Better surgical techniques, chemotherapy and biological therapy have improved survival in patients with colorectal cancer (CRC), most markedly in younger patients. About half of patients over ...70 years receive dose reductions or early treatment discontinuation of the planned adjuvant or first-line treatment due to side effects. The Comprehensive Geriatric Assessment (CGA) is a multidisciplinary evaluation of an elderly individual's health status. This assessment in older patients with cancer can predict survival, chemotherapy toxicity and morbidity.
This randomized phase II trial (GERICO) is designed to investigate whether comprehensive geriatric assessment and intervention before and during treatment with chemotherapy in frail elderly patients with stages II-IV CRC will increase the number of patients completing chemotherapy. All patients ≥70 years in whom chemotherapy for CRC is planned to start at Herlev and Gentofte Hospital are screened for frailty using the G8 questionnaire at the first visit to the outpatient clinic. The G8 questionnaire is a multi-domain screening tool to identify frail or vulnerable patients at risk of increased toxicity and morbidity. Frail patients are offered inclusion and are then randomized to two groups (the intervention group and the control group). Patients in the intervention group receive a full geriatric assessment of comorbidity, medication, psycho-cognitive function, physical, functional and nutrition status, and interventions are undertaken on identified health issues. Simultaneously, they are treated for their cancer according to international guidelines. Patients in the control group receive the same chemotherapy regimens and standard of care. Primary outcome is number of patients completing scheduled chemotherapy at starting dose. Secondary outcomes are dose reductions, treatment delays, toxicity, time to recurrence, survival, cancer-related mortality and quality of life.
This ongoing trial is one of the first to evaluate the effect of geriatric intervention in frail elderly patients with CRC. The trial will provide new and valuable knowledge about whether it is beneficial for the elderly patient undergoing chemotherapy to be treated simultaneously by a geriatrician.
ClinicalTrials.gov ID: NCT02748811 . The trial was registered retrospectively; registration date 04/28/2016.
The Mars Advanced Radar for Subsurface and Ionospheric Sounding aboard Mars Express has been in operation for over 2 years. Between 14 August 2005 and 31 July 2007, we obtain 34,492 ionospheric ...traces, of which 14,060 yield electron density profiles and 12,291 yield acceptable fits to the Chapman ionospheric model. These results are used to study the Martian ionosphere under changing conditions: the presence or absence of solar energetic particles, solar EUV flux, season, solar zenith angle, and latitude. The 2‐year average subsolar maximum electron density n0 is 1.62 × 105 cm−3, the average subsolar electron density altitude h0 is 128.2 km, and the average neutral scale height H is 12.9 km. Solar energetic particle events are associated with a 6% increase in n0, a 3 km decrease in h0, and a 0–7 km decrease in H. The value of n0 varies smoothly between 1.4 × 105 and 1.8 × 105 cm−3, yielding d ln n0/d ln F10.7 = 0.30 ± 0.4; h0 varies between 115 and 135 km, while H remains relatively constant with EUV flux and season, in contrast with previous work. The value of h0 decreases toward the terminator at low latitude but increases poleward during summer; H varies from 11 km, for solar zenith angle less than 40°, to between 14 and 17 km near the terminator, depending on season. Near‐peak temperatures vary between 220 K and 300 K, less variation than indicated by modeling, probably due to sampling near solar minimum.
ABSTRACT
SuperWASP, the Northern hemisphere WASP observatory, has been observing the skies from La Palma since 2004. In that time, more than 50 planets have been discovered with data contributions ...from SuperWASP. In the process of validating planets, many false-positive candidates have also been identified. The TESS telescope is set to begin observations of the northern sky in 2019. Similar to the WASP survey, the TESS pixel size is relatively large (13 arcsec for WASP and 21 arcsec for TESS), making it susceptible to many blended signals and false detections caused principally by grazing and blended stellar eclipsing binary systems. In order to reduce duplication of effort on targets, we present a catalogue of 1 041 Northern hemisphere SuperWASP targets that have been rejected as planetary transits through follow-up observation.
The Transiting Exoplanet Survey Satellite, TESS, is currently carrying out an all-sky search for small planets transiting bright stars. In the first year of the TESS survey, a steady progress was ...made in achieving the mission’s primary science goal of establishing bulk densities for 50 planets smaller than Neptune. During that year, the TESS’s observations were focused on the southern ecliptic hemisphere, resulting in the discovery of three mini-Neptunes orbiting the star TOI-125, a V = 11.0 K0 dwarf. We present intensive HARPS radial velocity observations, yielding precise mass measurements for TOI-125b, TOI-125c, and TOI-125d. TOI-125b has an orbital period of 4.65 d, a radius of 2.726 ± 0.075 R(E), a mass of 9.50 ± 0.88 M(E), and is near the 2:1 mean motion resonance with TOI-125c at 9.15 d. TOI-125c has a similar radius of 2.759 ± 0.10 R(E) and a mass of 6.63 ± 0.99 M(E), being the puffiest of the three planets. TOI-125d has an orbital period of 19.98 d and a radius of 2.93 ± 0.17 R(E) and mass 13.6 ± 1.2 M(E). For TOI-125b and d, we find unusual high eccentricities of 0.19 ± 0.04 and 0.17(sup +0.08, sub −0.06), respectively. Our analysis also provides upper mass limits for the two low-SNR planet candidates in the system; for TOI-125.04 (R(P) = 1.36 R(E), P = 0.53 d), we find a 2σ upper mass limit of 1.6 M(E), whereas TOI-125.05 (R(P) = 4.2(sup +2.4, sub −1.4 R(E), P = 13.28 d) is unlikely a viable planet candidate with an upper mass limit of 2.7 M(E). We discuss the internal structure of the three confirmed planets, as well as dynamical stability and system architecture for this intriguing exoplanet system.
Treatment of patients with locally advanced rectal cancer (LARC) is based on a combination of chemo-radiotherapy (CRT) and surgery. The rate of distant recurrences remains over 25%. Circulating ...cell-free DNA (cfDNA) in plasma is a mixture of normal and cancer-specific DNA segments and is a promising biomarker in patients with colorectal cancer. The aim of our study was to investigate plasma cfDNA as a prognostic marker for outcome in patients with LARC treated with neoadjuvant CRT and surgery.
In total, 123 patients with LARC were included in 2 biomarker studies. Patients were treated with neoadjuvant CRT before TME surgery. Fifty-two (42%) of the patients received induction chemotherapy with capecitabine+oxaliplatin. Total cfDNA was measured by direct fluorescent assay in EDTA plasma samples obtained at baseline, after induction chemotherapy, and after CRT. Serial samples 5years after surgery were collected in 51 patients (41%).
Median follow-up was 55months. Distant or local recurrence was seen in 30.9% of the patients. Patients with baseline cfDNA levels above the 75th quartile had a higher risk of local or distant recurrence and shorter time to recurrence compared with patients with plasma cfDNA below the 75th percentile (HR=2.48, 95% CI: 1.3–4.8, P=0.007). The same applied to disease-free survival (DFS) (HR=2.43, 95% CI: 1.27–4.7, P=0.015). In multivariate analysis, a high cfDNA level was significantly associated with time to progression and DFS. During follow-up, the association remained significant regardless of time point for sample analysis.
We have demonstrated an association between a high baseline plasma level of cfDNA and increased risk of recurrence, shorter time to recurrence, and shorter DFS in patients with LARC. Consequently, cfDNA could potentially improve pre- and post-treatment risk assessment and facilitate individualized therapy for patients with LARC.
To prevent severe toxicity and hospital admissions, adequate management and recall of information about side effects are crucial and health literacy plays an important role. If age-related factors ...impact recall of given information and handling of side effects, revised ways to give information are required.
We undertook a questionnaire-based survey among 188 newly diagnosed patients with pancreatic cancer or colorectal cancer and chemo-naive patients with prostate cancer treated with adjuvant or first-line palliative chemotherapy comprising satisfaction with given information, recall of potential side effects, and handling of hypothetical side effect scenarios. We evaluated the association between baseline characteristics, ie, age, frailty (G8 score), comorbidity (Charlson Comorbidity Index), cognitive function (Mini-Cog), satisfaction, recall of information, and handling of side effects.
Reduced ability to recall information about several side effects (eg, chest pain) was associated with older age (odds ratio adjusted for cancer aOR 0.94 95% CI, 0.88-0.98) and poor cognitive screening (aOR 0.56 95% CI, 0.33-0.91). Insufficient or dangerous handling of side effects was associated with older age (aOR 0.96 (95% CI, 0.92-0.99)) and cognitive impairment (aOR 0.70 95% CI, 0.50-0.95).
Older age and poor cognitive screening may impact patients' ability to understand and adequately handle chemotherapy-related side effects. Cognitive screening and focus on individual ways to give information including assessment of recall and handling are needed.
Seagrass ecosystems are significant carbon sinks, and their resident microbial communities ultimately determine the quantity and quality of carbon sequestered. However, environmental perturbations ...have been predicted to affect microbial-driven seagrass decomposition and subsequent carbon sequestration. Utilizing techniques including 16S-rDNA sequencing, solid-state NMR and microsensor profiling, we tested the hypothesis that elevated seawater temperatures and eutrophication enhance the microbial decomposition of seagrass leaf detritus and rhizome/root tissues. Nutrient additions had a negligible effect on seagrass decomposition, indicating an absence of nutrient limitation. Elevated temperatures caused a 19% higher biomass loss for aerobically decaying leaf detritus, coinciding with changes in bacterial community structure and enhanced lignocellulose degradation. Although, community shifts and lignocellulose degradation were also observed for rhizome/root decomposition, anaerobic decay was unaffected by temperature. These observations suggest that oxygen availability constrains the stimulatory effects of temperature increases on bacterial carbon remineralization, possibly through differential temperature effects on bacterial functional groups, including putative aerobic heterotrophs (e.g. Erythrobacteraceae, Hyphomicrobiaceae) and sulfate reducers (e.g. Desulfobacteraceae). Consequently, under elevated seawater temperatures, carbon accumulation rates may diminish due to higher remineralization rates at the sediment surface. Nonetheless, the anoxic conditions ubiquitous to seagrass sediments can provide a degree of carbon protection under warming seawater temperatures.
Summary
Purpose
To compare physiological responses of chronic fatigue syndrome (CFS/ME), multiple sclerosis (MS) and healthy controls (HC) following a 24‐h repeated exercise test.
Methods
Ten CFS, ...seven MS and 17 age‐ and gender‐matched healthy controls (10, CFS HC; and seven, MS HC) were recruited. Each participant completed a maximal incremental cycle exercise test on day 1 and again 24 h later. Heart rate (HR), blood pressure (BP), rating of perceived exertion (RPE), oxygen consumption (V˙O2), carbon dioxide production and workload (WL) were recorded. Data analysis investigated these responses at anaerobic threshold (AT) and peak work rate (PWR).
Results
On day 2, both CFS and MS had significantly reduced max workload compared to HC. On day 2, significant differences were apparent in WL between CFS and CFS HC (93 ± 37 W, 132 ± 42 W, P<0·042). CFS workload decreased on day 2, alongside a decrease in HR but with an increase in V˙O2 (ml kg min−1). This was in comparison with an increase in WL, HR and V˙O2 for CFS HC. MS demonstrated a decreased WL compared to MS HC on both days of the study (D1 81 ± 30 W, 116 ±30 W; D2 84 ± 29 W, 118 ± 36 W); however, patients with MS were able to achieve a higher WL on day 2 alongside MS HC.
Conclusion
These results suggest that exercise exhibits a different physiological response in MS and CFS/ME, demonstrating repeated cardiovascular exercise testing as a valid measure for differentiating between fatigue conditions.
Identification of fetal kidney anomalies invites questions about underlying causes and recurrence risk in future pregnancies. We therefore investigated the diagnostic yield of next‐generation ...sequencing in fetuses with bilateral kidney anomalies and the correlation between disrupted genes and fetal phenotypes. Fetuses with bilateral kidney anomalies were screened using an in‐house‐designed kidney‐gene panel. In families where candidate variants were not identified, whole‐exome sequencing was performed. Genes uncovered by this analysis were added to our kidney panel. We identified likely deleterious variants in 11 of 56 (20%) families. The kidney‐gene analysis revealed likely deleterious variants in known kidney developmental genes in 6 fetuses and TMEM67 variants in 2 unrelated fetuses. Kidney histology was similar in the latter 2 fetuses—presenting a distinct prenatal form of nephronophthisis. Exome sequencing identified ROBO1 variants in one family and a GREB1L variant in another family. GREB1L and ROBO1 were added to our kidney‐gene panel and additional variants were identified. Next‐generation sequencing substantially contributes to identifying causes of fetal kidney anomalies. Genetic causes may be supported by histological examination of the kidneys. This is the first time that SLIT‐ROBO signaling is implicated in human bilateral kidney agenesis.
The Transiting Exoplanet Survey Satellite TESS has begun a new age of exoplanet discoveries around bright host stars. We present the discovery of HD 1397b (TOI-120.01), a giant planet in an 11.54-day ...eccentric orbit around a bright (V = 7.9) G-type subgiant. We estimate both host star and planetary parameters consistently using EXOFASTv2 based on TESS time-series photometry of transits and radial velocity measurements with CORALIE and MINERVA-Australis. We also present high angular resolution imaging with NaCo to rule out any nearby eclipsing binaries. We find that HD 1397b is a Jovian planet, with a mass of 0.415 ± 0.020 MJ and a radius of 1.026 ± 0.026 RJ. Characterising giant planets in short-period eccentric orbits, such as HD 1397b, is important for understanding and testing theories for the formation and migration of giant planets as well as planet-star interactions.
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