Symptom Signatures and Diagnostic Timeliness in Cancer Patients: A Review of Current Evidence

Early diagnosis is an important aspect of contemporary cancer prevention and control strategies, as the majority of patients are diagnosed following symptomatic presentation. The nature of presenting symptoms can critically influence the length of the diagnostic intervals from symptom onset to presentation (the patient interval), and from first presentation to specialist referral (the primary care interval). Understanding which symptoms are associated with longer diagnostic intervals to help the targeting of early diagnosis initiatives is an area of emerging research. In this Review, we consider the methodological challenges in studying the presenting symptoms and intervals to diagnosis of cancer patients, and summarize current evidence on presenting symptoms associated with a range of common and rarer cancer sites. We propose a taxonomy of cancer sites considering their symptom signature and the predictive value of common presenting symptoms. Finally, we consider evidence on associations between symptomatic presentations and intervals to diagnosis before discussing implications for the design, implementation, and evaluation of public health or health system interventions to achieve the earlier detection of cancer

The effect of food type on the portion size effect in children aged 2-12 years: A systematic review and meta-analysis.

Visual cues such as plate size, amount of food served and packaging are known to influence the effects of portion size on food intake. Unit bias is a well characterised heuristic and helps to determine consumption norms. In an obesogenic environment where large portions are common place, the unit or segmentation bias may be overridden promoting overconsumption of both amorphous or unit foods. The aim of this review was to investigate the impact of offering unit or amorphous food on the portion size effect (PSE) in children aged 2–12 years. A systematic search for literature was conducted in Medline, PsycInfo and Web of Science in February 2018. A total of 1197 papers were retrieved following the searches. Twenty-one papers were included in the systematic review, of which 15 provided requisite statistical information for inclusion in a random effects meta-analysis. Increasing children's food portion size by 51–100% led to a significant increase in intake (SMD = 0.47, 95% CI: 0.39–0.55). There was no evidence to suggest that increases in consumption were related to food type (p = 0.33), child age (p = 0.47) or initial portion size served (p=0.14). Residual heterogeneity was not significant (p=0.24). The PSE was demonstrated in children aged 2–12 years when offered both unit and amorphous food items. The effect was not restricted by food type, child age or influenced by initial portion size served. Of the studies included in the meta-analysis between study heterogeneity was low suggesting minimal variation in treatment effects between studies, however, more research is required to understand the mechanisms of the PSE in preschool children. Future research should determine feasible methods to downsize portion sizes served to children

Can we do better? A qualitative study in the East of England investigating patient experience and acceptability of using the faecal immunochemical test in primary care.

OBJECTIVES: The faecal immunochemical test (FIT) is increasingly used in UK primary care to triage patients presenting with symptoms and at different levels of colorectal cancer risk. Evidence is scarce on patients' views of using FIT in this context. We aimed to explore patients' care experience and acceptability of using FIT in primary care. DESIGN: A qualitative semi-structured interview study. Interviews were conducted via Zoom between April and October 2020. Transcribed recordings were analysed using framework analysis. SETTING: East of England general practices. PARTICIPANTS: Consenting patients (aged ≥40 years) who presented in primary care with possible symptoms of colorectal cancer, and for whom a FIT was requested, were recruited to the FIT-East study. Participants were purposively sampled for this qualitative substudy based on age, gender and FIT result. RESULTS: 44 participants were interviewed with a mean age 61 years, and 25 (57%) being men: 8 (18%) received a positive FIT result. Three themes and seven subthemes were identified. Participants' familiarity with similar tests and perceived risk of cancer influenced test experience and acceptability. All participants were happy to do the FIT themselves and to recommend it to others. Most participants reported that the test was straightforward, although some considered it may be a challenge to others. However, test explanation by healthcare professionals was often limited. Furthermore, while some participants received their results quickly, many did not receive them at all with the common assumption that 'no news is good news'. For those with a negative result and persisting symptoms, there was uncertainty about any next steps. CONCLUSIONS: While FIT is acceptable to patients, elements of communication with patients by the healthcare system show potential for improvement. We suggest possible ways to improve the FIT experience, particularly regarding communication about the test and its results

Fabrication technology for ODS Alloy MA957

A successful fabrication schedule has been developed at Carpenter Technology Corporation for the production of MA957 fuel and blanket cladding. Difficulties with gun drilling, plug drawing and recrystallization were overcome to produce a pilot lot of tubing. This report documents the fabrication efforts of two qualified vendors and the support studies performed at WHC to develop the fabrication-schedule

Enhancement of toxin- and virus-neutralizing capacity of single-domain antibody fragments by N-glycosylation

Single-domain antibody fragments (VHHs) have several beneficial properties as compared to conventional antibody fragments. However, their small size complicates their toxin- and virus-neutralizing capacity. We isolated 27 VHHs binding Escherichia coli heat-labile toxin and expressed these in Saccharomyces cerevisiae. The most potent neutralizing VHH (LT109) was N-glycosylated, resulting in a large increase in molecular mass. This suggests that N-glycosylation of LT109 improves its neutralizing capacity. Indeed, deglycosylation of LT109 decreased its neutralizing capacity three- to fivefold. We also studied the effect of glycosylation of two previously isolated VHHs on their ability to neutralize foot-and-mouth disease virus. For this purpose, these VHHs that lacked potential N-glycosylation sites were genetically fused to another VHH that was known to be glycosylated. The resulting fusion proteins were also N-glycosylated. They neutralized the virus at at least fourfold-lower VHH concentrations as compared to the single, non-glycosylated VHHs and at at least 50-fold-lower VHH concentrations as compared to their deglycosylated counterparts. Thus, we have shown that N-glycosylation of VHHs contributes to toxin- and virus-neutralizing capacity

The significance of macrophage phenotype in cancer and biomaterials

Macrophages have long been known to exhibit heterogeneous and plastic phenotypes. They show functional diversity with roles in homeostasis, tissue repair, immunity and disease. There exists a spectrum of macrophage phenotypes with varied effector functions, molecular determinants, cytokine and chemokine profiles, as well as receptor expression. In tumor microenvironments, the subset of macrophages known as tumor-associated macrophages generates byproducts that enhance tumor growth and angiogenesis, making them attractive targets for anti-cancer therapeutics. With respect to wound healing and the foreign body response, there is a necessity for balance between pro-inflammatory, wound healing, and regulatory macrophages in order to achieve successful implantation of a scaffold for tissue engineering. In this review, we discuss the multitude of ways macrophages are known to be important in cancer therapies and implanted biomaterials

Universality of interpersonal psychotherapy (IPT) problem areas in Thai depressed patients

<p>Abstract</p> <p>Background</p> <p>Many studies have shown the efficacy of interpersonal psychotherapy (IPT) on depression; however, there are limited studies concerning the universality of the IPT problem areas in different countries. This study identifies whether the interpersonal problem areas defined in the IPT manual are endorsed by Thai depressed patients.</p> <p>Methods</p> <p>The Thai Hamilton Rating Scale for Depression (Thai HRSD) and Thai Interpersonal Questionnaire were used to assess 90 depressed and 90 non-depressed subjects in King Chulalongkorn Memorial Hospital, during July 2007 - January 2008. The association between interpersonal problem areas/sociodemographic variables and depressive disorder were analyzed by chi-square test. A multivariable analysis was performed by using logistic regression to identify the remaining factors associated with depressive disorder.</p> <p>Results</p> <p>Most of the subjects were young to middle-aged females living in Bangkok and the Central Provinces. All four interpersonal problem areas (grief, interpersonal role disputes, role transitions, and interpersonal deficits) were increased in the depressed subjects as compared to the non-depressed subjects, as were the sociodemographic variables (low education, unemployment, low income, and having a physical illness). Logistic regression showed that all interpersonal problem areas still remained problems associated with depression (grief: adjusted OR = 6.01, 95%CI = 1.93 - 18.69, p < 0.01; interpersonal role disputes: adjusted OR = 6.01, 95%CI = 2.18 - 16.52, p < 0.01; role transitions: adjusted OR = 26.30, 95%CI = 7.84 - 88.25, p < 0.01; and interpersonal deficits: adjusted OR = 2.92, 95%CI = 1.12 - 7.60, p < 0.05).</p> <p>Conclusion</p> <p>All four interpersonal problem areas were applicable to Thai depressed patients.</p

Mouse allergen, lung function, and atopy in Puerto Rican children

Objective: To examine the relation between mouse allergen exposure and asthma in Puerto Rican children. Methods: Mus m 1, Der p 1, Bla g 2, and Fel d 1 allergens were measured in dust samples from homes of Puerto Rican children with (cases) and without (controls) asthma in Hartford, CT (n = 449) and San Juan (SJ), Puerto Rico (n = 678). Linear or logistic regression was used for the multivariate analysis of mouse allergen (Mus m 1) and lung function (FEV1 and FEV1/FVC) and allergy (total IgE and skin test reactivity (STR) to ≥1 allergen) measures. Results: Homes in SJ had lower mouse allergen levels than those in Hartford. In multivariate analyses, mouse allergen was associated with higher FEV1 in cases in Hartford (+70.6 ml, 95% confidence interval (CI) = 8.6-132.7 ml, P = 0.03) and SJ (+45.1 ml, 95% CI = -0.5 to 90.6 ml, P = 0.05). In multivariate analyses of controls, mouse allergen was inversely associated with STR to ≥1 allergen in non-sensitized children (odds ratio [OR] for each log-unit increment in Mus m 1 = 0.7, 95% CI = 0.5-0.9, P<0.01). In a multivariate analysis including all children at both study sites, each log-increment in mouse allergen was positively associated with FEV1 (+28.3 ml, 95% CI = 1.4-55.2 ml, P = 0.04) and inversely associated with STR to ≥1 allergen (OR for each log-unit increment in Mus m 1 = 0.8, 95% CI = 0.6-0.9, P<0.01). Conclusions: Mouse allergen is associated with a higher FEV1 and lower odds of STR to ≥1 allergen in Puerto Rican children. This may be explained by the allergen itself or correlated microbial exposures. © 2012 Forno et al

RASSF1A–LATS1 signalling stabilizes replication forks by restricting CDK2-mediated phosphorylation of BRCA2

Genomic instability is a key hallmark of cancer leading to tumour heterogeneity and therapeutic resistance. ​BRCA2 has a fundamental role in error-free DNA repair but also sustains genome integrity by promoting ​RAD51 nucleofilament formation at stalled replication forks. ​CDK2 phosphorylates ​BRCA2 (pS3291-​BRCA2) to limit stabilizing contacts with polymerized ​RAD51; however, how replication stress modulates ​CDK2 activity and whether loss of pS3291-​BRCA2 regulation results in genomic instability of tumours are not known. Here we demonstrate that the Hippo pathway kinase ​LATS1 interacts with ​CDK2 in response to genotoxic stress to constrain pS3291-​BRCA2 and support ​RAD51 nucleofilaments, thereby maintaining genomic fidelity during replication stalling. We also show that ​LATS1 forms part of an ​ATR-mediated response to replication stress that requires the tumour suppressor ​RASSF1A. Importantly, perturbation of the ​ATR–​RASSF1A–​LATS1 signalling axis leads to genomic defects associated with loss of ​BRCA2 function and contributes to genomic instability and ‘BRCA-ness’ in lung cancers

Expression of a barley cystatin gene in maize enhances resistance against phytophagous mites by altering their cysteine-proteases

Phytocystatins are inhibitors of cysteine-proteases from plants putatively involved in plant defence based on their capability of inhibit heterologous enzymes. We have previously characterised the whole cystatin gene family members from barley (HvCPI-1 to HvCPI-13). The aim of this study was to assess the effects of barley cystatins on two phytophagous spider mites, Tetranychus urticae and Brevipalpus chilensis. The determination of proteolytic activity profile in both mite species showed the presence of the cysteine-proteases, putative targets of cystatins, among other enzymatic activities. All barley cystatins, except HvCPI-1 and HvCPI-7, inhibited in vitro mite cathepsin L- and/or cathepsin B-like activities, HvCPI-6 being the strongest inhibitor for both mite species. Transgenic maize plants expressing HvCPI-6 protein were generated and the functional integrity of the cystatin transgene was confirmed by in vitro inhibitory effect observed against T. urticae and B. chilensis protein extracts. Feeding experiments impaired on transgenic lines performed with T. urticae impaired mite development and reproductive performance. Besides, a significant reduction of cathepsin L-like and/or cathepsin B-like activities was observed when the spider mite fed on maize plants expressing HvCPI-6 cystatin. These findings reveal the potential of barley cystatins as acaricide proteins to protect plants against two important mite pests