Reconstruction of sea surface temperatures from the oxygen isotope composition of fossil planktic foraminifera.

Knowledge of the historic surface temperature of sea water is of importance for the calibration of climate models. The oxygen isotope composition of the shells of several species of planktic foraminifera can be used as a measure for this sea surface temperature. In this paper we investigate how mathematical models can contribute to the process of extracting information about the temperature at which the foraminifera lived from measurement of the oxygen isotope composition of their shells. A simple model is proposed which captures both the average and the variability of the temperature. Preliminary findings suggest that this model forms a solid basis for future research

Treatment of keratinocyte carcinoma in elderly patients - a review of the current literature

A large percentage of the patients with keratinocyte carcinoma (KC, formerly known as non-melanoma skin cancer) is of advanced age and often too frail for standard therapies. However, no specific treatment recommendations are given for this population. This review aimed to give an overview of the current literature on the best practice for the treatment of elderly patients with KC. A literature search was performed in MEDLINE, using ‘keratinocyte carcinoma’, ‘elderly’, ‘treatment’ and various synonyms. Case reports, reviews, comments, non-English literature and studies with a sample size <15 were excluded. After selection, a total of 47 studies were reviewed. Two types of studies were identified, focusing on (I) the effect of age on treatment outcomes and (II) alternative treatment schedules for elderly patients. Studies on surgery, the gold standard, describe larger lesions and defect size in the elderly population. Recurrence rate, complication rate and disease-specific survival were not affected by age. Depending on the expected morbidity of a suggested (re-)excision and patient preferences, a conservative watchful waiting policy can be agreed upon as a shared decision. Other common treatment modalities, such as adjuvant radiotherapy, photodynamic therapy and systemic therapy for basal cell carcinoma (BCC), show comparable results in the elderly and younger population. Alternative treatment schedules for elderly patients include primary hypofractionated radiotherapy, which seems effective and well-tolerated, although research is limited to case series. Additionally, localized and topical treatments seem safe and effective especially for low-risk tumours. Data are lacking on the efficacy of systemic therapies of metastatic KC in elderly patients. Efficacy of most treatments (with the exception of photodynamic therapy) is not dependent on age. There is need for more research on the efficacy of adjusted treatment modalities, such as hypofractionated radiotherapy and palliative or curative systemic treatment

On the mechanisms governing gas penetration into a tokamak plasma during a massive gas injection

A new 1D radial fluid code, IMAGINE, is used to simulate the penetration of gas into a tokamak plasma during a massive gas injection (MGI). The main result is that the gas is in general strongly braked as it reaches the plasma, due to mechanisms related to charge exchange and (to a smaller extent) recombination. As a result, only a fraction of the gas penetrates into the plasma. Also, a shock wave is created in the gas which propagates away from the plasma, braking and compressing the incoming gas. Simulation results are quantitatively consistent, at least in terms of orders of magnitude, with experimental data for a D 2 MGI into a JET Ohmic plasma. Simulations of MGI into the background plasma surrounding a runaway electron beam show that if the background electron density is too high, the gas may not penetrate, suggesting a possible explanation for the recent results of Reux et al in JET (2015 Nucl. Fusion 55 093013)

Vismodegib voor gevorderd basaalcelcarcinoom:Doelgerichte behandeling bij lokaal uitgebreide of gemetastaseerde tumoren

Het overgrote deel van de patiënten met een basaalcelcarcinoom is eenvoudig curatief te behandelen. Bij lokaal uitgebreide of gemetastaseerde basaalcelcarcinomen is dit echter niet altijd meer mogelijk. Dan is doelgerichte systemische therapie (‘targeted therapy’) een optie. In deze klinische les presenteren wij 3 patiënten met een of meer basaalcelcarcinomen die met succes behandeld werden met vismodegib. Het basaalcelcarcinoom is de meest voorkomende vorm van kanker in Nederland, met 37.500 nieuwe patiënten in 2014, en de incidentie stijgt nog steeds.1 De voorkeursbehandeling is excisie. Voor oppervlakkig groeiende basaalcelcarcinomen zijn daarnaast niet-invasieve therapieën, zoals 5-fluorouracilcrème, imiquimodcrème en fotodynamische therapie, beschikbaar. Voor specifieke patiënten is radiotherapie geïndiceerd. Langer bestaande onbehandelde tumoren kunnen leiden tot een zogenoemd lokaal uitgebreid basaalcelcarcinoom. Curatieve behandeling met chirurgie of radiotherapie is bij deze tumoren soms technisch niet meer mogelijk of heeft grote functionele gevolgen. Metastasering is uiterst zeldzaam (0,003-0,55%) en komt voornamelijk voor bij lokaal uitgebreide basaalcelcarcinomen in het hoofd-halsgebied of .

Eight years of experience with vismodegib for advanced and multiple basal cell carcinoma patients in the Netherlands: a retrospective cohort study

BACKGROUND: Vismodegib has been used for the treatment of locally advanced basal cell carcinoma (laBCC) and metastatic BCC (mBCC) since 2011. Most efficacy and safety data are provided by clinical trials. This study evaluates the effectiveness of vismodegib for the treatment of laBCC, mBCC and basal cell nevus syndrome (BCNS) patients, and the tumour characteristics associated with a higher probability of achieving a complete response in the Netherlands. METHODS: A retrospective cohort study that included all patients ≥18 years with histologically proven basal cell carcinoma that received ≥1 dose of vismodegib between July 2011 and September 2019 in the Netherlands. RESULTS: In total, 48 laBCC, 11 mBCC and 19 BCNS patients were included. Median progression-free survival was 10.3 months (95% confidence interval (CI), 7.5-22.6) for laBCC, 11.7 (95% CI, 5.2-17.5) for mBCC and 19.1 (95% CI, 7.4-20.2) for BCNS. Larger laBCCs were associated with a lower probability of complete response (hazard ratio (HR) 0.77 per increase in cm, p = 0.02). Of all BCNS patients, 63% received ≥2 treatment sequences with vismodegib; all achieved partial responses. CONCLUSIONS: Half of the aBCC patients progress within 1 year after the start of vismodegib treatment. More research is needed to investigate other treatment strategies after vismodegib progression and to evaluate long-term effects of repetitive vismodegib treatment