Nitrogen deposition shows no consistent negative nor positive effect on the response of forest productivity to drought across European FLUXNET forest sites

Atmospheric reactive nitrogen (N) deposition is an important driver of carbon (C) sequestration in forest ecosystems. Previous studies have focused on N-C interactions in various ecosystems; however, relatively little is known about the impact of N deposition on ecosystem C cycling during climate extremes such as droughts. With the occurrence and severity of droughts likely to be exacerbated by climate change, N deposition—drought interactions remain one of the key uncertainties in process-based models to date. This study aims to contribute to the understanding of N deposition-drought dynamics on gross primary production (GPP) in European forest ecosystems. To do so, different soil water availability indicators (Standardized Precipitation Evapotranspiration Index (SPEI), soil volumetric water) and GPP measurements from European FLUXNET forest sites were used to quantify the response of forest GPP to drought. The computed drought responses of the forest GPP to drought were linked to modelled N deposition estimates for varying edaphic, physiological, and climatic conditions. Our result showed a differential response of forest ecosystems to the drought indicators. Although all FLUXNET forest sites showed a coherent dependence of GPP on N deposition, no consistent or significant N deposition effect on the response of forest GPP to drought could be isolated. The mean response of forest GPP to drought could be predicted for forests with Pinus trees as dominant species (R2 = 0.85, RMSE = 8.1). After extracting the influence of the most prominent parameters (mean annual temperature and precipitation, forest age), however, the variability remained too large to significantly substantiate hypothesized N deposition effects. These results suggest that, while N deposition clearly affects forest productivity, N deposition is not a major nor consistent driver of forest productivity responses to drought in European forest ecosystems

Adolescents and Young Adults Living With an Uncertain or Poor Cancer Prognosis:The "New" Lost Tribe

Historically, adolescent and young adult (AYA) patients with cancer, diagnosed for the first time at age 15 through 39 years, have often been identified as a "lost tribe" without a medical "home"; neither pediatric nor adult oncology services were able to provide ageappropriate care to this specific group. Internationally, AYA care programs are being established to bridge the gap between the age-defined healthcare worlds and to address the specific needs of AYAs with cancer. However, AYA care programs mostly focus on improving cure rates and addressing survivorship issues, and direct less attention to the unique needs of those living with an uncertain and/or poor cancer prognosis. Additionally, palliative care services are typically poorly equipped to address the age-specific needs of this group. Given that increasingly more AYAs with an uncertain and/or poor cancer prognosis are gaining life years because of novel treatments, and sometimes even face the prospect of longterm disease control, AYA care programs should address the unique palliative care needs of this "new" lost tribe within AYA oncology. This report provides a definition and description of the AYA population living with an uncertain and/or poor cancer prognosis in terms of epidemiologic, clinical, and psychosocial characteristics and challenges, and provides perspectives for future research and care initiatives. It also highlights the need to comprehensively examine the experience of AYAs who are living with uncertain and/or poor cancer prognosis to adjust best care practices for this unique group

99mTc-sestamibi is a substrate for P-glycoprotein and the multidrug resistance-associated protein.

99mTc-sestamibi (99mTc-MIBI) is a substrate for the P-glycoprotein (P-gp) pump but it is not known whether it is a substrate for the multidrug resistance-associated protein (MRP) pump. Therefore, 99mTc-MIBI was evaluated in the GLC4 cell line and its doxorubicin-resistant MRP-, but not P-gp-, overexpressing GLC4/ADR sublines as well as in the S1 cell line and its MRP-transfected subline S1-MRP. 99mTc-MIBI concentration decreased in the GLC4/ADR sublines with increasing MRP overexpression and was lower in S1-MRP than in S1. 99mTc-MIBI plus vincristine increased 99mTc-MIBI concentration in GLC4 lines compared with 99mTc-MIBI alone. 99mTc-MIBI efflux raised with increasing MRP expression in the GLC4 lines. Glutathione depletion elevated 99mTc-MIBI concentration in GLC4/ADR150x. Cross resistance for 99Tc-MIBI, used to test cytotoxicity of the Tc compound, was observed in GLC4/ADR150x vs GLC4. 99Tc-MIBI induced a synergistic effect on vincristine cytotoxicity in GLC4/ADR150x. These results show that 99mTc-MIBI is involved in MRP-mediated efflux. The fact that 99mTc-MIBI efflux is influenced by MDR1 and MRP expression must be taken into account when this gamma-rays-emitting complex is tested for tumour efflux measurements

Pain is a risk factor for common mental disorders. Results from the Netherlands Mental Health Survey and Incidence Study-2: a longitudinal, population-based study

Pain might be an important risk factor for common mental disorders. Insight into the longitudinal association between pain and common mental disorders in the general adult population could help improve prevention and treatment strategies. Data were used from the first 2 waves of the Netherlands Mental Health Survey and Incidence Study-2, a psychiatric epidemiological cohort study among the Dutch general population aged 18 to 64 years at baseline (N = 5303). Persons without a mental disorder 12 months before baseline were selected as the at-risk group (n = 4974 for any mood disorder; n = 4979 for any anxiety disorder; and n = 5073 for any substance use disorder). Pain severity and interference due to pain in the past month were measured at baseline using the Short Form Health Survey. DSM-IV mental disorders were assessed at both waves using the Composite International Diagnostic Interview version 3.0. Moderate to very severe pain was associated with a higher risk of mood (odds ratio [OR] = 2.10, 95% confidence interval [CI] = 1.33-3.29) or anxiety disorders (OR = 2.12, 95% CI = 1.27-3.55). Moderate to very severe interference due to pain was also associated with a higher risk of mood (OR = 2.14, 95% CI = 1.30-3.54) or anxiety disorders (OR = 1.92, 95% CI = 1.05-3.52). Pain was not significantly associated with substance use disorders. No interaction effects were found between pain severity or interference due to pain and a previous history of mental disorders. Moderate to severe pain and interference due to pain are strong risk factors for first-incident or recurrent mood and anxiety disorders, independent of other mental disorders. Pain management programs could therefore possibly also serve as a preventative program for mental disorders

Treatment of advanced seminoma with cyclophosphamide, vincristine and carboplatin on an outpatient basis.

This study describes the efficacy and toxicity of a combination regimen consisting of cyclophosphamide, vincristine (oncovin) and carboplatin (COC) for advanced seminoma on an outpatient basis. Twenty-seven patients (mean age 43 years, range 28-63 years) were classified as stage IIC (n = 5), stage IID (n = 12), stage III (n = 9) or stage IV (n = 1). Six had been treated with prior radiotherapy; elevated beta-HCG and elevated LDH serum levels were observed in 15 and 25 patients respectively. Patients were treated with four cycles of 750 mg m-2 cyclophosphamide intravenously (i.v.), 1.4 mg m-2 vincristine i.v. (maximum 2 mg) and carboplatin adjusted to creatinine clearance. Cycles were given at 3 week intervals. The median dose of carboplatin administered was 400 mg m-2 (range 300-450 mg m-2). Six patients [22%; 95% confidence interval (CI), 6-38%] achieved a complete response (CR), 19 (70%; 95% CI, 51-88%) a partial response and two (8%; 95% CI, 0 18%) showed only a response in tumour markers but not a reduction of retroperitoneal mass (NR). Post-chemotherapeutic masses were not removed surgically or irradiated. After a median follow-up of 26 months (range 5-69 months), two patients have died, one from cardiac arrest 2 years after achieving CR, the other with relapsed seminoma 5 months after therapy. None of the other patients relapsed. Main toxicity was haematological, with 22 patients (81%) experiencing thrombocytopenia WHO grade III/IV and 27 (100%) leucocytopenia WHO grade III/IV, requiring dose reduction in five patients. Seven patients experienced granulocytopenic fever. Non-haematological toxicity was rare. Peripheral neuropathy grade I was observed in four patients and grade III in one. Haemorrhagic cystitis occurred once. In conclusion, despite considerable haematological toxicity, COC is feasible on an outpatient basis, even after prior radiotherapy, and is an effective regimen for advanced seminoma with only 1/27 treatment failures after a median follow-up of 26 months

Differential expression of DNA topoisomerase II alpha and -beta in P-gp and MRP-negative VM26, mAMSA and mitoxantrone-resistant sublines of the human SCLC cell line GLC4.

Sublines of the human small-cell lung carcinoma (SCLC) cell line GLC4 with acquired resistance to teniposide, amsacrine and mitoxantrone (GLC4/VM20x, GLC4/AM3x and GLC4/MIT60x, respectively) were derived to study the contribution of DNA topoisomerase II alpha and -beta (TopoII alpha and -beta) to resistance for TopoII-targeting drugs. The cell lines did not overexpress P-glycoprotein or the multidrug resistance-associated protein but were cross-resistant to other TopoII drugs. GLC4/VM20x showed a major decrease in TopoII alpha protein (54%; for all assays presented in this paper the GLC4 level was defined to be 100%) without reduction in TopoII beta protein; GLC4/AM3x showed only a major decrease in TopoII beta protein (to 18%) and not in TopoII alpha. In GLC4/MIT60x, the TopoII alpha and -beta protein levels were both decreased (TopoII alpha to 31%; TopoII beta protein was undetectable). The decrease in TopoII alpha protein in GLC4/VM20x and GLC4/MIT60x, was mediated by decreased TopoII alpha mRNA levels. Loss of TopoII alpha gene copies contributed to the mRNA decrease in these cell lines. Only in the GLC4/MIT60x cell line was an accumulation defect observed for the drug against which the cell line was made resistant. In conclusion, TopoII alpha and -beta levels were decreased differentially in the resistant cell lines, suggesting that resistance to these drugs may be mediated by a decrease in a specific isozyme

Ultra-thin corrugated metamaterial film as large-area transmission dynode

Large-area transmission dynodes were fabricated by depositing an ultra-thin continuous film on a silicon wafer with a 3-dimensional pattern. After removing the silicon, a corrugated membrane with enhanced mechanical properties was formed. Mechanical materials, such as this corrugated membrane, are engineered to improve its strength and robustness, which allows it to span a larger surface in comparison to flat membranes while the film thickness remains constant. The ultra-thin film consists of three layers (Al$_2$O$_3$ /TiN/Al$_2$O$_3$) and is deposited by atomic layer deposition (ALD). The encapsulated TiN layer provides in-plane conductivity, which is needed to sustain secondary electron emission. Two types of corrugated membranes were fabricated: a hexagonal honeycomb and an octagonal pattern. The latter was designed to match the square pitch of a CMOS pixel chip. The transmission secondary electron yield was determined with a collector-based method using a scanning electron microscope. The highest transmission electron yield was measured on a membrane with an octagonal pattern. A yield of 2.15 was achieved for 3.15 keV incident electrons for an Al$_2$O$_3$ /TiN/Al$_2$O$_3$ tri-layer film with layer thicknesses of 10/5/15 nm. The variation in yield across the surface of the corrugated membrane was determined by constructing a yield map. The active surface for transmission secondary electron emission is near 100%, i.e. a primary electron generates transmission secondary electrons regardless of the point of impact on the corrugated membrane