en los fracasos de rectopexia. Vea el Resumen del Video en http://links.lww.com/DCR/B49.
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