Body image in adolescent survivors of childhood cancer: The role of chronic health conditions.

BACKGROUND Cancer and its treatment may impair the body image of childhood cancer survivors during adolescence. We compared the body image between adolescent cancer survivors and their siblings, and determined whether survivors' body image is associated with socio-demographic characteristics, clinical characteristics and chronic health conditions. PROCEDURE As part of the nationwide Swiss Childhood Cancer Survivor Study, we sent questionnaires to adolescents (aged 16-19 years), who survived >5 years after having been diagnosed with childhood cancer between 1989 and 2010. Siblings received the same questionnaire. We assessed the level of agreement with three body image statements referring to body satisfaction and preferences for changes. Chronic health conditions were classified into cardiovascular, pulmonary, endocrine, musculoskeletal, renal/digestive, neurological and hearing or vision impairment. We used ordered logistic regression models to identify determinants of a more negative body image. RESULTS Our study included 504 survivors (48% female) with a median age at study of 17.7 years (interquartile range: 16.8-18.6) and 136 siblings. Survivors and siblings reported overall comparable levels of agreement with body image statements (all p > .05). Female survivors (all odds ratio [ORs] ≥1.7), survivors treated with haematopoietic stem cell transplantation (HSCT; all ORs ≥2.2), and survivors with ≥2 chronic health conditions (all ORs ≥1.4) reported a more negative body image. This was particularly pronounced for survivors suffering from musculoskeletal or endocrine conditions. CONCLUSION Female survivors, survivors treated with HSCT or with chronic health conditions are at risk of body image concerns during adolescence. Increased awareness among clinicians and targeted psychosocial support could mitigate such concerns

Signature of magnetic-dependent gapless odd frequency states at superconductor/ferromagnet interfaces.

The theory of superconductivity developed by Bardeen, Cooper and Schrieffer (BCS) explains the stabilization of electron pairs into a spin-singlet, even frequency, state by the formation of an energy gap within which the density of states is zero. At a superconductor interface with an inhomogeneous ferromagnet, a gapless odd frequency superconducting state is predicted, in which the Cooper pairs are in a spin-triplet state. Although indirect evidence for such a state has been obtained, the gap structure and pairing symmetry have not so far been determined. Here we report scanning tunnelling spectroscopy of Nb superconducting films proximity coupled to epitaxial Ho. These measurements reveal pronounced changes to the Nb subgap superconducting density of states on driving the Ho through a metamagnetic transition from a helical antiferromagnetic to a homogeneous ferromagnetic state for which a BCS-like gap is recovered. The results prove odd frequency spin-triplet superconductivity at superconductor/inhomogeneous magnet interfaces.Engineering and Physical Sciences Research Council (Grant ID: NanoDTC EP/G037221/1)This is the final version of the article. It first appeared from Nature Publishing Group via http://dx.doi.org/10.1038/ncomms905

Bayesian spatial modelling of childhood cancer incidence in Switzerland using exact point data: a nationwide study during 1985-2015

BACKGROUND: The aetiology of most childhood cancers is largely unknown. Spatially varying environmental factors such as traffic-related air pollution, background radiation and agricultural pesticides might contribute to the development of childhood cancer. This study is the first investigation of the spatial disease mapping of childhood cancers using exact geocodes of place of residence. METHODS: We included 5947 children diagnosed with cancer in Switzerland during 1985-2015 at 0-15 years of age from the Swiss Childhood Cancer Registry. We modelled cancer risk using log-Gaussian Cox processes and indirect standardisation to adjust for age and year of diagnosis. We examined whether the spatial variation of risk can be explained by modelled ambient air concentration of NO$_{2}$, modelled exposure to background ionising radiation, area-based socio-economic position (SEP), linguistic region, duration in years of general cancer registration in the canton or degree of urbanisation. RESULTS: For all childhood cancers combined, the posterior median relative risk (RR), compared to the national level, varied by location from 0.83 to 1.13 (min to max). Corresponding ranges were 0.96 to 1.09 for leukaemia, 0.90 to 1.13 for lymphoma, and 0.82 to 1.23 for central nervous system (CNS) tumours. The covariates considered explained 72% of the observed spatial variation for all cancers, 81% for leukaemia, 82% for lymphoma and 64% for CNS tumours. There was weak evidence of an association of CNS tumour incidence with modelled exposure to background ionising radiation (RR per SD difference 1.17; 0.98-1.40) and with SEP (1.6; 1.00-1.13). CONCLUSION: Of the investigated diagnostic groups, childhood CNS tumours showed the largest spatial variation. The selected covariates only partially explained the observed variation of CNS tumours suggesting that other environmental factors also play a role

Patient-specific planning for thermal magnetic resonance of glioblastoma multiforme

Thermal intervention is a potent sensitizer of cells to chemo- and radiotherapy in cancer treatment. Glioblastoma multiforme (GBM) is a potential clinical target, given the cancer's aggressive nature and resistance to current treatment options. This drives research into optimization algorithms for treatment planning as well as radiofrequency (RF) applicator design for treatment delivery. In this work, nine clinically realistic GBM target volumes (TVs) for thermal intervention are compared using three optimization algorithms and up to ten RF applicator designs for thermal magnetic resonance. Hyperthermia treatment planning (HTP) was successfully performed for all cases, including very small, large, and even split target volumes. Minimum requirements formulated for the metrics assessing HTP outcome were met and exceeded for all patient specific cases. Results indicate a 16 channel two row arrangement to be most promising. HTP of TVs with a small extent in the cranial–caudal direction in conjunction with a large radial extent remains challenging despite the advanced optimization algorithms used. In general, deep seated targets are favorable. Overall, our findings indicate that a one-size-fits-all RF applicator might not be the ultimate approach in hyperthermia of brain tumors. It stands to reason that modular and reconfigurable RF applicator configurations might best suit the needs of targeting individual GBM geometry

Radiofrequency applicator concepts for thermal magnetic resonance of brain tumors at 297 MHz (7.0 Tesla)

PURPOSE: Thermal intervention is a potent sensitizer of cells to chemo- and radiotherapy in cancer treatment. Glioblastoma multiforme (GBM) is a potential clinical target, given the cancer's aggressive nature and resistance to current treatment options. The annular phased array (APA) technique employing electromagnetic waves in the radiofrequency (RF) range allows for localized temperature increase in deep seated target volumes (TVs). Reports on clinical applications of the APA technique in the brain are still missing. Ultrahigh field magnetic resonance (MR) employs higher frequencies than conventional MR and has potential to provide focal temperature manipulation, high resolution imaging and noninvasive temperature monitoring using an integrated RF applicator (ThermalMR). This work examines the applicability of RF applicator concepts for ThermalMR of brain tumors at 297 MHz (7.0 Tesla). METHODS: Electromagnetic field (EMF) simulations are performed for clinically realistic data based on GBM patients. Two algorithms are used for specific RF energy absorption rate based thermal intervention planning for small and large TVs in the brain, aiming at maximum RF power deposition or RF power uniformity in the TV for 10 RF applicator designs. RESULTS: For both TVs , the power optimization outperformed the uniformity optimization. The best results for the small TV are obtained for the 16 element interleaved RF applicator using an elliptical antenna arrangement with water bolus. The two row elliptical RF applicator yielded the best result for the large TV. DISCUSSION: This work investigates the capacity of ThermalMR to achieve targeted thermal interventions in model systems resembling human brain tissue and brain tumors

Constraints on instantaneous ozone production rates and regimes during DOMINO derived using in-situ OH reactivity measurements

In this study air masses are characterized in terms of their total OH reactivity which is a robust measure of the reactive air pollutant loading . The measurements were performed during the DOMINO campaign (Diel Oxidant Mechanisms In relation to Nitrogen Oxides) held from 21/11/2008 to 08/12/2008 at the Atmospheric Sounding Station - El Arenosillo (37.1° N-6.7° W, 40 m a.s.l.). The site was frequently impacted by marine air masses (arriving at the site from the southerly sector) and air masses from the cities of Huelva (located NW of the site), Seville and Madrid (located NNE of the site). OH reactivity values showed strong wind sector dependence. North eastern continental air masses were characterized by the highest OH reactivities (average: 31.4 ± 4.5 s−1; range of average diel values: 21.3-40.5 s−1), followed by north western industrial air masses (average: 13.8 ± 4.4 s−1; range of average diel values: 7-23.4 s−1) and marine air masses (average: 6.3 ± 6.6 s−1; range of average diel values: below detection limit −21.7 s−1), respectively. The average OH reactivity for the entire campaign period was ~18 s−1 and no pronounced variation was discernible in the diel profiles with the exception of relatively high values from 09:00 to 11:00 UTC on occasions when air masses arrived from the north western and southern wind sectors. The measured OH reactivity was used to constrain both diel instantaneous ozone production potential rates and regimes. Gross ozone production rates at the site were generally limited by the availability of NOx with peak values of around 20 ppbV O3 h−1. Using the OH reactivity based approach, derived ozone production rates indicate that if NOx would no longer be the limiting factor in air masses arriving from the continental north eastern sector, peak ozone production rates could double. We suggest that the new combined approach of in-situ fast measurements of OH reactivity, nitrogen oxides and peroxy radicals for constraining instantaneous ozone production rates, could significantly improve analyses of upwind point sources and their impact on regional ozone levels

Short and Intense Tailor-Made Notched Music Training against Tinnitus: The Tinnitus Frequency Matters

Tinnitus is one of the most common diseases in industrialized countries. Here, we developed and evaluated a short-term (5 subsequent days) and intensive (6 hours/day) tailor-made notched music training (TMNMT) for patients suffering from chronic, tonal tinnitus. We evaluated (i) the TMNMT efficacy in terms of behavioral and magnetoencephalographic outcome measures for two matched patient groups with either low (≤8 kHz, N = 10) or high (>8 kHz, N = 10) tinnitus frequencies, and the (ii) persistency of the TMNMT effects over the course of a four weeks post-training phase. The results indicated that the short-term intensive TMNMT took effect in patients with tinnitus frequencies ≤8 kHz: subjective tinnitus loudness, tinnitus-related distress, and tinnitus-related auditory cortex evoked activity were significantly reduced after TMNMT completion. However, in the patients with tinnitus frequencies >8 kHz, significant changes were not observed. Interpreted in their entirety, the results also indicated that the induced changes in auditory cortex evoked neuronal activity and tinnitus loudness were not persistent, encouraging the application of the TMNMT as a longer-term training. The findings are essential in guiding the intended transfer of this neuro-scientific treatment approach into routine clinical practice

A functional genetic screen defines the AKT-induced senescence signaling network

Exquisite regulation of PI3K/AKT/mTORC1 signaling is essential for homeostatic control of cell growth, proliferation, and survival. Aberrant activation of this signaling network is an early driver of many sporadic human cancers. Paradoxically, sustained hyperactivation of the PI3K/AKT/mTORC1 pathway in nontransformed cells results in cellular senescence, which is a tumor-suppressive mechanism that must be overcome to promote malignant transformation. While oncogene-induced senescence (OIS) driven by excessive RAS/ERK signaling has been well studied, little is known about the mechanisms underpinning the AKT-induced senescence (AIS) response. Here, we utilize a combination of transcriptome and metabolic profiling to identify key signatures required to maintain AIS. We also employ a whole protein-coding genome RNAi screen for AIS escape, validating a subset of novel mediators and demonstrating their preferential specificity for AIS as compared with OIS. As proof of concept of the potential to exploit the AIS network, we show that neurofibromin 1 (NF1) is upregulated during AIS and its ability to suppress RAS/ERK signaling facilitates AIS maintenance. Furthermore, depletion of NF1 enhances transformation of p53-mutant epithelial cells expressing activated AKT, while its overexpression blocks transformation by inducing a senescent-like phenotype. Together, our findings reveal novel mechanistic insights into the control of AIS and identify putative senescence regulators that can potentially be targeted, with implications for new therapeutic options to treat PI3K/AKT/mTORC1-driven cancers.Peer reviewe

Phantom headache: pain-memory-emotion hypothesis for chronic daily headache?

The neurobiology of chronic pain, including chronic daily headache (CDH) is not completely understood. “Pain memory” hypothesis is one of the mechanisms for phantom limb pain. We reviewed the literature to delineate a relation of “pain memory” for the development of CDH. There is a direct relation of pain to memory. Patients with poor memory have less chance to develop “pain memory”, hence less possibility to develop chronic pain. Progressive memory impairment may lead to decline in headache prevalence. A similar relation of pain is also noted with emotional or psychiatric symptoms. Literature review suggests that there is marked overlap in the neural network of pain to that of memory and emotions. We speculate that pain, memory, and emotions are interrelated in triangular pattern, and each of these three is related to other two in bidirectional pattern, i.e., stimulation of one of these will stimulate other symptoms/networks and vice versa (triangular theory for chronic pain). Longstanding or recurrent noxious stimuli will strengthen this interrelation, and this may be responsible for chronicity of pain. Reduction of both chronic pain and psychological symptoms by cognitive behavioral therapy or psychological interventions further suggests a bidirectional interrelation between pain and emotion. Longitudinal studies are warranted on the prevalence of headache and other painful conditions in patients with progressive memory impairment to delineate the relation of pain to memory. Interrelation of headache to emotional symptoms should also be explored