A meta-analysis of cambium phenology and growth: linear and non-linear patterns in conifers of the northern hemisphere

Background and Aims Ongoing global warming has been implicated in shifting phenological patterns such as the timing and duration of the growing season across a wide variety of ecosystems. Linear models are routinely used to extrapolate these observed shifts in phenology into the future and to estimate changes in associated ecosystem properties such as net primary productivity. Yet, in nature, linear relationships may be special cases. Biological processes frequently follow more complex, non-linear patterns according to limiting factors that generate shifts and discontinuities, or contain thresholds beyond which responses change abruptly. This study investigates to what extent cambium phenology is associated with xylem growth and differentiation across conifer species of the northern hemisphere. Methods Xylem cell production is compared with the periods of cambial activity and cell differentiation assessed on a weekly time scale on histological sections of cambium and wood tissue collected from the stems of nine species in Canada and Europe over 1–9 years per site from 1998 to 2011. Key Results The dynamics of xylogenesis were surprisingly homogeneous among conifer species, although dispersions from the average were obviously observed. Within the range analysed, the relationships between the phenological timings were linear, with several slopes showing values close to or not statistically different from 1. The relationships between the phenological timings and cell production were distinctly non-linear, and involved an exponential pattern. Conclusions The trees adjust their phenological timings according to linear patterns. Thus, shifts of one phenological phase are associated with synchronous and comparable shifts of the successive phases. However, small increases in the duration of xylogenesis could correspond to a substantial increase in cell production. The findings suggest that the length of the growing season and the resulting amount of growth could respond differently to changes in environmental conditions.

Initial cord blood unit volume affects mononuclear cell and CD34+ cell-processing efficiency in a non-linear fashion

Umbilical cord blood (UCB) is a source of hematopoietic stem cells that initially was used exclusively for the hematopoietic reconstitution of pediatric patients. It is now suggested for use for adults as well, a fact that increases the pressure to obtain units with high cellularity. Therefore, the optimization of UCB processing is a priority.

An integrative transcranial magnetic stimulation mapping technique using non-linear curve fitting

The aim of this study is to develop a new simple method for analyzing one-dimensional transcranial magnetic stimulation (TMS) mapping studies in humans. Motor evoked potentials (MEP) were recorded from the abductor pollicis brevis (APB) muscle during stimulation at nine different positions on the scalp along a line passing through the APB hot spot and the vertex. Non-linear curve fitting according to the Levenberg-Marquardt algorithm was performed on the averaged amplitude values obtained at all points to find the best-fitting symmetrical and asymmetrical peak functions. Several peak functions could be fitted to the experimental data. Across all subjects, a symmetric, bell-shaped curve, the complementary error function (erfc) gave the best results. This function is characterized by three parameters giving its amplitude, position, and width. None of the mathematical functions tested with less or more than three parameters fitted better. The amplitude and position parameters of the erfc were highly correlated with the amplitude at the hot spot and with the location of the center of gravity of the TMS curve. In conclusion, non-linear curve fitting is an accurate method for the mathematical characterization of one-dimensional TMS curves. This is the first method that provides information on amplitude, position and width simultaneously.

Short anterior correction of the thoracolumbar/lumbar curve in King 1 idiopathic scoliosis: the behaviour of the instrumented and non-instrumented curves and the trunk balance

This is a retrospective clinical, radiological and patient outcome assessment of 21 consecutive patients with King 1 idiopathic adolescent scoliosis treated by short anterior selective fusion of the major thoracolumbar/lumbar (TL/L) curve. Three-dimensional changes of both curves, changes in trunk balance and rib hump were evaluated. The minimal follow-up was 24 months (max. 83). The Cobb angle of the TL/L curve was 52 degrees (45-67 degrees) with a flexibility of 72% (40-100%). The average length of the main curve was 5 (3-8) segments. An average of 3 (2-4) segments was fused using rigid single rod implants with side-loading screws. The Cobb angle of the thoracic curve was 33 degrees (18-50 degrees) with a flexibility of 69% (29-100%). The thoracic curve in bending was less than 20 degrees in 17 patients, and 20-25 degrees in 4 patients. In the TL/L curve there was an improvement of the Cobb angle of 67%, of the apex vertebral rotation of 51% and of the apex vertebral translation of 74%. The Cobb angle of the thoracic curve improved 29% spontaneously. Shoulder balance improved significantly from an average preoperative imbalance of 14.5-3.1 mm at the last follow-up. Seventy-five percent of the patients with preoperative positive shoulder imbalance (higher on the side of the thoracic curve) had levelled shoulders at the last follow-up. C7 offset improved from a preoperative 19.8 (0-40) to 4.8 (0-18) mm at the last follow-up. There were no significant changes in rotation, translation of the thoracic curve and the clinical rib hump. There were no significant changes in thoracic kyphosis or lumbar lordosis. The average score of the SRS-24 questionnaire at the last follow-up was 91 points (max. 120). We conclude that short anterior selective fusion of the TL/L curve in King 1 scoliosis with a thoracic curve bending to 25 degrees or less (Type 5 according to Lenke classification) results in a satisfactory correction and a balanced spine. Short fusions leave enough mobile lumbar segments for the establishment of global spinal balance. A positive shoulder imbalance is not a contraindication for this procedure. Structural interbody grafts are not necessary to maintain lumbar lordosis.

Image registration for triggered and non-triggered DTI of the human kidney: Reduced variability of diffusion parameter estimation

BACKGROUND: To investigate if non-rigid image-registration reduces motion artifacts in triggered and non-triggered diffusion tensor imaging (DTI) of native kidneys. A secondary aim was to determine, if improvements through registration allow for omitting respiratory-triggering. METHODS: Twenty volunteers underwent coronal DTI of the kidneys with nine b-values (10-700 s/mm2 ) at 3 Tesla. Image-registration was performed using a multimodal nonrigid registration algorithm. Data processing yielded the apparent diffusion coefficient (ADC), the contribution of perfusion (FP ), and the fractional anisotropy (FA). For comparison of the data stability, the root mean square error (RMSE) of the fitting and the standard deviations within the regions of interest (SDROI ) were evaluated. RESULTS: RMSEs decreased significantly after registration for triggered and also for non-triggered scans (P < 0.05). SDROI for ADC, FA, and FP were significantly lower after registration in both medulla and cortex of triggered scans (P < 0.01). Similarly the SDROI of FA and FP decreased significantly in non-triggered scans after registration (P < 0.05). RMSEs were significantly lower in triggered than in non-triggered scans, both with and without registration (P < 0.05). CONCLUSION: Respiratory motion correction by registration of individual echo-planar images leads to clearly reduced signal variations in renal DTI for both triggered and particularly non-triggered scans. Secondarily, the results suggest that respiratory-triggering still seems advantageous.J. Magn. Reson. Imaging 2014. (c) 2014 Wiley Periodicals, Inc.

EGFR inhibitors erlotinib and lapatinib ameliorate epidermal blistering in pemphigus vulgaris in a non-linear, V-shaped relationship.

Novel insights into intra-cellular signalling involved in pemphigus vulgaris (PV), an autoimmune blistering disease of skin and mucous membranes, are now revealing new therapeutic approaches such as the chemical inhibition of PV-associated signals in conjunction with standard immunosuppressive therapy. However, extensive inhibition of signalling molecules that are required for normal tissue function and integrity may hamper this approach. Using a neonatal PV mouse model, we demonstrate that epidermal blistering can be prevented in a dose-dependent manner by clinically approved EGFR inhibitors erlotinib and lapatinib, but only up to approximately 50% of normal EGFR activity. At lower EGFR activity, blisters again aggravated and were highly exacerbated in mice with a conditional deletion of EGFR. Statistical analysis of the relation between EGFR activity and the extent of skin blistering revealed the best fit with a non-linear, V-shaped curve with a median break point at 52% EGFR activity (P = 0.0005). Moreover, lapatinib (a dual EGFR/ErbB2 inhibitor) but not erlotinib significantly reduced blistering in the oral cavity, suggesting that signalling mechanisms differ between PV predilection sites. Our results demonstrate that future clinical trials evaluating EGFR/ErbB2 inhibitors in PV patients must select treatment doses that retain a specific level of signal molecule activity. These findings may also be of relevance for cancer patients treated with EGFR inhibitors, for whom skin lesions due to extensive EGFR inhibition represent a major threat.

Religion and assisted and non-assisted suicide in Switzerland: National Cohort Study

Background In the 19th century, eminent French sociologist Emile Durkheim found suicide rates to be higher in the Protestant compared with the Catholic cantons of Switzerland. We examined religious affiliation and suicide in modern Switzerland, where assisted suicide is legal. Methods The 2000 census records of 1 722 456 (46.0%) Catholics, 1 565 452 (41.8%) Protestants and 454 397 (12.2%) individuals with no affiliation were linked to mortality records up to December 2005. The association between religious affiliation and suicide, with the Protestant faith serving as the reference category, was examined in Cox regression models. Hazard ratios (HRs) with 95% confidence intervals (CIs) were adjusted for age, marital status, education, type of household, language and degree of urbanization. Results Suicide rates per 100 000 inhabitants were 19.7 in Catholics (1664 suicides), 28.5 in Protestants (2158 suicides) and 39.0 in those with no affiliation (882 suicides). Associations with religion were modified by age and gender (P < 0.0001). Compared with Protestant men aged 35–64 years, HRs (95% CI) for all suicides were 0.80 (0.73–0.88) in Catholic men and 1.09 (0.98–1.22) in men with no affiliation; and 0.60 (0.53–0.67) and 1.96 (1.69–2.27), respectively, in men aged 65–94 years. Corresponding HRs in women aged 35–64 years were 0.90 (0.80–1.03) and 1.46 (1.25–1.72); and 0.67 (0.59–0.77) and 2.63 (2.22–3.12) in women aged 65–94 years. The association was strongest for suicides by poisoning in the 65–94-year-old age group, the majority of which was assisted: HRs were 0.45 (0.35–0.59) for Catholic men and 3.01 (2.37–3.82) for men with no affiliation; 0.44 (0.36–0.55) for Catholic women and 3.14 (2.51–3.94) for women with no affiliation. Conclusions In Switzerland, the protective effect of a religious affiliation appears to be stronger in Catholics than in Protestants, stronger in older than in younger people, stronger in women than in men, and particularly strong for assisted suicides.

Reproducibility and day time bias correction of optoelectronic leg volumetry: a prospective cohort study

Background Leg edema is a common manifestation of various underlying pathologies. Reliable measurement tools are required to quantify edema and monitor therapeutic interventions. Aim of the present work was to investigate the reproducibility of optoelectronic leg volumetry over 3 weeks' time period and to eliminate daytime related within-individual variability. Methods Optoelectronic leg volumetry was performed in 63 hairdressers (mean age 45 ± 16 years, 85.7% female) in standing position twice within a minute for each leg and repeated after 3 weeks. Both lower leg (legBD) and whole limb (limbBF) volumetry were analysed. Reproducibility was expressed as analytical and within-individual coefficients of variance (CVA, CVW), and as intra-class correlation coefficients (ICC). Results A total of 492 leg volume measurements were analysed. Both legBD and limbBF volumetry were highly reproducible with CVA of 0.5% and 0.7%, respectively. Within-individual reproducibility of legBD and limbBF volumetry over a three weeks' period was high (CVW 1.3% for both; ICC 0.99 for both). At both visits, the second measurement revealed a significantly higher volume compared to the first measurement with a mean increase of 7.3 ml ± 14.1 (0.33% ± 0.58%) for legBD and 30.1 ml ± 48.5 ml (0.52% ± 0.79%) for limbBF volume. A significant linear correlation between absolute and relative leg volume differences and the difference of exact day time of measurement between the two study visits was found (P < .001). A therefore determined time-correction formula permitted further improvement of CVW. Conclusions Leg volume changes can be reliably assessed by optoelectronic leg volumetry at a single time point and over a 3 weeks' time period. However, volumetry results are biased by orthostatic and daytime-related volume changes. The bias for day-time related volume changes can be minimized by a time-correction formula.

Publication and non-publication of clinical trials: longitudinal study of applications submitted to a research ethics committee

BACKGROUND: Not all clinical trials are published, which may distort the evidence that is available in the literature. We studied the publication rate of a cohort of clinical trials and identified factors associated with publication and nonpublication of results. METHODS: We analysed the protocols of randomized clinical trials of drug interventions submitted to the research ethics committee of University Hospital (Inselspital) Bern, Switzerland from 1988 to 1998. We identified full articles published up to 2006 by searching the Cochrane CENTRAL database (issue 02/2006) and by contacting investigators. We analyzed factors associated with the publication of trials using descriptive statistics and logistic regression models. RESULTS: 451 study protocols and 375 corresponding articles were analyzed. 233 protocols resulted in at least one publication, a publication rate of 52%. A total of 366 (81%) trials were commercially funded, 47 (10%) had non-commercial funding. 346 trials (77%) were multi-centre studies and 272 of these (79%) were international collaborations. In the adjusted logistic regression model non-commercial funding (Odds Ratio [OR] 2.42, 95% CI 1.14-5.17), multi-centre status (OR 2.09, 95% CI 1.03-4.24), international collaboration (OR 1.87, 95% CI 0.99-3.55) and a sample size above the median of 236 participants (OR 2.04, 95% CI 1.23-3.39) were associated with full publication. CONCLUSIONS: In this cohort of applications to an ethics committee in Switzerland, only about half of clinical drug trials were published. Large multi-centre trials with non-commercial funding were more likely to be published than other trials, but most trials were funded by industry.