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

Erratum to: Logarithmic accuracy of parton showers: a fixed-order study

ERRATUM TO: JHEP09(2018)033 https://doi.org/10.1007/JHEP09(2018)03

Do big athletes have big hearts? Impact of extreme anthropometry upon cardiac hypertrophy in professional male athletes.

AIM: Differentiating physiological cardiac hypertrophy from pathology is challenging when the athlete presents with extreme anthropometry. While upper normal limits exist for maximal left ventricular (LV) wall thickness (14 mm) and LV internal diameter in diastole (LVIDd, 65 mm), it is unknown if these limits are applicable to athletes with a body surface area (BSA) >2.3 m(2). PURPOSE: To investigate cardiac structure in professional male athletes with a BSA>2.3 m(2), and to assess the validity of established upper normal limits for physiological cardiac hypertrophy. METHODS: 836 asymptomatic athletes without a family history of sudden death underwent ECG and echocardiographic screening. Athletes were grouped according to BSA (Group 1, BSA>2.3 m(2), n=100; Group 2, 2-2.29 m(2), n=244; Group 3, 13 mm, but in combination with an abnormal ECG suspicious of an inherited cardiac disease. CONCLUSION: Regardless of extreme anthropometry, established upper limits for physiological cardiac hypertrophy of 14 mm for maximal wall thickness and 65 mm for LVIDd are clinically appropriate for all athletes. However, the abnormal ECG is key to diagnosis and guides follow-up, particularly when cardiac dimensions are within accepted limits

Symptoms and patient factors associated with diagnostic intervals for pancreatic cancer (SYMPTOM pancreatic study): a prospective cohort study

This is the final version. Available on open access from Elsevier via the DOI in this recordBackground Pancreatic cancer is the tenth most common cancer in the UK; however, outcomes are poor, in part due to late diagnosis. We aimed to identify symptoms and other clinical and sociodemographic factors associated with pancreatic cancer diagnosis and diagnostic intervals. Methods We did this prospective cohort study at seven hospitals in two regions in England. We recruited participants aged 40 years or older who were referred for suspicion of pancreatic cancer. Data were collected by use of a patient questionnaire and primary care and hospital records. Descriptive and regression analyses were done to examine associations between symptoms and patient factors with the total diagnostic interval (time from onset of the first symptom to the date of diagnosis), comprising patient interval (time from first symptom to first presentation) and health system interval (time from first presentation to diagnosis). Findings We recruited 391 participants between Jan 1, 2011, and Dec 31, 2014 (24% response rate). 119 (30%) participants were diagnosed with pancreatic cancer (41 [34%] had metastatic disease), 47 (12%) with other cancers, and 225 (58%) with no cancer. 212 (54%) patients had multiple first symptoms whereas 161 (41%) patients had a solitary first symptom. In this referred population, no initial symptoms were reported more frequently by patients with cancer than by those with no cancer. Several subsequent symptoms predicted pancreatic cancer: jaundice (51 [49%] of 105 patients with pancreatic cancer vs 25 [12%] of 211 patients with no cancer; p<0·0001), fatigue (48/95 [51%] vs 40/155 [26%]; p=0·0001), change in bowel habit (36/87 [41%] vs 28/175 [16%]; p<0·0001), weight loss (55/100 [55%] vs 41/184 [22%]; p<0·0001), and decreased appetite (41/86 [48%] vs 41/156 [26%]; p=0·0011). There was no difference in any interval between patients with pancreatic cancer and those with no cancer (total diagnostic interval: median 117 days [IQR 57–234] vs 131 days [IQR 66–284]; p=0·32; patient interval 18 days [0–37] vs 15 days [1–62]; p=0·22; health system interval 76 days [28–161] vs 79 days [30–156]; p=0·68). Total diagnostic intervals were shorter when jaundice (hazard ratio [HR] 1·38, 95% CI 1·07–1·78; p=0·013) and decreased appetite (1·42, 1·11–1·82; p=0·0058) were reported as symptoms, and longer in patients presenting with indigestion (0·71, 0·56–0·89; p=0·0033), back pain (0·77, 0·59–0·99; p=0·040), diabetes (0·71, 0·52–0·97; p=0·029), and self-reported anxiety or depression, or both (0·67, 0·49–0·91; p=0·011). Health system intervals were likewise longer with indigestion (0·74, 0·58–0·95; p=0·0018), back pain (0·76, 0·58–0·99; p=0·044), diabetes (0·63, 0·45–0·89; p=0·0082), and self-reported anxiety or depression, or both (0·63, 0·46–0·88; p=0·0064), but were shorter with male sex (1·41, 1·1–1·81; p=0·0072) and decreased appetite (1·56, 1·19–2·06; p=0·0015). Weight loss was associated with longer patient intervals (HR 0·69, 95% CI 0·54–0·89; p=0·0047). Interpretation Although we identified no initial symptoms that differentiated people diagnosed with pancreatic cancer from those without pancreatic cancer, key additional symptoms might signal the disease. Health-care professionals should be vigilant to the possibility of pancreatic cancer in patients with evolving gastrointestinal and systemic symptoms, particularly in those with diabetes or mental health comorbidities. Funding National Institute for Health Research and Pancreatic Cancer Action.National Institute for Health Research (NIHR

Analyzing redshift surveys to measure the power spectrum on large scales

Upcoming large redshift surveys potentially allow precision measurements of the galaxy power spectrum. To accurately measure P(k) on the largest scales, comparable to the depth of the survey, it is crucial that finite volume effects are accurately corrected for in the data analysis. Here we derive analytic expressions for the one such effect that has not previously been worked out exactly: that of the so-called integral constraint. We also show that for data analysis methods based on counts in cells, multiple constraints can be included via simple matrix operations, thereby rendering the results less sensitive to galactic extinction and misestimates of the shape of the radial selection function.Comment: Mostly superseded by astro-ph/9708020; from 5/5-97. 10 pages, with 1 figure included. More detailed treatment at http://www.sns.ias.edu/~max/galpower.html (faster from the US), from http://www.mpa-garching.mpg.de/~max/galpower.html (faster from Europe) or from [email protected]

Planet Formation by Coagulation: A Focus on Uranus and Neptune

Planets form in the circumstellar disks of young stars. We review the basic physical processes by which solid bodies accrete each other and alter each others' random velocities, and we provide order-of-magnitude derivations for the rates of these processes. We discuss and exercise the two-groups approximation, a simple yet powerful technique for solving the evolution equations for protoplanet growth. We describe orderly, runaway, neutral, and oligarchic growth. We also delineate the conditions under which each occurs. We refute a popular misconception by showing that the outer planets formed quickly by accreting small bodies. Then we address the final stages of planet formation. Oligarchy ends when the surface density of the oligarchs becomes comparable to that of the small bodies. Dynamical friction is no longer able to balance viscous stirring and the oligarchs' random velocities increase. In the inner-planet system, oligarchs collide and coalesce. In the outer-planet system, some of the oligarchs are ejected. In both the inner- and outer-planet systems, this stage ends once the number of big bodies has been reduced to the point that their mutual interactions no longer produce large-scale chaos. Subsequently, dynamical friction by the residual small bodies circularizes and flattens their orbits. The final stage of planet formation involves the clean up of the residual small bodies. Clean up has been poorly explored.Comment: to appear in ARA&A (2004), 51 pages, 3 figure

FAN1 controls mismatch repair complex assembly via MLH1 retention to stabilize CAG repeat expansion in Huntington's disease

CAG repeat expansion in the HTT gene drives Huntington’s disease (HD) pathogenesis and is modulated by DNA damage repair pathways. In this context, the interaction between FAN1, a DNA-structure-specific nuclease, and MLH1, member of the DNA mismatch repair pathway (MMR), is not defined. Here, we identify a highly conserved SPYF motif at the N terminus of FAN1 that binds to MLH1. Our data support a model where FAN1 has two distinct functions to stabilize CAG repeats. On one hand, it binds MLH1 to restrict its recruitment by MSH3, thus inhibiting the assembly of a functional MMR complex that would otherwise promote CAG repeat expansion. On the other hand, it promotes accurate repair via its nuclease activity. These data highlight a potential avenue for HD therapeutics in attenuating somatic expansion

Aerobic capacity, activity levels and daily energy expenditure in male and female adolescents of the kenyan nandi sub-group

The relative importance of genetic and socio-cultural influences contributing to the success of east Africans in endurance athletics remains unknown in part because the pre-training phenotype of this population remains incompletely assessed. Here cardiopulmonary fitness, physical activity levels, distance travelled to school and daily energy expenditure in 15 habitually active male (13.9±1.6 years) and 15 habitually active female (13.9±1.2) adolescents from a rural Nandi primary school are assessed. Aerobic capacity ([Formula: see text]) was evaluated during two maximal discontinuous incremental exercise tests; physical activity using accelerometry combined with a global positioning system; and energy expenditure using the doubly labelled water method. The [Formula: see text] of the male and female adolescents were 73.9±5.7 ml(.) kg(-1.) min(-1) and 61.5±6.3 ml(.) kg(-1.) min(-1), respectively. Total time spent in sedentary, light, moderate and vigorous physical activities per day was 406±63 min (50% of total monitored time), 244±56 min (30%), 75±18 min (9%) and 82±30 min (10%). Average total daily distance travelled to and from school was 7.5±3.0 km (0.8-13.4 km). Mean daily energy expenditure, activity-induced energy expenditure and physical activity level was 12.2±3.4 MJ(.) day(-1), 5.4±3.0 MJ(.) day(-1) and 2.2±0.6. 70.6% of the variation in [Formula: see text] was explained by sex (partial R(2) = 54.7%) and body mass index (partial R(2) = 15.9%). Energy expenditure and physical activity variables did not predict variation in [Formula: see text] once sex had been accounted for. The highly active and energy-demanding lifestyle of rural Kenyan adolescents may account for their exceptional aerobic fitness and collectively prime them for later training and athletic success

The 'At-risk mental state' for psychosis in adolescents : clinical presentation, transition and remission.

Despite increased efforts over the last decade to prospectively identify individuals at ultra-high risk of developing a psychotic illness, limited attention has been specifically directed towards adolescent populations (<18 years). In order to evaluate how those under 18 fulfilling the operationalised criteria for an At-Risk Mental State (ARMS) present and fare over time, we conducted an observational study. Participants (N = 30) generally reported a high degree of functional disability and frequent and distressing perceptual disturbance, mainly in the form of auditory hallucinations. Seventy percent (21/30) were found to fulfil the criteria for a co-morbid ICD-10 listed mental health disorder, with mood (affective; 13/30) disorders being most prevalent. Overall transition rates to psychosis were low at 24 months follow-up (2/28; 7.1 %) whilst many participants demonstrated a significant reduction in psychotic-like symptoms. The generalisation of these findings may be limited due to the small sample size and require replication in a larger sample