Facilitating clinically relevant skin tumor diagnostics with spectroscopy-driven machine learning.

In the dawning era of artificial intelligence (AI), health care stands to undergo a significant transformation with the increasing digitalization of patient data. Digital imaging, in particular, will serve as an important platform for AI to aid decision making and diagnostics. A growing number of studies demonstrate the potential of automatic pre-surgical skin tumor delineation, which could have tremendous impact on clinical practice. However, current methods rely on having ground truth images in which tumor borders are already identified, which is not clinically possible. We report a novel approach where hyperspectral images provide spectra from small regions representing healthy tissue and tumor, which are used to generate prediction maps using artificial neural networks (ANNs), after which a segmentation algorithm automatically identifies the tumor borders. This circumvents the need for ground truth images, since an ANN model is trained with data from each individual patient, representing a more clinically relevant approach.

BioMEL: a translational research biobank of melanocytic lesions and melanoma.

INTRODUCTION: Diagnosing invasive cutaneous melanoma (CM) can be challenging due to subjectivity in distinguishing equivocal nevi, melanoma in situ and thin CMs. The underlying molecular mechanisms of progression from nevus to melanoma must be better understood. Identifying biomarkers for treatment response, diagnostics and prognostics is crucial. Using biomedical data from biobanks and population-based healthcare data, translational research can improve patient care by implementing evidence-based findings. The BioMEL biobank is a prospective, multicentre, large-scale biomedical database on equivocal nevi and all stages of primary melanoma to metastases. Its purpose is to serve as a translational resource, enabling researchers to uncover objective molecular, genotypic, phenotypic and structural differences in nevi and all stages of melanoma. The main objective is to leverage BioMEL to significantly improve diagnostics, prognostics and therapy outcomes of patients with melanoma. METHODS AND ANALYSIS: The BioMEL biobank contains biological samples, epidemiological information and medical data from adult patients who receive routine care for melanoma. BioMEL is focused on primary and metastatic melanoma, but equivocal pigmented lesions such as clinically atypical nevi and melanoma in situ are also included. BioMEL data are gathered by questionnaires, blood sampling, tumour imaging, tissue sampling, medical records and histopathological reports. ETHICS AND DISSEMINATION: The BioMEL biobank project is approved by the national Swedish Ethical Review Authority (Dnr. 2013/101, 2013/339, 2020/00469, 2021/01432 and 2022/02421-02). The datasets generated are not publicly available due to regulations related to the ethical review authority. TRIAL REGISTRATION NUMBER: NCT05446155.

A Non-Interventional Study on Vismodegib for Basal Cell Carcinoma in Swedish Patients.

INTRODUCTION: Real-life data on vismodegib in advanced basal cell carcinoma (aBCC) are limited. Optimal treatment duration is left to the discretion of the physician. OBJECTIVES: To assess the effectiveness, safety and treatment pattern for vismodegib in aBCC in clinical practice. METHODS: In this multicenter, non-interventional, prospective study, 49 Swedish patients planned for vismodegib treatment were included. The treatment pattern observed was treatment until remission, allowing unlimited discontinuations/pauses. RESULTS: The majority of patients (93.8%), discontinued at least once during the study. Compared to earlier studies there was a decrease of more than 2 months with actual drug intake, reducing the patients burden and costs, at the same time as a high number of responses were seen (87.8%). Median progression-free-survival was 16.7 months, and 90% of the patients were alive at 13.3 months. Ten patients were re-challenged with vismodegib at recurrence or progression, resulting in five partial remissions and three complete remissions. CONCLUSIONS: Clinical response rates with vismodegib for aBCC were comparable to those of similar trials despite a shorter and more intermittent treatment duration. The majority of re-challenges lead to partial or complete remissions.

Comparison of photoacoustic imaging and histopathological examination in determining the dimensions of 52 human melanomas and nevi ex vivo.

Surgical excision followed by histopathological examination is the gold standard for the diagnosis and staging of melanoma. Reoperations and unnecessary removal of healthy tissue could be reduced if non-invasive imaging techniques were available for presurgical tumor delineation. However, no technique has gained widespread clinical use to date due to shallow imaging depth or the absence of functional imaging capability. Photoacoustic (PA) imaging is a novel technology that combines the strengths of optical and ultrasound imaging to reveal the molecular composition of tissue at high resolution. Encouraging results have been obtained from previous animal and human studies on melanoma, but there is still a lack of clinical data. This is the largest study of its kind to date, including 52 melanomas and nevi. 3D multiwavelength PA scanning was performed ex vivo, using 59 excitation wavelengths from 680 nm to 970 nm. Spectral unmixing over this broad wavelength range, accounting for the absorption of several tissue chromophores, provided excellent contrast between healthy tissue and tumor. Combining the results of spectral analysis with spatially resolved information provided a map of the tumor borders in greater detail than previously reported. The tumor dimensions determined with PA imaging were strongly correlated with those determined by histopathological examination for both melanomas and nevi.

Genotype-Environment Correlation and Its Relation to Personality - A Twin and Family Study.

The aim of the study was to examine the Family and School Psychosocial Environment (FSPE) questionnaire in relation to a possible genotype-environment correlation and genetic mediation between the FSPE variables and personality variables, assessed by the Junior Eysenck Personality Questionnaire. A sample of 506 Swedish children aged 10-20 years from 253 families were recruited via the Swedish state population and address register and SchoolList.Eu. The children were divided into 253 pairs: 46 monozygotic twin pairs, 42 dizygotic twin pairs, 140 pairs of full siblings and 25 pairs of half-siblings. The behavioral genetic analysis showed that both FSPE factors, Warmth and Conflicts, may be partly influenced by genetic factors (suggesting genotype-environment correlation) and that nonadditive genetic factors may mediate the relationship between FSPE factors and psychoticism/antisocial personality (P). An indication of a special shared monozygotic twin environment was found for P and Lie/social desirability, but based on prior research findings this factor may have a minor influence on P and L. P and L were negatively correlated, and the relationship seems to be partly mediated by nonadditive genetic factors. Nonshared environment and measurement errors seem to be the most influential mediating factors, but none of the cross-twin cross-dimension correlations suggest a common shared environmental mediating factor.

Photoacoustic imaging for three-dimensional visualization and delineation of basal cell carcinoma in patients.

BACKGROUND: Photoacoustic (PA) imaging is an emerging non-invasive biomedical imaging modality that could potentially be used to determine the borders of basal cell carcinomas (BCC) preoperatively in order to reduce the need for repeated surgery. METHODS: Two- and three-dimensional PA images were obtained by scanning BCCs using 59 wavelengths in the range 680-970 nm. Spectral unmixing was performed to visualize the tumor tissue distribution. Spectral signatures from 38 BCCs and healthy tissue were compared ex vivo. RESULTS AND DISCUSSION: The PA spectra could be used to differentiate between BCC and healthy tissue ex vivo (p < 0.05). Spectral unmixing provided visualization of the overall architecture of the lesion and its border. CONCLUSION: PA imaging can be used to differentiate between BCC and healthy tissue and can potentially be used to delineate tumors prior to surgical excision.

Unique spectral signature of human cutaneous squamous cell carcinoma by photoacoustic imaging.

Cutaneous squamous cell carcinoma (cSCC) is a common skin cancer with metastatic potential. To reduce reoperations due to nonradical excision, there is a need to develop a technique for identification of tumor margins preoperatively. Photoacoustic (PA) imaging is a novel imaging technology that combines the strengths of laser optics and ultrasound. Our aim was to determine the spectral signature of cSCC using PA imaging and to use this signature to visualize tumor architecture and borders. Two-dimensional PA images of 33 cSCCs and surrounding healthy skin were acquired ex vivo, using 59 excitation wavelengths from 680 to 970 nm. The spectral response of the cSCCs was compared to healthy tissue, and the difference was found to be greatest at wavelengths in the range 765 to 960 nm (P < .05). Three-dimensional PA images were constructed from spectra obtained in the y-z plane using a linear stepper motor moving along the x-plane. Spectral unmixing was then performed which provided a clear three-dimensional view of the distribution of tumor masses and their borders.

Radioecological modelling of Polonium-210 and Caesium-137 in lichen-reindeer-man and top predators.

This work deals with analysis and modelling of the radionuclides 210Pb and210Po in the food-chain lichen-reindeer-man in addition to 210Po and 137Cs in top predators. By using the methods of Partial Least Square Regression (PLSR) the atmospheric deposition of 210Pb and 210Po is predicted at the sample locations. Dynamic modelling of the activity concentration with differential equations is fitted to the sample data. Reindeer lichen consumption, gastrointestinal absorption, organ distribution and elimination is derived from information in the literature. Dynamic modelling of transfer of 210Pb and 210Po to reindeer meat, liver and bone from lichen consumption, fitted well with data from Sweden and Finland from 1966 to 1971. The activity concentration of 210Pb in the skeleton in man is modelled by using the results of studying the kinetics of lead in skeleton and blood in lead-workers after end of occupational exposure. The result of modelling 210Pb and 210Po activity in skeleton matched well with concentrations of 210Pb and 210Po in teeth from reindeer-breeders and autopsy bone samples in Finland. The results of 210Po and 137Cs in different tissues of wolf, wolverine and lynx previously published, are analysed with multivariate data processing methods such as Principal Component Analysis PCA, and modelled with the method of Projection to Latent Structures, PLS, or Partial Least Square Regression PLSR.

Cutaneous malignant melanoma show geographic and socioeconomic disparities in stage at diagnosis and excess mortality.

Background Preventive measures are needed to counteract the increasing burden of cutaneous malignant melanoma (CMM). As a basis for rational melanoma prevention, we investigated geographic differences and impact from socioeconomic factors related to incidence, clinical stage at diagnosis and outcome. Material and methods All patients with primary invasive CMM diagnosed in 2004-2013 in the southern and the western Swedish health care regions with a population of 2.9 million adults were eligible for the study. Population-based data were obtained from the national Cancer Register and the national Melanoma Quality Register. Geographic and socioeconomic differences in incidence per stage at diagnosis were mapped and correlated to excess mortality. Results Disease mapping based on 9743 cases in 99 municipalities and 20 metropolitan districts showed marked, regional disparities in stage-specific incidence of CMM. The incidence of stage I-II tumors was higher in the western health care region, whereas the incidence of stage III-IV CMMs was higher in the southern region. The divergent incidence patterns per stage at diagnosis were consistent across population strata based on educational level. The geographic disparities in CMM stage influenced relative survival with an excess five-year mortality ratio in the southern region versus the western region of 1.49 (95% confidence interval 1.22-1.82). The excess mortality ratio for patients with low versus high educational level was 1.81 (1.37-2.40). Conclusion Residential region and educational level influenced CMM stage and, thereby, excess mortality. These observations suggest that geographic as well as socioeconomic data should be considered in prevention of CMM.

Radioactivity levels in the marine environment along the Exclusive Economic Zone (EEZ) of Qatar.

A study on (137)Cs, (40)K, (226)Ra, (228)Ra, and (238)U was carried out along the EEZ of Qatar. Results serve as the first ever baseline data. The level of (137)Cs (mean value 1.6 ± 0.4 Bq m(-3)) in water filters was found to be in the same order of magnitude as reported by others in worldwide marine radioactivity studies. Results are also in agreement with values reported from other Gulf regions. The computed values of sediment-water distribution coefficients Kd, are lower than the values given by IAEA. Measurements were carried out for bottom sediments, biota samples like fish, oyster, sponge, seashell, mangrove, crab, shrimp, starfish, dugong and algae. The 'concentration factors' reported for biota samples are below the levels published by IAEA and cause no significant impact on human health for seafood consumers in Qatar.

Polonium-210 and Caesium-137 in lynx (Lynx lynx), wolverine (Gulo gulo) and wolves (Canis lupus).

Wolves, lynx and wolverines are on the top of the food-chain in northern Scandinavia and Finland. (210)Po and (137)Cs have been analysed in samples of liver, kidney and muscle from 28 wolves from Sweden. In addition blood samples were taken from 27 wolves. In 9 of the wolves, samples of muscle, liver and blood were analysed for (210)Po. Samples of liver and muscle were collected from 16 lynx and 16 wolverines from Norway. The liver samples were analysed for (210)Po and (137)Cs. Only (137)Cs analyses were carried out for the muscle samples. The wolves were collected during the winter 2010 and 2011, while the samples for lynx and wolverines were all from 2011. The activity concentrations of (210)Po in wolves were higher for liver (range 20-523 Bq kg(-1) d.w.) and kidney (range 24-942 Bq kg(-1) d.w.) than muscle (range 1-43 Bq kg(-1) d.w.) and blood (range 2-54 Bq kg(-1) d.w.). Activity ratios, (210)Po/(210)Pb, in wolf samples of muscle, liver and blood were in the ranges 2-77, 9-56 and 2-54. Using a wet weight ratio of 3.8 the maximal absorbed dose from (210)Po to wolf liver was estimated to 3500 µGy per year. Compared to wolf, the ranges of (210)Po in liver samples were lower in lynx (range 22-211 Bq kg(-1) d.w.) and wolverine (range16-160 Bq kg(-1) d.w.). Concentration of (137)Cs in wolf samples of muscle, liver, kidney and blood were in the ranges 70-8410 Bq kg(-1) d.w., 36-4050 Bq kg(-1) d.w., 31-3453 Bq kg(-1) d.w. and 4-959 Bq kg(-1) d.w., respectively. (137)Cs in lynx muscle and liver samples were in the ranges 44-13393 Bq kg(-1) d.w. and 125-10260 Bq kg(-1) d.w. The corresponding values for (137)Cs in wolverine were 22-3405 Bq kg(-1) d.w. for liver and 53-4780 Bq kg(-1) d.w. for muscle. The maximal absorbed dose from (137)Cs to lynx was estimated to 3000 µGy per year.

(7)Be, (210)Pb, and (210)Po in the surface air from the Arctic to Antarctica.

In the present study we have investigated the activity concentrations of (210)Pb, (210)Po as well as (7)Be in surface air of the North and South Atlantic (1988-1989), the Arctic Ocean (1991), and along the coastline of Siberia (1994) during succeeding expeditions in the Swedish Polar Research program. During the cruises in the Arctic Ocean during 1991-07-28 to 1991-10-04 the average air concentrations of (7)Be was 0.6 ± 0.4 mBq/m(3), (210)Pb 40 ± 4 µBq/m(3) and (210)Po-38 ± 10 µBq/m(3). During the Swedish-Russian Tundra Ecology-94 expedition along the Siberian coastline the average air concentrations of (7)Be and (210)Pb measured during May-July were 11 ± 3, and 2.4 ± 0.4 mBq/m(3), and during July-September they were 7.2 ± 2 and 2.7 ± 1.1 mBq/m(3) respectively. The results from measurements of the activity concentration of (210)Pb in the air over the Arctic Ocean vary between 75 and 176 µBq/m(3). In the air close to land masses, however, the activity concentration of (210)Pb in the air increases to 269-2712 µBq/m(3). The activity concentration of (7)Be in the South Atlantic during the cruise down to Antarctica varied between 1.3 and 1.7 with an average of 1.5 ± 0.8 mBq/m(3). The activity concentration of (210)Pb in the South Atlantic down to Antarctica varied between 6 and 14 µBq/m(3). At the Equator the activity concentration recorded in November 1988 was 630 µBq/m(3) and in April 1989 it was 260 µBq/m(3). The average activity concentration of (210)Pb during the route Gothenburg-Montevideo in 1988 was 290 and on the return Montevideo-Gothenburg it was 230 µBq/m(3). The activity concentration of (210)Po in the South Atlantic down to Antarctica varied between 15 and 58 µBq/m(3). At the Equator the activity concentration in November 1988 was 170 and in April 1989 it was 70 µBq/m(3). The average activity concentration of (210)Po during the route Gothenburg-Montevideo in 1988 was 63 and on the return Montevideo-Gothenburg it was 60 µBq/m(3). The average of the activity concentrations in the Antarctic air of (210)Pb was 27 ± 10 µBq/m(3) and of (210)Po it was 12 ± 7 µBq/m(3). All our results were compiled together with other published data, and the global latitudinal distribution of (210)Pb was converted to total annual deposition (Bq/m(2)/a) and fitted to a 4th degree polynomial. By using the global latitudinal distribution of (210)Po/(210)Pb-activity ratio from our own results the global latitudinal distribution of (210)Po annual deposition was derived.

Photon activation therapy of RG2 glioma carrying Fischer rats using stable thallium and monochromatic synchrotron radiation.

75 RG2 glioma-carrying Fischer rats were treated by photon activation therapy (PAT) with monochromatic synchrotron radiation and stable thallium. Three groups were treated with thallium in combination with radiation at different energy; immediately below and above the thallium K-edge, and at 50 keV. Three control groups were given irradiation only, thallium only, or no treatment at all. For animals receiving thallium in combination with radiation to 15 Gy at 50 keV, the median survival time was 30 days, which was 67% longer than for the untreated controls (p = 0.0020) and 36% longer than for the group treated with radiation alone (not significant). Treatment with thallium and radiation at the higher energy levels were not effective at the given absorbed dose and thallium concentration. In the groups treated at 50 keV and above the K-edge, several animals exhibited extensive and sometimes contra-lateral edema, neuronal death and frank tissue necrosis. No such marked changes were seen in the other groups. The results were discussed with reference to Monte Carlo calculated electron energy spectra and dose enhancement factors.

Calcium efflux of plasma membrane vesicles exposed to ELF magnetic fields--test of a nuclear magnetic resonance interaction model.

The question whether very weak, low frequency magnetic fields can affect biological matter is still under debate. The theoretical possibility of such an interaction is often questioned and the site of interaction in the cell is unknown. In the present study, the influence of extremely weak 60 Hz magnetic fields on the transport of Ca(2+) was studied in a biological system consisting of highly purified plasma membrane vesicles. We tested a newly proposed quantum mechanical model postulates that polarization of hydrogen nuclei can elicit a biological effect. Vesicles were exposed for half an hour at 32 °C and the calcium efflux was studied using radioactive (45) Ca(2+) as a tracer. A static magnetic field of 26 µT and time-varying magnetic fields with a frequency of 60 Hz and amplitudes between 0.6 and 6.3 µT were used. The predictions of the model, proposed by Lednev, that at a frequency of 60 Hz the biological effect under investigation would significantly be altered at the amplitudes of 1.3 and 3.9 µT could not be confirmed.

Analgetic effects of non-thermal GSM-1900 radiofrequency electromagnetic fields in the land snail Helix pomatia.

PURPOSE: To investigate whether mobile phone radiation might affect snail nociception, employing radiofrequency (RF) electromagnetic fields (EMF) which, to our knowledge, have hitherto not been studied in a snail model. Exposure to extremely low frequency (ELF) magnetic fields has however been shown to significantly affect nociceptive responses. MATERIALS AND METHODS: In the present study, we exposed 29 land snails of the strain Helix pomatia to global system for mobile communications (GSM) EMF at 1900 MHz at the non-thermal level 48 mW/kg for 1 hour each and 29 snails were sham controls. The experiments took place during the onset of summer, with all snails being well out of hibernation. Before and after GSM or sham exposure, the snails were subjected to thermal pain by being placed on a hot plate. The reaction time for retraction from the hot plate was measured by two blinded observers. RESULTS: Comparing the reaction pattern of each snail before and after exposure, the GSM-exposed snails were less sensitive to thermal pain as compared to the sham controls, indicating that RF exposure induces a significant analgesia (Mann-Whitney p < 0.001). CONCLUSION: This study might support earlier findings, describing beneficial effects of EMF exposure upon nociception.

A descriptive study of bacterial load of full-thickness surgical wounds in dermatologic surgery.

BACKGROUND: Surgical site infections (SSIs) after dermatologic surgery cause pain, prolong healing, result in unaesthetic complications, and lead to excessive use of antibiotics. The pathogenesis of wound infections is complex and is dependent on bacterial load and diversity, among several factors. OBJECTIVE: To investigate bacterial dynamics at dermatosurgical sites at different time intervals and assess the correlation with postoperative outcomes and to examine different endo- and exogenous factors that may contribute to SSIs. METHODS: Eighteen patients undergoing skin grafting of the face were studied. The following SSI-related factors were registered: age and sex of the patient, ulceration of the lesion, diabetes, immunosuppressive therapy, smoking, anticoagulative therapy, and use of antibiotic prophylaxis. Wounds from each patient were swabbed preoperatively, intraoperatively, and postoperatively. The bacterial composition of the swabs was then analyzed quantitatively and qualitatively. RESULTS: Sixteen of 18 surgical sites contained varying quantities of surface-associated bacteria. Coagulase-negative staphylococci and Propionibacterium acnes were the predominant bacteria isolated at all times. Intraoperative analysis was not predictive of SSIs. Use of antibiotic prophylaxis was the only registered SSI-related factor that showed significant variation in bacterial load between pre- and postoperative samples. Postoperative bacterial load was found to be lower than preoperative load in patients who received antibiotics. This was in contrast to patients who did not receive antibiotics, who had significantly higher postoperative levels (p=.02). The presence of high postoperative bacterial loads, regardless of the bacterial species isolated, showed a statistically significant positive correlation with a complicated postoperative outcome (p≤.001). CONCLUSIONS: This study provides novel insights into the bacterial dynamics of dermatologic surgery-induced wounds and the variation of this over time. The results highlight the potential relevance of quantifying bacterial loads, as well as determining specific types of bacteria, in dermatologic surgery.

Polonium-210 and lead-210 in the terrestrial environment: a historical review.

The radionuclides (210)Po and (210)Pb widely present in the terrestrial environment are the final long-lived radionuclides in the decay of (238)U in the earth's crust. Their presence in the atmosphere is due to the decay of (222)Rn diffusing from the ground. The range of activity concentrations in ground level air for (210)Po is 0.03-0.3 Bq m(-3) and for (210)Pb 0.2-1.5 Bq m(-3). In drinking water from private wells the activity concentration of (210)Po is in the order of 7-48 mBq l(-1) and for (210)Pb around 11-40 mBq l(-1). From water works, however, the activity concentration for both (210)Po and (210)Pb is only in the order of 3 mBq l(-1). Mosses, lichens and peat have a high efficiency in capturing (210)Po and (210)Pb from atmospheric fallout and exhibit an inventory of both (210)Po and (210)Pb in the order of 0.5-5 kBq m(-2) in mosses and in lichens around 0.6 kBq m(-2). The activity concentrations in lichens lies around 250 Bq kg(-1), dry mass. Reindeer and caribou graze lichen which results in an activity concentration of (210)Po and (210)Pb of about 1-15 Bq kg(-1) in meat from these animals. The food chain lichen-reindeer or caribou, and Man constitutes a unique model for studying the uptake and retention of (210)Po and (210)Pb in humans. The effective annual dose due to (210)Po and (210)Pb in people with high consumption of reindeer/caribou meat is estimated to be around 260 and 132 µSv a(-1) respectively. In soils, (210)Po is adsorbed to clay and organic colloids and the activity concentration varies with soil type and also correlates with the amount of atmospheric precipitation. The average activity concentration levels of (210)Po in various soils are in the range of 20-240 Bq kg(-1). Plants become contaminated with radioactive nuclides both by absorption from the soil (supported Po) and by deposition of radioactive fallout on the plants directly (unsupported Po). In fresh leafy plants the level of (210)Po is particularly high as the result of the direct deposition of (222)Rn daughters from atmospheric deposition. Tobacco is a terrestrial product with high activity concentrations of (210)Po and (210)Pb. The overall average activity concentration of (210)Po is 13 ± 2 Bq kg(-1). It is rather constant over time and by geographical origin. The average median daily dietary intakes of (210)Po and (210)Pb for the adult world population was estimated to 160 mBq day(-1) and 110 mBq day(-1), corresponding to annual effective doses of 70 µSv a(-1) and 28 µSv a(-1), respectively. The dietary intakes of (210)Po and (210)Pb from vegetarian food was estimated to only 70 mBq day(-1) and 40 mBq day(-1) corresponding to annual effective doses of 30.6 µSv a(-1) and 10 µSv a(-1), respectively. Since the activity concentration of (210)Po and (210)Pb in seafood is significantly higher than in vegetarian food the effective dose to populations consuming a lot of seafood might be 5-15 fold higher.

Family and School Psychosocial Environment (FSPE): development of a brief questionnaire measuring perceived psychosocial environments in children/siblings.

The aim of the study was to develop a short Swedish standardized, factor analyzed and cross-validated, family and school psychosocial environment questionnaire (FSPE). The study was based on 244 Swedish girls and boys, 10-19 years old, who filled in the FSPE. Maximum likelihood factor analysis, promax rotation, yielded six primary factors, based on absolute ratings. Since the factors were somewhat correlated, two broader secondary factors, with satisfactory reliabilities, were also included in the form, named Warmth, support and openness from parents, siblings and peers, and Family conflicts and school discipline, respectively. Means and standard deviations for girls and boys showed sex differences in most of the factors. Because the children participated anonymously they could report about spanking without negative consequences. Indeed, 8.1% of the children had been spanked by their parents. Based on relative ratings, two factors were identified, covering environmental questions about "more than, the same as or less than" a sibling. Only 6.6% of the children rated their environment exactly the same on the Family Psychosocial Environment (FPE) factors, compared to a sibling within the family. Thus the majority reported environmental differences. Further research is proposed to evaluate such differences and relations to personality, genotype-environment correlation and genetic mediation.