To become part of the team-patient experiences of participating in decision-making for a new treatment (proton beam therapy).

PURPOSE: The aim of this study was to explore patients' experience of participation in the treatment decision of proton beam therapy versus conventional radiotherapy. BACKGROUND: Proton beam therapy (PBT) has become a treatment option for some cancer patients receiving radiotherapy. The decision to give PBT instead of conventional radiotherapy (CRT) needs to be carefully planned together with the patient to ensure that the degree of participation is based on individuals' preferences. There is a knowledge gap of successful approaches to support patients' participation in the decision-making process, which is particularly important when it comes to the situation of having to choose between two treatment options such as PBT and CRT, with similar expected outcomes. METHOD: We conducted a secondary analysis of qualitative data collected from interviews with patients who received PBT for their brain tumor. Transcribed verbatims from interviews with 22 patients were analyzed regarding experiences of participation in the decision-making process leading to PBT. FINDINGS: Participants experienced their participation in the decision-making process to a varying degree, and with individual preferences. Four themes emerged from data: to be a voice that matters, to get control over what will happen, being in the hand of doctors' choice, and feeling selected for treatment. CONCLUSION: A decision for treatment with PBT can be experienced as a privilege but can also cause stress as it might entail practical issues affecting everyday life in a considerable way. For the patient to have confidence in the decision-making process, patients' preferences, expectations, and experiences must be included by the healthcare team. Including the patient in the healthcare team as an equal partner by confirming the person enables and facilitates for patients' voice to be heard and reckoned with. Person-centered care building on a partnership between patients and healthcare professionals should provide the right basis for the decision-making process.

Re-irradiation in Paediatric Tumours of the Central Nervous System: National Guidelines from the Swedish Workgroup of Paediatric Radiotherapy.

There is a lack of clinical protocols for re-irradiation in paediatric central nervous system (CNS) tumours. To fill this void, the Swedish Workgroup of Paediatric Radiotherapy (SBRTG) compiled national guidelines on re-irradiation in paediatric CNS tumours (diffuse intrinsic pontine glioma, ependymoma, germinoma and medulloblastoma). These have been in clinical practice since 2019 in all paediatric radiotherapy centres in Sweden. Since the implementation, the guidelines have been complemented with a yearly review on clinical outcome and toxicities in all paediatric patients treated according to the guidelines. This article presents the Swedish national guidelines on re-irradiation in paediatric CNS tumours.

Evaluating patient reported outcomes and experiences in a novel proton beam clinic - challenges, activities, and outcomes of the ProtonCare project.

BACKGROUND: The ProtonCare Study Group (PCSG) was formed with the purpose to develop and implement a framework for evaluation of proton beam therapy (PBT) and the related care at a novel clinic (Skandionkliniken), based on patient reported data. METHOD: A logic model framework was used to describe the process of development and implementation of a structured plan for evaluation of PBT for all diagnoses based on patient reported data. After the mission for the project was determined, meetings with networks and stakeholders were facilitated by PCSG to identify assumptions, resources, challenges, activities, outputs, outcomes, and outcome indicators. RESULT: This paper presents the challenges and accomplishments PCSG made so far. We describe required resources, activities, and accomplished results. The long-term outcomes that were outlined as a result of the process are two; 1) Improved knowledge about health outcomes of patients that are considered for PBT and 2) The findings will serve as a base for clinical decisions when patients are referred for PBT. CONCLUSION: Using the logical model framework proved useful in planning and managing the ProtonCare project. As a result, the work of PCSG has so far resulted in long-lasting outcomes that creates a base for future evaluation of patients' perspective in radiotherapy treatment in general and in PBT especially. Our experiences can be useful for other research groups facing similar challenges. Continuing research on patients´ perspective is a central part in ongoing and future research. Collaboration, cooperation, and coordination between research groups/networks from different disciplines are a significant part of the work aiming to determine the more precise role of PBT in future treatment options.

Postmortem genetic testing of the ryanodine receptor 2 (RYR2) gene in a cohort of sudden unexplained death cases.

The aim of this investigation was to identify pathogenic variants of the ryanodine receptor 2 (RYR2) gene in a cohort of persons aged 0-40 years who died of sudden unexpected death syndrome (SUD), including a cohort of infants who died of sudden infant death syndrome (SIDS). We genetically screened 29 of the 105 exons of the RYR2 gene associated with catecholaminergic polymorphic ventricular tachycardia (CPVT) in 74 cases of SUD without reported structural abnormalities of the heart. Cases were selected from the case database at the Institute of Forensic Medicine, and subsequent mutational screening by DNA sequencing was performed to detect variants in DNA samples extracted from blood samples of deceased persons. A total of 7 of the examined 74 cases were heterozygous for a rare sequence variant in the RYR2 gene. We identified five novel missense variants (p.Q486H, p.D1872N, p.G2367R, p.E4213D, and p.H4579Y), one synonymous variant (p.L4767L), and one previously reported missense variant (p.G4315E). Follow-up studies were possible in family members of three probands (p.Q486H, p.D1872N, and p.H4579Y), and clinical examinations were conducted in family members of two of these probands (p.Q486H and p.H4579Y). In conclusion, we identified a higher prevalence of variants in the CPVT-associated gene RYR2 than in a previously reported cohort of SIDS (9.4% vs. 1-2%). Segregation studies show that one variant (p.H4579Y) co-segregates with CPVT and is presumed to be pathogenic.

Molecular autopsy in young sudden cardiac death victims with suspected cardiomyopathy.

The aim of this investigation was to identify and characterise pathogenic mutations in a sudden cardiac death (SCD) cohort suspected of cardiomyopathy in persons aged 0-40 years. The study material for the genetic screening of cardiomyopathies consisted of 41 cases and was selected from the case database at the Institute of Forensic Medicine. Mutational screening by DNA sequencing was performed to detect mutations in DNA samples from deceased persons suspected of suffering from hypertrophic cardiomyopathy (HCM), dilated cardiomyopathy (DCM), and arrhythmogenic right ventricle cardiomyopathy (ARVC). A total of 9 of the examined 41 cases had a rare sequence variant in the MYBPC3, MYH7, LMNA, PKP2 or TMEM43 genes, of which 4 cases (9.8%) were presumed to be pathogenic mutations. The presumed pathogenic mutations were distributed with one case of suspected HCM and DCM (MYH7; p.R442H), one case of suspected DCM (LMNA; p.R471H), and two cases of suspected ARVC (PKP2; p.R79X and LMNA; p.R644C). The presented data adds important information on the genetic elements of SCD in the young, and calls for expert pathological evaluation and molecular autopsy in the post-mortem examination of SCD victims with structural anomalies of the heart.

Spontaneous coronary artery dissection: a Western Denmark Heart Registry study.

BACKGROUND: Spontaneous coronary artery dissection (SCAD) is a rare cause of acute coronary syndrome (ACS) that associates with a high acute-phase mortality rate, whereas long-term outcome is less well described. OBJECTIVE: To describe the incidence, predictors, and prognosis of SCAD. DESIGN: Retrospective case-identification study from the Western Denmark Heart Registry and the database of the Forensic Institute at Aarhus University from 1999 through 2007. RESULTS: SCAD was documented in 22 of 32,869 (0.7 per thousand) angiograms in the angiographic registry. The SCAD incidence among cases of ACS was 22 of 11,175 (2.0 per thousand). None was seen in the forensic database. The mean age was 48.7 +/- 8.9 years (range: 37-71 years). Females constituted 17 of 22 (77%) patients and all had undergone one or more pregnancies; two cases occurred in the postpartum period. The left descending artery (LAD) was the predominant site of entry. The age distribution, prevalence of the cardiovascular risk factors, presence of coronary atherosclerosis, and entry of the dissection were comparable among genders. Treatment was percutaneous coronary intervention in 13 of 22 (59%), coronary artery bypass operation in 2 of 22 (9%), and medical treatment in 7 of 22 (32%) patients. The mean follow-up period was 3.6 +/- 2.9 years. One patient suffered from recurrent SCAD; another patient died suddenly. The MACE- (cardiac death, nonfatal myocardial infarction, and new revascularization) free survival was 81% after 24 months. CONCLUSION: SCAD is a rare disease that mainly affects younger women. Compared with earlier reports, the prognosis seems to be improved by early diagnosis and interventional treatment.

Benchmark density functional theory calculations for nanoscale conductance.

We present a set of benchmark calculations for the Kohn-Sham elastic transmission function of five representative single-molecule junctions. The transmission functions are calculated using two different density functional theory methods, namely an ultrasoft pseudopotential plane-wave code in combination with maximally localized Wannier functions and the norm-conserving pseudopotential code SIESTA which applies an atomic orbital basis set. All calculations have been converged with respect to the supercell size and the number of k|| points in the surface plane. For all systems we find that the SIESTA transmission functions converge toward the plane-wave result as the SIESTA basis is enlarged. Overall, we find that an atomic basis with double zeta and polarization is sufficient (and in some cases, even necessary) to ensure quantitative agreement with the plane-wave calculation. We observe a systematic downshift of the SIESTA transmission functions relative to the plane-wave results. The effect diminishes as the atomic orbital basis is enlarged; however, the convergence can be rather slow.

Comparative study of anchoring groups for molecular electronics: structure and conductance of Au-S-Au and Au-NH(2)-Au junctions.

The electrical properties of single-molecule junctions, consisting of an organic molecule coupled to metal electrodes, are sensitive to the detailed atomic structure of the molecule-metal contact. This, in turn, is determined by the anchoring group linking the molecule to the metal. With the aim of identifying and comparing the intrinsic properties of two commonly used anchoring groups, namely thiol and amine groups, we have calculated the atomic structure and conductance traces of different Au-S-Au and Au-NH(2)-Au nanojunctions using density functional theory (DFT). Whereas NH(2) shows a strong structural selectivity towards atop-gold configurations, S shows large variability in its bonding geometries. As a result, the conductance of the Au-NH(2)-Au junction is less sensitive to the structure of the gold contacts than the Au-S-Au junction. These findings support recent experiments which show that amine-bonded molecules exhibit more well-defined conductance properties than do thiol-bonded molecules.

Evidence for a single hydrogen molecule connected by an atomic chain.

Stable, single-molecule conducting-bridge configurations are typically identified from peak structures in a conductance histogram. In previous work on Pt with H2 at cryogenic temperatures it has been shown that a peak near 1G0 identifies a single-molecule Pt-H2-Pt bridge. The histogram shows an additional structure with lower conductance that has not been identified. Here, we show that it is likely due to a hydrogen decorated Pt chain in contact with the H2 molecular bridge.

Use of the range area in organic egg production systems: effect of climatic factors, flock size, age and artificial cover.

(1) To evaluate the effect of climate, flock size, age and artificial cover on the use of range area, a study was conducted in 1994 to 1998, involving 5 farms with a total of 37 flocks of layers kept in commercial, free-range, organic systems. Flocks were visited regularly during the production period to record the number and distribution of hens on the range. (2) On average 9% of the flock used the range area, but with large variations both within and between flocks, and this was partly influenced by climatic factors. Range use was affected by temperature, wind, precipitation, season and age, and there was a tendency for reduced numbers of hens on the range with the time of day and increasing flock size. (3) Eight flocks (including houses and range areas) were divided into 8 paired units, and the range area of one unit in each of the flocks was provided with artificial cover. There were more hens on the range when artificial cover was present and the presence of cover attracted more hens away from the area immediately outside the hen house.

Mannan-binding lectin and RSV lower respiratory tract infection leading to hospitalization in children: a case-control study from Soweto, South Africa.

Respiratory syncytial virus (RSV) is the most important microbiological cause of lower respiratory tract infection (LRTI) in infants. Mannan-binding lectin (MBL) is believed to play a major protective role in the vulnerable period in infancy where the maternal antibodies have been catabolized, and the adaptive immune system has not yet matured. Mutations in the promoter region and in exon 1 of the gene-encoding MBL result in low serum levels of MBL. MBL deficiency is the most common immunodeficiency on the African Continent with frequencies of the variant alleles up to 0.29. We investigated whether MBL deficiency has an impact on the hospitalization for LRTI caused by RSV in infants from Soweto, South Africa. The cases were ethnic black Africans identified through surveillance for RSV-LRTI at Chris Hani Baragwanath Hospital, Soweto, and the controls were sampled from four immunization clinics in the area. Fifty-five cases and 113 age- and sex-matched controls were identified. Seventy-six per cent were under 6 months of age, and 42% (n = 23) were under 3 months of age. No association was found between low levels of MBL or carriage of variant alleles and LRTI caused by RSV, odds ratio (OR) 1.00 (CI 0.99-1.03) and OR 1.24 (0.73-2.12). We did not find support for the hypothesis that MBL deficiency leads to the hospitalization for LRTI caused by RSV.

Routine vaccinations and child survival: follow up study in Guinea-Bissau, West Africa.

OBJECTIVE: To examine the association between routine childhood vaccinations and survival among infants in Guinea-Bissau. DESIGN: Follow up study. PARTICIPANTS: 15 351 women and their children born during 1990 and 1996. SETTING: Rural Guinea-Bissau. MAIN OUTCOME MEASURES: Infant mortality over six months (between age 0-6 months and 7-13 months for BCG, diphtheria, tetanus, and pertussis, and polio vaccines and between 7-13 months and 14-20 months for measles vaccine). RESULTS: Mortality was lower in the group vaccinated with any vaccine compared with those not vaccinated, the mortality ratio being 0.74 (95% confidence interval 0.53 to 1.03). After cluster, age, and other vaccines were adjusted for, BCG was associated with significantly lower mortality (0.55 (0.36 to 0.85)). However, recipients of one dose of diphtheria, tetanus, and pertussis or polio vaccines had higher mortality than children who had received none of these vaccines (1.84 (1.10 to 3.10) for diphtheria, tetanus, and pertussis). Recipients of measles vaccine had a mortality ratio of 0.48 (0.27 to 0.87). When deaths from measles were excluded from the analysis the mortality ratio was 0.51 (0.28 to 0.95). Estimates were unchanged by controls for background factors. CONCLUSIONS: These trends are unlikely to be explained exclusively by selection biases since different vaccines were associated with opposite tendencies. Measles and BCG vaccines may have beneficial effects in addition to protection against measles and tuberculosis.

Distribution of early atherosclerotic lesions in the human abdominal aorta correlates with wall shear stresses measured in vivo.

OBJECTIVES: to study the relationship between wall shear stresses measured in vivo and early atherosclerotic lesions in the abdominal aorta. MATERIALS: eight young volunteers for in vivo wall shear-stress measurements. Abdominal aortas from 10 young adults without signs or history of atherosclerotic disease were obtained by autopsy for histomorphometric measurements. METHODS: wall shear stresses were measured in the abdominal aorta above and below the renal arteries using a magnetic resonance technique with high resolution for imaging and blood velocity mapping. At identical abdominal aortic locations, intimal thickness was measured blindly using histomorphometric techniques and correlated to wall shear-stress variables using linear-regression analysis. RESULTS: intimal thickness showed a linear decrease with mean wall shear stress (r=-0.90, p<0.01) and with maximum wall shear stress (r=-0.86, p<0.01). CONCLUSIONS: intimal thickness in the normal abdominal aorta is associated with mean, maximum and oscillating wall shear stresses. These in vivo data corroborate previous in vitro studies suggesting that low and oscillating wall shear stresses are localising factors for intimal thickening and hence the early development of atherosclerosis.

Effects of temperature and histopathologic preparation on the size and morphology of atherosclerotic carotid arteries as imaged by MRI.

Using magnetic resonance imaging the effects of temperature, formalin fixation, and decalcification on the size and morphology of atherosclerotic arteries were evaluated. Ten ex vivo carotid arteries were scanned fresh at body and room temperature and formalin-fixed and decalcified at room temperature. Different spin-echo pulse sequences were used and absolute T2 values calculated. During processing for histopathology, the contrast between the arterial layers increased. From body to room temperature there were significant increases in size (4%-7%), T2 of media (60--> 68 msec), and fibrous plaque component (95--> 110 msec). Formalin fixation caused significant increases in size (2%-3%) and media T2 (68--> 74 msec). Decalcification caused significant shrinkage (2%-5%) and decrease in T2 of media (74--> 53 msec) and fibrous plaque component (118--> 76 msec). Thus temperature and preparation have profound effects on contrast, size, and T2 of atherosclerotic arteries. Ex vivo experiments should be performed on fresh specimens at body temperature. J. Magn. Reson. Imaging 1999;10:876-885.

A histomorphometric method for evaluating topographic differences in degree of early atherosclerosis within the human aorta.

The aim of the study was to develop an unbiased topographically oriented method of evaluating early atherosclerotic lesions in the aorta and to apply this to a series of human aortas from young adults. A systematic sampling procedure and histomorphometric analysis of intimal thickening is described. Results from a group of 15 young adults (aged 18-40 years) showed a characteristic pattern with increasing intimal thickening when moving distally from the thoracic to the upper and finally to the lower abdominal aorta, but also a shift in the localization of the most pronounced intimal thickening from the posterior to the anterior and back to the posterior aspect. This pattern was found in aortas both with minimal and with more pronounced atherosclerosis, and supports the view that the early intimal thickening precedes the atherosclerotic lesions and marks the sites of predilection for the more advanced disease processes. An increase in intimal thickness with age could be demonstrated in the aortas without overt atherosclerosis. The simple sampling procedure, well-defined sampling sites, and ability to demonstrate and quantitate differences in intimal thickening and plaque morphology make this method well suited for relating morphometric data to other parameters of interest when studying the etiology and dynamics of atherosclerotic disease.

Prevalence of cannabinoids in urine samples from forensic autopsies.

Urine samples from 393 forensic autopsies were tested for the presence of cannabinoids by means of the radio-immunoassay test kit from DPC, Los Angeles. Fifteen per cent were found positive, mainly men and young adults. Use of cannabis was found to be closely related to drug addiction, and thus in cannabis-positive drug addicts, non-natural manners and causes of death dominate. In non-addicts the prevalence of cannabis use was 7.5%, and in non-addicted cannabis users, manners and causes of death were not very different from those found in cannabis-negatives.

Volumetric and dosimetric evaluation of radiation treatment plans: radiation conformity index.

PURPOSE: The use of conformal radiation therapy has grown substantially during the last years since three-dimensional (3D) treatment planning systems with beams-eye-view planning has become commercially available. We studied the degree of conformity reached in clinical routines for some common diagnoses treated at our department by calculating a radiation conformity index (RCI). METHODS AND MATERIALS: The radiation conformity index, determined as the ratio between the target volume (PTV) and the irradiated volume, has been evaluated for 57 patients treated with 3D treatment plans. RESULTS AND CONCLUSION: The RCI was found to vary from 0.3 to 0.6 (average 0.4), a surprisingly low figure. The higher RCI is typical for pelvic treatments (e.g., prostate) and stereotactic treatments. The lower RCI is found for extended tumors, such as mammary carcinomas where the adjacent nodes are included. The latter is also valid for most lung cancer patients studied. The RCI gives a consistent method for quantifying the degree of conformity based on isodose surfaces and volumes. Care during interpretation of RCI must always be taken, since small changes in the minimum dose can dramatically change the treated volume.

Circadian variation in bone resorption is not related to serum cortisol.

Serum osteocalcin, serum procollagen type I carboxyterminal propeptide (sPICP), and the urinary excretion of pyridinium crosslinks (biochemical markers of bone formation and resorption) all exhibit a circadian variation with a peak during the night. This study was performed to investigate the influence of the endogenous circadian rhythm in cortisol on the biochemical markers of bone turnover. Participants included 11 patients substituted with hydrocortisone due to either hypopituitarism (n = 7) or bilateral adrenalectomy (n = 4). Their daily tablet intake of hydrocortisone was divided in four equal doses in order to abrogate the known circadian variation in cortisol. 24 healthy postmenopausal women served as controls. The study design was performed over 24 h, with blood samples taken every 3 h, and urine collected in 3 h aliquots. Urinary pyridinium crosslinks (Pyr/ Cr, D-Pyr/Cr), serum osteocalcin (sOC), and serum PICP were measured. Patients without a circadian variation in cortisol had normal circadian variation in the urinary excretion of pyridinium crosslinks and sPICP, but no circadian rhythm in serum osteocalcin. We conclude that the etiology of the circadian rhythm in the biochemical markers of bone turnover is still unknown. This study indicates that the circadian variation in sOC can be controlled by the endogenous circadian variation in serum cortisol, whereas this hormone does not control the circadian variation in either the serum PICP or the urinary excretion in pyridinium crosslinks.