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In the UK, the National Institute for Health and Care Excellence (NICE) recommends that women at moderate or high risk of breast cancer be offered risk-reducing medication and enhanced breast screening/surveillance. In June 2022, NICE withdrew a statement recommending assessment of risk in primary care only when women present with concerns. This shift to the proactive assessment of risk substantially changes the role of primary care, in effect paving the way for a primary care-based screening programme to identify those at moderate or high risk of breast cancer. In this article, we review the literature surrounding proactive breast cancer risk assessment within primary care against the consolidated framework for screening. We find that risk assessment for women under 50 years currently satisfies many of the standard principles for screening. Most notably, there are large numbers of women at moderate or high risk currently unidentified, risk models exist that can identify those women with reasonable accuracy, and management options offer the opportunity to reduce breast cancer incidence and mortality in that group. However, there remain a number of uncertainties and research gaps, particularly around the programme/system requirements, that need to be addressed before these benefits can be realised. [ABSTRACT FROM AUTHOR]

With more than 20 Food and Drug Administration (FDA)-approved poly (ethylene glycol) (PEG) modified drugs on the market, PEG is the gold standard polymer in bioconjugation. The coupling improves stability, efficiency and can prolong blood circulation time of therapeutic proteins. Even though PEGylation is described as non-toxic and non-immunogenic, reports accumulate with data showing allergic reactions to PEG. Since PEG is not only applied in therapeutics, but can also be found in foods and cosmetics, anti-PEG-antibodies can occur even without a medical treatment. Hypersensitivity to PEG thereby can lead to a reduced drug efficiency, fast blood clearance and in rare cases anaphylactic reactions. Therefore, finding alternatives for PEG is crucial. In this study, we present linear polyglycerol (LPG) for bioconjugation as an alternative polymer to PEG. We report the conjugation of LPG and PEG by click-chemistry to the glycoprotein erythropoietin (EPO), synthesized in a eukaryotic cell-free protein synthesis system. Furthermore, the influence of the polymers on EPOs stability and activity on a growth hormone dependent cell-line was evaluated. The similar characteristics of both bioconjugates show that LPGylation can be a promising alternative to PEGylation. [ABSTRACT FROM AUTHOR]

Sugarcane is one of the most promising biomass resources in the developing bioeconomy. It is a source of fermentable sugars and of lignocellulosic biomass that can be converted to a variety of products. Brazil is the leading producer of sugarcane, with 734 million tons projected for 2022 and a yield of 74 tons per hectare. Sugarcane is already an important source of sugar, ethanol, and electricity through the direct burning of sugarcane bagasse, but its potential goes far beyond these products. For being easily fermentable, sugarcane juice is a promising source for other bio-based products, and the valorization of sugarcane residues in existing biorefineries has enormous potential, from the production of biogas from vinasse to the valorization of CO2, recovery of xylans and xylooligosaccharides, production of hydrogels, biosorbents, and 3G bioproducts. This manuscript will address the impact of sugarcane in the Brazilian bioeconomy, the status of technological development in sugarcane biorefineries, and the perspectives for sugarcane and its residues in a circular bioeconomy. [ABSTRACT FROM AUTHOR]

Background: Pilocytic astrocytoma is the most frequent pediatric glioma. Despite its overall good prognosis, complete surgical resection is sometimes unfeasible, especially for patients with deep-seated tumors. For these patients, the identification of targetable genetic alterations such as NTRK fusions, raised as a new hope for therapy. The presence of gene fusions involving NTRK2 has been rarely reported in pilocytic astrocytoma. The aim of the present study was to investigate the frequency of NTRK2 alterations in a series of Brazilian pilocytic astrocytomas. Methods: Sixty-nine pilocytic astrocytomas, previously characterized for BRAF and FGFR1 alterations were evaluated. The analysis of NTRK2 alterations was performed using a dual color break apart fluorescence in situ hybridization (FISH) assay. Results: NTRK2 fusions were successfully evaluated by FISH in 62 of the 69 cases. Neither evidence of NTRK2 gene rearrangements nor NTRK2 copy number alterations were found. Conclusions: NTRK2 alterations are uncommon genetic events in pilocytic astrocytomas, regardless of patients' clinicopathological and molecular features. [ABSTRACT FROM AUTHOR]

Physical stress is common in GI endoscopists, leading to musculoskeletal disorders. Considering the increasing complexity of interventional GI endoscopy with prolonged examination time, work-related musculoskeletal disorders have come into focus. However, data on work-related health stress in German endoscopists are elusive. The aim of this study was therefore to investigate the prevalence and consequences of work-related musculoskeletal disorders in German endoscopists. A 24-item questionnaire on endoscopy-associated musculoskeletal disorders and standardized pain assessment was developed by an interdisciplinary team of endoscopists and sports medics. The survey was distributed online by the leading German societies for gastroenterology and endoscopy. Overall, 151 German practicing endoscopists took part in the study. Regarding the average number of endoscopic procedures per week, the study collective consisted mainly of high-volume endoscopists. The survey showed that most participants suffered from general musculoskeletal disorders (82.8%) and from work-related musculoskeletal disorders (76.8%). The most affected body parts were the neck, low back, thumb, and shoulder. Temporary absence from work due to symptoms was reported by 9.9% of the respondents. Over 30% of participating endoscopists stated the need for analgesics or physiotherapy due to musculoskeletal disorders. Age, professional experience and work time were identified as relevant risk factors for musculoskeletal health issues. A high number of German endoscopists are affected by musculoskeletal disorders due to specific working postures and repetitive movements with a large impact on personal health. Further interventional studies are mandatory to improve the risk prevention of endoscopic activity. [ABSTRACT FROM AUTHOR]

Introduction: Lower gastrointestinal (GI) cancers are a major cause of cancer deaths worldwide. Prognosis improves with earlier diagnosis, and non-invasive biomarkers have the potential to aid with early detection. Substantial investment has been made into the development of biomarkers; however, studies are often carried out in specialist settings and few have been evaluated for low-prevalence populations.Methods: We aimed to identify novel biomarkers for the detection of lower GI cancers that have the potential to be evaluated for use in primary care. MEDLINE, Embase, Emcare and Web of Science were systematically searched for studies published in English from January 2000 to October 2019. Reference lists of included studies were also assessed. Studies had to report on measures of diagnostic performance for biomarkers (single or in panels) used to detect colorectal or anal cancers. We included all designs and excluded studies with fewer than 50 cases/controls. Data were extracted from published studies on types of biomarkers, populations and outcomes. Narrative synthesis was used, and measures of specificity and sensitivity were meta-analysed where possible.Results: We identified 142 studies reporting on biomarkers for lower GI cancers, for 24,844 cases and 45,374 controls. A total of 378 unique biomarkers were identified. Heterogeneity of study design, population type and sample source precluded meta-analysis for all markers except methylated septin 9 (mSEPT9) and pyruvate kinase type tumour M2 (TuM2-PK). The estimated sensitivity and specificity of mSEPT9 was 80.6% (95% CI 76.6-84.0%) and 88.0% (95% CI 79.1-93.4%) respectively; TuM2-PK had an estimated sensitivity of 81.6% (95% CI 75.2-86.6%) and specificity of 80.1% (95% CI 76.7-83.0%).Conclusion: Two novel biomarkers (mSEPT9 and TuM2-PK) were identified from the literature with potential for use in lower-prevalence populations. Further research is needed to validate these biomarkers in primary care for screening and assessment of symptomatic patients. [ABSTRACT FROM AUTHOR]

Colorectal cancer (CRC) is the third most common cancer worldwide. Primary care professionals can play an important role in both prevention and early detection of CRC. Most CRCs are attributed to modifiable lifestyle factors, which can be addressed within primary care, and promotion of population-based screening programmes can aid early cancer detection in asymptomatic patients. Primary care professionals have a vital role in clinically assessing patients presenting with symptoms that may indicate cancer, as most patients with CRC first present with symptoms. These assessments are often challenging-many of the symptoms of CRC are non-specific and commonly occur in patients presenting with non-malignant disease. The range of options for investigating symptomatic patients in primary care is rapidly growing. Simple tests, such as faecal immunochemical testing (FIT), are now being used to guide decisions around referral for more invasive tests, such as colonoscopy, while direct access to specialist investigations is also becoming more common. Clinical decision support tools (CDSTs) which calculate cancer risk based on symptomatology, patient characteristics and test results can provide an additional resource to guide decisions on further investigation. This article explores the challenges of CRC prevention and detection from the primary care perspective, discusses current evidence-based approaches for CRC detection used in primary care (with examples from UK guidelines), and highlights emerging research which may likely alter practice in the future. [ABSTRACT FROM AUTHOR]

Background: The faecal immunochemical test (FIT) was introduced to triage patients with low-risk symptoms of possible colorectal cancer in English primary care in 2017, underpinned by little primary care evidence.Methods: All healthcare providers in the South West of England (population 4 million) participated in this evaluation. 3890 patients aged ≥50 years presenting in primary care with low-risk symptoms of colorectal cancer had a FIT from 01/06/2018 to 31/12/2018. A threshold of 10 μg Hb/g faeces defined a positive test.Results: Six hundred and eighteen (15.9%) patients tested positive; 458 (74.1%) had an urgent referral to specialist lower gastrointestinal (GI) services within three months. Forty-three were diagnosed with colorectal cancer within 12 months. 3272 tested negative; 324 (9.9%) had an urgent referral within three months. Eight were diagnosed with colorectal cancer within 12 months. Positive predictive value was 7.0% (95% CI 5.1-9.3%). Negative predictive value was 99.8% (CI 99.5-99.9%). Sensitivity was 84.3% (CI 71.4-93.0%), specificity 85.0% (CI 83.8-86.1%). The area under the ROC curve was 0.92 (CI 0.86-0.96). A threshold of 37 μg Hb/g faeces would identify patients with an individual 3% risk of cancer.Conclusions: FIT performs exceptionally well to triage patients with low-risk symptoms of colorectal cancer in primary care; a higher threshold may be appropriate in the wake of the COVID-19 crisis. [ABSTRACT FROM AUTHOR]

Introduction: Detecting upper gastrointestinal (GI) cancers in primary care is challenging, as cancer symptoms are common, often non-specific, and most patients presenting with these symptoms will not have cancer. Substantial investment has been made to develop biomarkers for cancer detection, but few have reached routine clinical practice. We aimed to identify novel biomarkers for upper GI cancers which have been sufficiently validated to be ready for evaluation in low-prevalence populations. Methods: We systematically searched MEDLINE, Embase, Emcare, and Web of Science for studies published in English from January 2000 to October 2019 (PROSPERO registration CRD42020165005). Reference lists of included studies were assessed. Studies had to report on second measures of diagnostic performance (beyond discovery phase) for biomarkers (single or in panels) used to detect pancreatic, oesophageal, gastric, and biliary tract cancers. We included all designs and excluded studies with less than 50 cases/controls. Data were extracted on types of biomarkers, populations and outcomes. Heterogeneity prevented pooling of outcomes. Results: We identified 149 eligible studies, involving 22,264 cancer cases and 49,474 controls. A total of 431 biomarkers were identified (183 microRNAs and other RNAs, 79 autoantibodies and other immunological markers, 119 other proteins, 36 metabolic markers, 6 circulating tumour DNA and 8 other). Over half (n = 231) were reported in pancreatic cancer studies. Only 35 biomarkers had been investigated in at least two studies, with reported outcomes for that individual marker for the same tumour type. Apolipoproteins (apoAII-AT and apoAII-ATQ), and pepsinogens (PGI and PGII) were the most promising biomarkers for pancreatic and gastric cancer, respectively. Conclusion: Most novel biomarkers for the early detection of upper GI cancers are still at an early stage of matureness. Further evidence is needed on biomarker performance in low-prevalence populations, in addition to implementation and health economic studies, before extensive adoption into clinical practice can be recommended. [ABSTRACT FROM AUTHOR]

Turfs are among the major benthic components of reef systems worldwide. The nearly complete genome sequences, basic physiological characteristics, and phylogenomic reconstruction of two phycobiliprotein-rich filamentous cyanobacteria strains isolated from turf assemblages from the Abrolhos Bank (Brazil) are investigated. Both Adonisia turfae CCMR0081T (= CBAS 745T) and CCMR0082 contain approximately 8 Mbp in genome size and experiments identified that both strains exhibit chromatic acclimation. Whereas CCMR0081T exhibits chromatic acclimation type 3 (CA3) regulating both phycocyanin (PC) and phycoerythrin (PE), CCMR0082 strain exhibits chromatic acclimation type 2 (CA2), in correspondence with genes encoding specific photosensors and regulators for PC and PE. Furthermore, a high number and diversity of secondary metabolite synthesis gene clusters were identified in both genomes, and they were able to grow at high temperatures (28 °C, with scant growth at 30 °C). These characteristics provide insights into their widespread distribution in reef systems. [ABSTRACT FROM AUTHOR]

Pharmacogenomics describes interpatient genetic variability in drug responses. Information based on whole genome sequencing will soon open up the field of pharmacogenomics and facilitate the use of genomic information relating to drug metabolism and drug responses. We undertook a qualitative study, aiming to explore the potential barriers, opportunities and challenges facing the implementation of pharmacogenomics into primary care. Semi-structured interviews were undertaken with 18 clinical participants (16 GPs and 2 other clinicians). All interviews were recorded and transcribed verbatim. Using a thematic analysis approach, data items were coded, ordered and themes constructed. Most participants were aged 55–60 years and worked as part-time clinical GPs with other clearly defined roles. The emerging themes covered several areas of concern, including the following: the utility of pharmacogenomics and the value of introducing such testing into primary care; how to educate the primary care workforce and 'mainstream' pharmacogenomics; the ethical, legal and social aspects of pharmacogenomics and its impact on patients; and potential impacts on the healthcare system particularly around economics and informatics. Most participants had concerns about pharmacogenomics and felt that there were a number of barriers and challenges to its implementation into routine primary care. Most striking were their concerns around the cost-effectiveness of using pharmacogenomics in primary care. At the same time most recognised the increasing availability of direct-to-consumer testing, and felt that this would drive the need to understand the ethical and social implications of using genomic information in primary care. This study has raised important issues that need to be considered when planning the implementation of pharmacogenomics into clinical practice. Prior to the implementation of genomic testing into day-to-day practice in UK primary care, it is important that considerations around education, cost-effectiveness and informatics are addressed, as well as the impact on patients. [ABSTRACT FROM AUTHOR]

An amendment to this paper has been published and can be accessed via a link at the top of the paper. [ABSTRACT FROM AUTHOR]

The Clean Air Act's National Ambient Air Quality Standards (NAAQS) and New Source Review (NSR) permitting work in conjunction to improve ambient air quality in the United States. However, all previous studies of the NAAQS ignore this joint nature and focus solely on the effects of NAAQS non-attainment designation on various economic outcomes. Additionally, previous studies ignore the potentiality of regulatory spillover, i.e., abatement for one pollutant decreasing emissions of other, non-regulated pollutants, from the NAAQS. In this paper, we first examine the actions of plant managers who face varying degrees of regulatory oversight. We then estimate the differential effects of the NAAQS and NSR on emissions at coal-fired power plants, while also examining spillover effects. Collectively, this study adds to the literature on environmental regulation in two key ways. First, we use comprehensive data on facility-level NSR permit receipt to examine the differential effects of the NAAQS on plants regulated jointly by NSR and NAAQS non-attainment and those plants regulated only by NAAQS non-attainment. We investigate how the monitoring of areas with non-attainment designation leads to the avoidance of regulatory scrutiny by local plants and find that regulated facilities not subjected to the technological requirements of NSR decreased NO x emissions by 20%. We also examine the mechanisms through which this abatement occurs, e.g., technology, use of cleaner inputs. Second, we identify the spillover effects of the NAAQS for certain pollutants by examining the effects of disparate non-attainment designations from the emissions in question. We find a significant decrease in NO x and CO 2 emissions as a result of carbon monoxide and SO 2 -affected non-attainment designation, respectively. We provide evidence that regulatory spillover in this case is the result of different emission control strategies. [ABSTRACT FROM AUTHOR]

Skin cancer, including melanoma, basal cell carcinoma and cutaneous squamous cell carcinoma, has one of the highest global incidences of any form of cancer. In 2016 more than 16,000 people were diagnosed with melanoma in the UK. Over the last decade the incidence of melanoma has increased by 50% in the UK, and about one in ten melanomas are diagnosed at a late stage. Among the keratinocyte carcinomas (previously known as non-melanoma skin cancers), basal cell carcinoma is the most common cancer amongst Caucasian populations. The main risk factor for all skin cancer is exposure to ultraviolet radiation-more than 80% are considered preventable. Primary care clinicians have a vital role to play in detecting and managing patients with skin lesions suspected to be skin cancer, as timely diagnosis and treatment can improve patient outcomes, particularly for melanoma. However, detecting skin cancer can be challenging, as common non-malignant skin lesions such as seborrhoeic keratoses share features with less common skin cancers. Given that more than 80% of skin cancers are attributed to ultraviolet (UV) exposure, primary care clinicians can also play an important role in skin cancer prevention. This article is one of a series discussing cancer prevention and detection in primary care. Here we focus on the most common types of skin cancer: melanoma, squamous cell carcinoma and basal cell carcinoma. We describe the main risk factors and prevention advice. We summarise key guidance on the symptoms and signs of skin cancers and their management, including their initial assessment and referral. In addition, we review emerging technologies and diagnostic aids which may become available for use in primary care in the near future, to aid the triage of suspicious skin lesions. [ABSTRACT FROM AUTHOR]

We report here the novel species to encompass the isolate A649T (=CBAS 716T = CBRVS P1061T) obtained from viscera of the healthy pufferfish Sphoeroides spengleri (Family Tetraodontidae). Genomic taxonomy analysis demonstrates that the novel strain A649T had < 95% average amino acid identity/average nucleotide identity (AAI/ANI) and < 70% similarity of genome-to-genome distance (GGDH) towards its closest neighbors which places A649T into a new Enterovibrio species (Enterovibrio baiacu sp nov.). In silico phenotyping disclosed several features that may be used to differentiate related Enterovibrio species. The nearly complete genome assembly of strain A649T consisted of 5.4 Mbp and 4826 coding genes. [ABSTRACT FROM AUTHOR]

Bladder and kidney cancer are the 10th and 7th most common cancers in the United Kingdom (UK). They present with symptoms that are typically investigated via the same diagnostic pathway. However, diagnosing these cancers can be challenging, especially for kidney cancer, as many of the symptoms are non-specific and occur commonly in patients without cancer. Furthermore, the recognition and evaluation of these symptoms may differ because of the lack of supporting high-quality evidence to inform management, a problem also reflected in currently ambiguous guidelines. The majority of these two cancers are diagnosed following a referral from a general practitioner. In this article, we summarise current UK and United States (US) guidelines for investigating common symptoms of bladder and kidney cancer-visible haematuria, non-visible haematuria and urinary tract infections. Our article aims to support clinicians in recognising and investigating patients with symptoms of possible bladder and kidney cancer in a timely fashion. We discuss challenges during the diagnostic process and possible future interventions for improvement. [ABSTRACT FROM AUTHOR]

Purpose: Allergic rhinitis (AR) is a common risk factor for sleep disordered breathing (SDB) in children. Allergy to pollen is a trigger for allergic rhinitis, causing nasal inflammation, upper airway congestion and obstruction. We aimed to determine if the pollen count on the day of diagnostic polysomnography for SDB affected the result. Methods: Children (3–18 years; n = 90) who participated in research studies between 1 October and 31 December, when daily regional pollen counts were available, in the years 2005–2016 were eligible for inclusion. All children underwent overnight polysomnography for assessment of SDB severity. Pollen was categorised as grass or other pollen. Multiple stepwise linear regression was performed to determine whether the pollen count for that day, a diagnosis of asthma, age, and BMI-z-score were determinants of respiratory parameters measured on polysomnography, including the obstructive apnoea hypopnoea index (OAHI), SpO2 nadir, average SpO2 drop, SpO2 < 90%, oxygen desaturation index > 4% (ODI4), and average transcutaneous CO2 (TCM). Results: Sixteen/90 children had AR. In children with AR, an increase in grass pollen of 1 grain/m3 predicted an increase in OAHI of 0.2 events/h, ODI4 of 0.18 times/h, SpO2 < 90% of 0.03 times/h, and TCM of 0.07 mmHg. None of the factors were determinants of SDB severity in children without AR. Conclusion: Our findings highlight that daily pollen counts may be an important factor influencing the severity of SDB on a single night of polysomnography in children with clinical allergic rhinitis and should be taken into account when determining treatment options. [ABSTRACT FROM AUTHOR]

Mutations in the retinoblastoma (RB) tumour suppressor pathway are a hallmark of cancer and a prevalent feature of lung adenocarcinoma1–3. Although RB was the first tumour suppressor to be identified, the molecular and cellular basis that underlies selection for persistent RB loss in cancer remains unclear4–6. Methods that reactivate the RB pathway using inhibitors of cyclin-dependent kinases CDK4 and CDK6 are effective in some cancer types and are currently under evaluation for the treatment of lung adenocarcinoma7–9. Whether RB pathway reactivation will have therapeutic effects and whether targeting CDK4 and CDK6 is sufficient to reactivate RB pathway activity in lung cancer remains unknown. Here we model RB loss during lung adenocarcinoma progression and pathway reactivation in established oncogenic KRAS-driven tumours in mice. We show that RB loss enables cancer cells to bypass two distinct barriers during tumour progression. First, RB loss abrogates the requirement for amplification of the MAPK signal during malignant progression. We identify CDK2-dependent phosphorylation of RB as an effector of MAPK signalling and critical mediator of resistance to inhibition of CDK4 and CDK6. Second, RB inactivation deregulates the expression of cell-state-determining factors, facilitates lineage infidelity and accelerates the acquisition of metastatic competency. By contrast, reactivation of RB reprograms advanced tumours towards a less metastatic cell state, but is nevertheless unable to halt cancer cell proliferation and tumour growth due to adaptive rewiring of MAPK pathway signalling, which restores a CDK-dependent suppression of RB. Our study demonstrates the power of reversible gene perturbation approaches to identify molecular mechanisms of tumour progression, causal relationships between genes and the tumour suppressive programs that they control and critical determinants of successful cancer therapy. Loss of RB promotes both malignant progression and the development of metastatic disease; however, whereas reactivation of the RB pathway can revert metastatic tumour cell states to non-metastatic cell states, malignant cell proliferation is supported by MAPK–CDK2-dependent suppression of RB. [ABSTRACT FROM AUTHOR]

Microalgae diversity is constantly being studied and explored for biotechnological uses. The shallow lake system of Lençois Maranhenses (SLLM) is a unique coastal ecosystem in northeast Brazil found interspersed in a field of sand dunes. Organisms in these tropical lakes are constantly exposed to high temperatures and solar irradiance. Yet, little is known about the diversity of culturable microalgae in this aquatic ecosystem. This study reports the use of flow cytometry with fluorescence-activated cell sorting (FACS) to isolate single microalgae cells/coenobia from five lakes in SLLM, accessing the efficiency of this isolation technique with two types of culture media. To retrieve the highest diversity of culturable microalgae, planktonic, benthic, and epiphytic samples were collected and processed by FACS. The diversity of microalgae in natural lake communities was described by morphology-based taxonomy. Isolates of the most abundant phylum established in cultures (Chlorophyta) were characterized by gene sequencing (18S rDNA). A total of 3072 microalgal cells/coenobia were sorted into 96-well plates. From these, 945 wells presented algal growth (31% success rate). Based on morphological diversity and adaptability to culture conditions, a set of 171 strains were selected to be incorporated in a culture collection. Microalgae present in the lakes belonged to six phyla, with four of them represented in the cultured strains. Our sampling strategy coupled with FACS isolation retrieved a fairly large number and diversity of microalgal strains with minimum isolation effort from a unique coastal environment. The monoclonal cultures established in this study offer new opportunities for basic and applied research on microalgae biotechnology.ᅟ [ABSTRACT FROM AUTHOR]

Using an optimal control approach, I examine the effectiveness of various strategies for firms to investing in clean technology when faced with an emissions tax in a duopolistic market. Explicitly allowing for the cumulative nature of R&D, I show that emissions per unit of output are lowest when the firms cooperate in R&D, as compared to the scenarios when they compete in R&D or merge into a single entity. It is shown that R&D cooperation leads to the highest level of social welfare among the three alternative scenarios, and that a profit maximizing firm will never choose the most environmentally conscience investment strategy. In contrast to the traditional static analysis, which ignores the temporal effects associated with R&D, my dynamic analysis has implications for emission tax policy and environmental innovation to improve overall welfare. [ABSTRACT FROM AUTHOR]

Background: This study aimed to compare and externally validate risk scores developed to predict incident colorectal cancer (CRC) that include variables routinely available or easily obtainable via self-completed questionnaire.Methods: External validation of fourteen risk models from a previous systematic review in 373 112 men and women within the UK Biobank cohort with 5-year follow-up, no prior history of CRC and data for incidence of CRC through linkage to national cancer registries.Results: There were 1719 (0.46%) cases of incident CRC. The performance of the risk models varied substantially. In men, the QCancer10 model and models by Tao, Driver and Ma all had an area under the receiver operating characteristic curve (AUC) between 0.67 and 0.70. Discrimination was lower in women: the QCancer10, Wells, Tao, Guesmi and Ma models were the best performing with AUCs between 0.63 and 0.66. Assessment of calibration was possible for six models in men and women. All would require country-specific recalibration if estimates of absolute risks were to be given to individuals.Conclusions: Several risk models based on easily obtainable data have relatively good discrimination in a UK population. Modelling studies are now required to estimate the potential health benefits and cost-effectiveness of implementing stratified risk-based CRC screening. [ABSTRACT FROM AUTHOR]

Background: In England, 'fast-track' (also known as 'two-week wait') general practitioner referrals for suspected cancer in symptomatic patients are used to shorten diagnostic intervals and are supported by clinical guidelines. However, the use of the fast-track pathway may vary for different patient groups.Methods: We examined data from 669 220 patients with 35 cancers diagnosed in 2006-2010 following either fast-track or 'routine' primary-to-secondary care referrals using 'Routes to Diagnosis' data. We estimated the proportion of fast-track referrals by sociodemographic characteristic and cancer site and used logistic regression to estimate respective crude and adjusted odds ratios. We additionally explored whether sociodemographic associations varied by cancer.Results: There were large variations in the odds of fast-track referral by cancer (P<0.001). Patients with testicular and breast cancer were most likely to have been diagnosed after a fast-track referral (adjusted odds ratios 2.73 and 2.35, respectively, using rectal cancer as reference); whereas patients with brain cancer and leukaemias least likely (adjusted odds ratios 0.05 and 0.09, respectively, for brain cancer and acute myeloid leukaemia). There were sex, age and deprivation differences in the odds of fast-track referral (P<0.013) that varied in their size and direction for patients with different cancers (P<0.001). For example, fast-track referrals were least likely in younger women with endometrial cancer and in older men with testicular cancer.Conclusions: Fast-track referrals are less likely for cancers characterised by nonspecific presenting symptoms and patients belonging to low cancer incidence demographic groups. Interventions beyond clinical guidelines for 'alarm' symptoms are needed to improve diagnostic timeliness. [ABSTRACT FROM AUTHOR]

Background: Rural Australians have poorer survival for most common cancers, due partially to later diagnosis. Internationally, several initiatives to improve cancer outcomes have focused on earlier presentation to healthcare and timely diagnosis. We aimed to measure the effect of community-based symptom awareness and general practice-based educational interventions on the time to diagnosis in rural patients presenting with breast, prostate, colorectal or lung cancer in Western Australia.Methods: 2 × 2 factorial cluster randomised controlled trial. Community Intervention: cancer symptom awareness campaign tailored for rural Australians. GP intervention: resource card with symptom risk assessment charts and local cancer referral pathways implemented through multiple academic detailing visits. Trial Area A received the community symptom awareness and Trial Area B acted as the community campaign control region. Within both Trial Areas general practices were randomised to the GP intervention or control.Primary Outcome: total diagnostic interval (TDI).Results: 1358 people with incident breast, prostate, colorectal or lung cancer were recruited. There were no significant differences in the median or ln mean TDI at either intervention level (community intervention vs control: median TDI 107.5 vs 92 days; ln mean difference 0.08 95% CI -0.06-0.23 P=0.27; GP intervention vs control: median TDI 97 vs 96.5 days; ln mean difference 0.004 95% CI -0.18-0.19 P=0.99). There were no significant differences in the TDI when analysed by factorial design, tumour group or sub-intervals of the TDI.Conclusions: This is the largest trial to test the effect of community campaign or GP interventions on timeliness of cancer diagnosis. We found no effect of either intervention. This may reflect limited dose of the interventions, or the limited duration of follow-up. Alternatively, these interventions do not have a measurable effect on time to cancer diagnosis. [ABSTRACT FROM AUTHOR]

A rare event has been identified in a brief detection of X-rays. Serendipity only pays off when you know what to do with it, and researchers have used the finding to verify a long-standing theory about a class of exploding star.Brief detection of X-rays confirms prediction for classical novae. [ABSTRACT FROM AUTHOR]

Purpose: Sacrectomy is a highly demanding surgery representing the main treatment for primary tumors arising in the sacrum and pelvis. Unfortunately, it is correlated with loss of important function depending on the resection level and nerve roots sacrificed. The current literature regarding residual function after sacral resection comes from several small case series. The goal of this review is to appraise residual motor function and gait, sensitivity, bladder, bowel, and sexual function after sacrectomies, with consideration to the specific roots sacrificed.Methods: An exhaustive literature search was conducted. All manuscripts published before May 2015 regarding residual function after sacrectomy were considered; if a clear correlation between root level and functioning was not present, the paper was excluded. The review identified 15 retrospective case series, totaling 244 patients; 42 patients underwent sacrectomies sparing L4/L4, L4/L5 and L5/L5; 45 sparing both L5 and one or both S1 roots; 8 sparing both S1 and one S2; 48 sparing both S2; 11 sparing both S2 and one S3, 54 sparing both S3, 9 sparing both S3 and one or both S4, and 27 underwent unilateral variable resection.Results: Patients who underwent a sacrectomy maintained functionally normal ambulation in 56.2 % of cases when both S2 roots were spared, 94.1 % when both S3 were spared, and in 100 % of more distal resections. Normal bladder and bowel function were not present when both S2 were cut. When one S2 root was spared, normal bladder function was present in 25 % of cases; when both S2 were spared, 39.9 %; when one S3 was spared, 72.7 %; and when both S3 were spared, 83.3 %. Abnormal bowel function was present in 12.5 % of cases when both S1 and one S2 were spared; in 50.0 % of cases when both S2 were spared; and in 70 % of cases when one S3 was spared; if both S3 were spared, bowel function was normal in 94 % of cases. When even one S4 root was spared, normal bladder and bowel function were present in 100 % of cases. Unilateral sacral nerve root resection preserved normal bladder function in 75 % of cases and normal bowel function in 82.6 % of cases. Motor function depended on S1 root involvement.Conclusion: Total sacrectomy is associated with compromising important motor, bladder, bowel, sensitivity, and sexual function. Residual motor function is dependent on sparing L5 and S1 nerve roots. Bladder and bowel function is consistently compromised in higher sacrectomies; nevertheless, the probability of maintaining sufficient function increases progressively with the roots spared, especially when S3 nerve roots are spared. Unilateral resection is usually associated with more normal function. To the best of our knowledge, this is the first comprehensive literature review to analyze published reports of residual sacral nerve root function after sacrectomy. [ABSTRACT FROM AUTHOR]

We report here the novel species Halomonas coralii. The nearly complete genome of strain 362.1T consisted of 4.4 Mbp (3989 CDS; 66.3% GC). Genomic taxonomy analysis demonstrates that the novel strain has < 83% AAI and < 29% GGDH towards its closest neighbors. [ABSTRACT FROM AUTHOR]

Background: The objective of this study is to investigate symptoms, clinical factors and socio-demographic factors associated with colorectal cancer (CRC) diagnosis and time to diagnosis.Methods: Prospective cohort study of participants referred for suspicion of CRC in two English regions. Data were collected using a patient questionnaire, primary care and hospital records. Descriptive and regression analyses examined associations between symptoms and patient factors with total diagnostic interval (TDI), patient interval (PI), health system interval (HSI) and stage.Results: A total of 2677 (22%) participants responded; after exclusions, 2507 remained. Participants were diagnosed with CRC (6.1%, 56% late stage), other cancers (2.0%) or no cancer (91.9%). Half the cohort had a solitary first symptom (1332, 53.1%); multiple first symptoms were common. In this referred population, rectal bleeding was the only initial symptom more frequent among cancer than non-cancer cases (34.2% vs 23.9%, P=0.004). There was no evidence of differences in TDI, PI or HSI for those with cancer vs non-cancer diagnoses (median TDI CRC 124 vs non-cancer 138 days, P=0.142). First symptoms associated with shorter TDIs were rectal bleeding, change in bowel habit, 'feeling different' and fatigue/tiredness. Anxiety, depression and gastro-intestinal co-morbidities were associated with longer HSIs and TDIs. Symptom duration-dependent effects were found for rectal bleeding and change in bowel habit.Conclusions: Doctors and patients respond less promptly to some symptoms of CRC than others. Healthcare professionals should be vigilant to the possibility of CRC in patients with relevant symptoms and mental health or gastro-intestinal comorbidities. [ABSTRACT FROM AUTHOR]

Purpose: Accurate survival estimation is prerequisite to determine the most appropriate treatment for patients with metastatic spine disease. Several authors have proposed classification systems analyzing clinical and radiological parameters, such as, performance status, metastasis localization, and primary tumor histotype, but the modified Tokuhashi score (mTS) is the most widely used. Although it is regarded as one of the most complete and accurate systems, it does not take the effectiveness of new therapeutic strategies into consideration, contributing to a progressive loss of accuracy. The purpose of this review is to verify the ability of the mTS to accurately estimate metastatic spine patient survival, nearly 10 years after it was introduced.Methods: A literature review was conducted to evaluate mTS accuracy to predict metastatic spine patient survival.Results: Ten studies were selected, representing 1686 patients. The total predictive accuracy of the mTS was 63.00%; for patients expected to survive less than 6 months (group I), it was 64.10%; 6-12 months (group II), 55.32%; and more than 12 months (group III), 77.21%. A progressive decrease in accuracy over time was statistically significant in groups I and II.Conclusions: The mTS is suggestive of actual survival for patients with a good prognosis. It is less accurate for patients with an estimated survival of less than 12 months. The decreasing trend in mTS accuracy over time will likely further reduce mTS utility. An important opportunity exists to develop new instruments to assist spine surgeons and oncologists to choose appropriate surgical or non-surgical treatment modalities for patients with metastatic spine disease. [ABSTRACT FROM AUTHOR]

Numerous risk tools are now available, which predict either current or future risk of a cancer diagnosis. In theory, these tools have the potential to improve patient outcomes through enhancing the consistency and quality of clinical decision-making, facilitating equitable and cost-effective distribution of finite resources such as screening tests or preventive interventions, and encouraging behaviour change. These potential uses have been recognised by the National Cancer Institute as an 'area of extraordinary opportunity' and an increasing number of risk prediction models continue to be developed. The data on predictive utility (discrimination and calibration) of these models suggest that some have potential for clinical application; however, the focus on implementation and impact is much more recent and there remains considerable uncertainty about their clinical utility and how to implement them in order to maximise benefits and minimise harms such as over-medicalisation, anxiety and false reassurance. If the potential benefits of risk prediction models are to be realised in clinical practice, further validation of the underlying risk models and research to assess the acceptability, clinical impact and economic implications of incorporating them in practice are needed. [ABSTRACT FROM AUTHOR]

Purpose: The minimally invasive (MI) lateral lumbar interbody fusion (LLIF) approach has become increasingly popular for the treatment of degenerative lumbar spine disease. The neural anatomy of the lumbar plexus has been studied; however, the pertinent surgical vascular anatomy has not been examined in detail. The goal of this study is to examine the vascular structures that are relevant in relation to the MI-LLIF approach.Methods: Anatomic dissection of the lumbar spines and associated vasculature was performed in three embalmed, adult cadavers. Right and left surgeon perspective views during LLIF were for a total of six approaches. During the dissection, all vascular elements were noted and photographed, and anatomical relationships to the vertebral bodies and disc spaces were analyzed. In addition, several axial and sagittal MRI images of the lumbar spine were analyzed to complement the cadaveric analysis.Results: The aorta descends along the left anterior aspect of lumbar vertebra with an average distance of 2.1 cm (range 1.9-2.3 cm) to the center of each intervertebral disc. The vena cava descends along the right anterior aspect of lumbar vertebrates with average distance of 1.4 cm (range 1.3-1.6 cm) to the center of the intervertebral disc. Each vertebral body has two lumbar arteries (direct branches from the aorta); one exits to the left and one to the right side of the vertebral body. The lumbar arteries pass underneath the sympathetic trunk, run in the superior margin of the vertebral body and extend all the way across it, with average length of 3.8 cm (range 2.5-5 cm). The mean distance between the arteries and the inferior plate of the superior disc space is 4.2 mm (range 2-5 mm) and mean distance of 3.1 cm (range 2.8-3.8 cm) between two arteries in adjacent vertebrae. One of the cadavers had an expected normal anatomical variation where the left arteries at L3-L4 anastomosed dorsally of the vertebral bodies at the middle of the intervertebral disc.Conclusions: Understanding the vascular anatomy of the lateral and anterior lumbar spine is paramount for successfully and safely executing the LLIF procedure. It is imperative to identify anatomical variations in lumbar arteries and veins with careful assessment of the preoperative imaging. [ABSTRACT FROM AUTHOR]

Background:This prospective cohort study aimed to identify symptom and patient factors that influence time to lung cancer diagnosis and stage at diagnosis.Methods:Data relating to symptoms were collected from patients upon referral with symptoms suspicious of lung cancer in two English regions; we also examined primary care and hospital records for diagnostic routes and diagnoses. Descriptive and regression analyses were used to investigate associations between symptoms and patient factors with diagnostic intervals and stage.Results:Among 963 participants, 15.9% were diagnosed with primary lung cancer, 5.9% with other thoracic malignancies and 78.2% with non-malignant conditions. Only half the cohort had an isolated first symptom (475, 49.3%); synchronous first symptoms were common. Haemoptysis, reported by 21.6% of cases, was the only initial symptom associated with cancer. Diagnostic intervals were shorter for cancer than non-cancer diagnoses (91 vs 124 days, P=0.037) and for late-stage than early-stage cancer (106 vs 168 days, P=0.02). Chest/shoulder pain was the only first symptom with a shorter diagnostic interval for cancer compared with non-cancer diagnoses (P=0.003).Conclusions:Haemoptysis is the strongest symptom predictor of lung cancer but occurs in only a fifth of patients. Programmes for expediting earlier diagnosis need to focus on multiple symptoms and their evolution. [ABSTRACT FROM AUTHOR]

Background:Reducing diagnostic delays in primary care by improving the assessment of symptoms associated with cancer could have significant impacts on cancer outcomes. Symptom risk assessment tools could improve the diagnostic assessment of patients with symptoms suggestive of cancer in primary care. We aimed to explore the use of a cancer risk tool, which implements the QCancer model, in consultations and its potential impact on clinical decision making.Methods:We implemented an exploratory 'action design' method with 15 general practitioners (GPs) from Victoria, Australia. General practitioners applied the risk tool in simulated consultations, conducted semi-structured interviews based on the normalisation process theory and explored issues relating to implementation of the tool.Results:The risk tool was perceived as being potentially useful for patients with complex histories. More experienced GPs were distrustful of the risk output, especially when it conflicted with their clinical judgement. Variable interpretation of symptoms meant that there was significant variation in risk assessment. When a risk output was high, GPs were confronted with numerical risk outputs creating challenges in consultation.Conclusions:Significant barriers to implementing electronic cancer risk assessment tools in consultation could limit their uptake. These relate not only to the design and integration of the tool but also to variation in interpretation of clinical histories, and therefore variable risk outputs and strong beliefs in personal clinical intuition. [ABSTRACT FROM AUTHOR]