Childhood loneliness as a predictor of adolescent depressive symptoms: an 8-year longitudinal study

Childhood loneliness is characterised by children’s perceived dissatisfaction with aspects of their social relationships. This 8-year prospective study investigates whether loneliness in childhood predicts depressive symptoms in adolescence, controlling for early childhood indicators of emotional problems and a sociometric measure of peer social preference. 296 children were tested in the infant years of primary school (T1 5 years of age), in the upper primary school (T2 9 years of age) and in secondary school (T3 13 years of age). At T1, children completed the loneliness assessment and sociometric interview. Their teachers completed externalisation and internalisation rating scales for each child. At T2, children completed a loneliness assessment, a measure of depressive symptoms, and the sociometric interview. At T3, children completed the depressive symptom assessment. An SEM analysis showed that depressive symptoms in early adolescence (age 13) were predicted by reports of depressive symptoms at age 8, which were themselves predicted by internalisation in the infant school (5 years). The interactive effect of loneliness at 5 and 9, indicative of prolonged loneliness in childhood, also predicted depressive symptoms at age 13. Parent and peer-related loneliness at age 5 and 9, peer acceptance variables, and duration of parent loneliness did not predict depression. Our results suggest that enduring peer-related loneliness during childhood constitutes an interpersonal stressor that predisposes children to adolescent depressive symptoms. Possible mediators are discussed

Nucleocytoplasmic transport: a thermodynamic mechanism

The nuclear pore supports molecular communication between cytoplasm and nucleus in eukaryotic cells. Selective transport of proteins is mediated by soluble receptors, whose regulation by the small GTPase Ran leads to cargo accumulation in, or depletion from the nucleus, i.e., nuclear import or nuclear export. We consider the operation of this transport system by a combined analytical and experimental approach. Provocative predictions of a simple model were tested using cell-free nuclei reconstituted in Xenopus egg extract, a system well suited to quantitative studies. We found that accumulation capacity is limited, so that introduction of one import cargo leads to egress of another. Clearly, the pore per se does not determine transport directionality. Moreover, different cargo reach a similar ratio of nuclear to cytoplasmic concentration in steady-state. The model shows that this ratio should in fact be independent of the receptor-cargo affinity, though kinetics may be strongly influenced. Numerical conservation of the system components highlights a conflict between the observations and the popular concept of transport cycles. We suggest that chemical partitioning provides a framework to understand the capacity to generate concentration gradients by equilibration of the receptor-cargo intermediary.Comment: in press at HFSP Journal, vol 3 16 text pages, 1 table, 4 figures, plus Supplementary Material include

Tuning fulleride electronic structure and molecular ordering via variable layer index

C60 fullerides are uniquely flexible molecular materials that exhibit a rich variety of behavior, including superconductivity and magnetism in bulk compounds, novel electronic and orientational phases in thin films, and quantum transport in a single-C60 transistor. The complexity of fulleride properties stems from the existence of many competing interactions, such as electron-electron correlations, electron-vibration coupling, and intermolecular hopping. The exact role of each interaction is controversial due to the difficulty of experimentally isolating the effects of a single interaction in the intricate fulleride materials. Here we report a unique level of control of the material properties of KxC60 ultra-thin films through well-controlled atomic layer indexing and accurate doping concentrations. Using STM techniques, we observe a series of electronic and structural phase transitions as the fullerides evolve from two-dimensional monolayers to quasi-threedimensional multilayers in the early stages of layer-by-layer growth. These results demonstrate the systematic evolution of fulleride electronic structure and molecular ordering with variable KxC60 film layer index, and shed new light on creating novel molecular structures and devices.Comment: 16 pages, 4 figures, to appear in Nature Material

Polymorphism of the Tryptophan Hydroxylase 2 (TPH2) Gene Is Associated with Chimpanzee Neuroticism

In the brain, serotonin production is controlled by tryptophan hydroxylase 2 (TPH2), a genotype. Previous studies found that mutations on the TPH2 locus in humans were associated with depression and studies of mice and studies of rhesus macaques have shown that the TPH2 locus was involved with aggressive behavior. We previously reported a functional single nucleotide polymorphism (SNP) in the form of an amino acid substitution, Q468R, in the chimpanzee TPH2 gene coding region. In the present study we tested whether this SNP was associated with neuroticism in captive and wild-born chimpanzees living in Japan and Guinea, respectively. Even after correcting for multiple tests (Bonferroni p = 0.05/6 = 0.008), Q468R was significantly related to higher neuroticism (β = 0.372, p = 0.005). This study is the first to identify a genotype linked to a personality trait in chimpanzees. In light of the prior studies on humans, mice, and rhesus macaques, these findings suggest that the relationship between neuroticism and TPH2 has deep phylogenetic roots

Combined treatment of adenoid cystic carcinoma with cetuximab and IMRT plus C12 heavy ion boost: ACCEPT [ACC, Erbitux® and particle therapy]

<p>Abstract</p> <p>Background</p> <p>Local control in adjuvant/definitive RT of adenoid cystic carcinoma (ACC) is largely dose-dependent leading to the establishment of particle therapy in this indication. However, even modern techniques leave space for improvement of local control by intensification of local treatment. Radiation sensitization by exploitation of high EGFR-expression in ACC with the EGFR receptor antibody cetuximab seems promising.</p> <p>Methods/design</p> <p>The ACCEPT trial is a prospective, mono-centric, phase I/II trial evaluating toxicity (primary endpoint: acute and late effects) and efficacy (secondary endpoint: local control, distant control, disease-free survival, overall survival) of the combined treatment with IMRT/carbon ion boost and weekly cetuximab in 49 patients with histologically proven (≥R1-resected, inoperable or Pn+) ACC. Patients receive 18 GyE carbon ions (6 fractions) and 54 Gy IMRT (2.0 Gy/fraction) in combination with weekly cetuximab throughout radiotherapy.</p> <p>Discussion</p> <p>The primary objective of ACCEPT is to evaluate toxicity and feasibility of cetuximab and particle therapy in adenoid cystic carcinoma.</p> <p>Trial Registration</p> <p>Clinical Trial Identifier: <a href="http://www.clinicaltrials.gov/ct2/show/NCT01192087">NCT 01192087</a></p> <p>EudraCT number: 2010 - 022425 - 15</p

Raster-scanned carbon ion therapy for malignant salivary gland tumors: acute toxicity and initial treatment response

<p>Abstract</p> <p>Background and purpose</p> <p>To investigate toxicity and efficacy in high-risk malignant salivary gland tumors (MSGT) of the head and neck. Local control in R2-resected adenoid cystic carcinoma was already improved with a combination of IMRT and carbon ion boost at only mild side-effects, hence this treatment was also offered to patients with MSGT and microscopic residual disease (R1) or perineural spread (Pn+).</p> <p>Methods</p> <p>From November 2009, all patients with MSGT treated with carbon ion therapy were evaluated. Acute side effects were scored according to CTCAE v.4.03. Tumor response was assessed according to RECIST where applicable.</p> <p>Results</p> <p>103 patients were treated from 11/2009 to 03/2011, median follow-up is 6 months. 60 pts received treatment following R2 resections or as definitive radiation, 43 patients received adjuvant radiation for R1 and/or Pn+. 16 patients received carbon ion treatment for re-irradiation. Median total dose was 73.2 GyE (23.9 GyE carbon ions + 49,9 Gy IMRT) for primary treatment and 44.9 GyE carbon ions for re-irradiation. All treatments were completed as planned and generally well tolerated with no > CTC°III toxicity. Rates of CTC°III toxicity (mucositis and dysphagia) were 8.7% with side-effects almost completely resolved at first follow-up.</p> <p>47 patients showed good treatment responses (CR/PR) according to RECIST.</p> <p>Conclusion</p> <p>Acute toxicity remains low in IMRT with carbon ion boost also in R1-resected patients and patients undergoing re-irradiation. R2-resected patients showed high rates of treatment response, though follow-up is too short to assess long-term disease control.</p

Effects of phone versus mail survey methods on the measurement of health-related quality of life and emotional and behavioural problems in adolescents

<p>Abstract</p> <p>Background</p> <p>Telephone interviews have become established as an alternative to traditional mail surveys for collecting epidemiological data in public health research. However, the use of telephone and mail surveys raises the question of to what extent the results of different data collection methods deviate from one another. We therefore set out to study possible differences in using telephone and mail survey methods to measure health-related quality of life and emotional and behavioural problems in children and adolescents.</p> <p>Methods</p> <p>A total of 1700 German children aged 8-18 years and their parents were interviewed randomly either by telephone or by mail. Health-related Quality of Life (HRQoL) and mental health problems (MHP) were assessed using the KINDL-R Quality of Life instrument and the Strengths and Difficulties Questionnaire (SDQ) children's self-report and parent proxy report versions. Mean Differences ("d" effect size) and differences in Cronbach alpha were examined across modes of administration. Pearson correlation between children's and parents' scores was calculated within a multi-trait-multi-method (MTMM) analysis and compared across survey modes using Fisher-Z transformation.</p> <p>Results</p> <p>Telephone and mail survey methods resulted in similar completion rates and similar socio-demographic and socio-economic makeups of the samples. Telephone methods resulted in more positive self- and parent proxy reports of children's HRQoL (SMD ≤ 0.27) and MHP (SMD ≤ 0.32) on many scales. For the phone administered KINDL, lower Cronbach alpha values (self/proxy Total: 0.79/0.84) were observed (mail survey self/proxy Total: 0.84/0.87). KINDL MTMM results were weaker for the phone surveys: mono-trait-multi-method mean r = 0.31 (mail: r = 0.45); multi-trait-mono-method mean (self/parents) r = 0.29/0.36 (mail: r = 0.34/0.40); multi-trait-multi-method mean r = 0.14 (mail: r = 0.21). Weaker MTMM results were also observed for the phone administered SDQ: mono-trait-multi-method mean r = 0.32 (mail: r = 0.40); multi-trait-mono-method mean (self/parents) r = 0.24/0.30 (mail: r = 0.20/0.32); multi-trait-multi-method mean r = 0.14 (mail = 0.14). The SDQ classification into borderline and abnormal for some scales was affected by the method (OR = 0.36-1.55).</p> <p>Conclusions</p> <p>The observed differences between phone and mail surveys are small but should be regarded as relevant in certain settings. Therefore, while both methods are valid, some changes are necessary. The weaker reliability and MTMM validity associated with phone methods necessitates improved phone adaptations of paper and pencil questionnaires. The effects of phone versus mail survey modes are partly different across constructs/measures.</p

How Abnormal Is the Behaviour of Captive, Zoo-Living Chimpanzees?

Background. Many captive chimpanzees (Pan troglodytes) show a variety of serious behavioural abnormalities, some of which have been considered as possible signs of compromised mental health. The provision of environmental enrichments aimed at reducing the performance of abnormal behaviours is increasing the norm, with the housing of individuals in (semi-)natural social groups thought to be the most successful of these. Only a few quantitative studies of abnormal behaviour have been conducted, however, particularly for the captive population held in zoological collections. Consequently, a clear picture of the level of abnormal behaviour in zoo-living chimpanzees is lacking. Methods. We present preliminary findings from a detailed observational study of the behaviour of 40 socially-housed zoo-living chimpanzees from six collections in the United States of America and the United Kingdom. We determined the prevalence, diversity, frequency, and duration of abnormal behaviour from 1200 hours of continuous behavioural data collected by focal animal sampling. Results, conclusion, and significance. Our overall finding was that abnormal behaviour was present in all sampled individuals across six independent groups of zoo-living chimpanzees, despite the differences between these groups in size, composition, housing, etc. We found substantial variation between individuals in the frequency and duration of abnormal behaviour, but all individuals engaged in at least some abnormal behaviour and variation across individuals could not be explained by sex, age, rearing history or background (defined as prior housing conditions). Our data support a conclusion that, while most behaviour of zoo-living chimpanzees is ‘normal’ in that it is typical of their wild counterparts, abnormal behaviour is endemic in this population despite enrichment efforts. We suggest there is an urgent need to understand how the chimpanzee mind copes with captivity, an issue with both scientific and welfare implications