Retinocytoma Undergoing Retinoblastoma Transformation in an Adult Patient.

We report a 46-year-old male patient with retinocytoma who presented at the age of 31 asymptomatically. An intraocular retinal mass was incidentally found in his right eye, when he underwent ophthalmological assessment for refractive surgery. This tumor consisted of a calcified sessile basis partially covered by a pedunculated salmon-pink growth. Initially, the tumor was diagnosed as a retinocytoma with clinical suspicion of malignant transformation into retinoblastoma and treated by four sessions of laser photocoagulation. Six and a half years later, the tumor relapsed, and he was treated with a Ruthenium plaque. Following brachytherapy, he had two episodes of right-sided vitreous hemorrhage that spontaneously cleared up, and the remaining finding in the vitreous cavity was interpreted as asteroid hyalosis. He underwent vitrectomy about five years following brachytherapy. The analysis of the vitreous material revealed the presence of inactive vitreous seeds composed of small round blue cells, compatible with a type 2 regression.

Machine learning-based immune phenotypes correlate with STK11/KEAP1 co-mutations and prognosis in resectable NSCLC: a sub-study of the TNM-I trial.

BACKGROUND: We aim to implement an immune cell score model in routine clinical practice for resected non-small-cell lung cancer (NSCLC) patients (NCT03299478). Molecular and genomic features associated with immune phenotypes in NSCLC have not been explored in detail. PATIENTS AND METHODS: We developed a machine learning (ML)-based model to classify tumors into one of three categories: inflamed, altered, and desert, based on the spatial distribution of CD8+ T cells in two prospective (n = 453; TNM-I trial) and retrospective (n = 481) stage I-IIIA NSCLC surgical cohorts. NanoString assays and targeted gene panel sequencing were used to evaluate the association of gene expression and mutations with immune phenotypes. RESULTS: Among the total of 934 patients, 24.4% of tumors were classified as inflamed, 51.3% as altered, and 24.3% as desert. There were significant associations between ML-derived immune phenotypes and adaptive immunity gene expression signatures. We identified a strong association of the nuclear factor-κB pathway and CD8+ T-cell exclusion through a positive enrichment in the desert phenotype. KEAP1 [odds ratio (OR) 0.27, Q = 0.02] and STK11 (OR 0.39, Q = 0.04) were significantly co-mutated in non-inflamed lung adenocarcinoma (LUAD) compared to the inflamed phenotype. In the retrospective cohort, the inflamed phenotype was an independent prognostic factor for prolonged disease-specific survival and time to recurrence (hazard ratio 0.61, P = 0.01 and 0.65, P = 0.02, respectively). CONCLUSIONS: ML-based immune phenotyping by spatial distribution of T cells in resected NSCLC is able to identify patients at greater risk of disease recurrence after surgical resection. LUADs with concurrent KEAP1 and STK11 mutations are enriched for altered and desert immune phenotypes.

Psychometric Properties of the Norwegian Version of the Fear of COVID-19 Scale.

To examine the psychometric properties of the Norwegian version of the Fear of COVID-19 Scale (FCV-19S), randomly selected individuals from a larger registry study were invited. We assessed the reliability and validity of the instrument in a sample of 1089 adults in Norway (response rate 73%). Internal consistency measured by Cronbach's alpha (0.88) was acceptable. Omega alphaHierarchical (ωt = 0.69) was lower indicating that the general factor is less reliable, explaining 69% of the total variance. Confirmatory factor analysis indicated that the FCV-19S is not strictly unidimensional. Exploratory graph analysis and confirmatory factor analysis supported a two-factor model (cognitive and somatic fear), which were highly correlated (r = 0.84). The Norwegian version of the FCV-19S showed an underlying two-factor structure. However, the high correlation means the two latent factors (cognitive and somatic fear) act as indicators for a second-order general factor and support use of the FCV-19S sum score. The FCV-19S appears to be a valid instrument to assess fear of COVID-19 with good psychometric properties. Supplementary Information: The online version contains supplementary material available at 10.1007/s11469-020-00454-2.

Impact of KRAS, BRAF and microsatellite instability status after cytoreductive surgery and HIPEC in a national cohort of colorectal peritoneal metastasis patients.

BACKGROUND: Patients with metastatic colorectal cancer (mCRC) carrying BRAF (mutBRAF) or KRAS mutation (mutKRAS) have an inferior prognosis after liver or lung surgery, whereas the prognostic role in the context of peritoneal metastasis (PM) after cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) has been less investigated. METHODS: In total, 257 patients with non-appendiceal PM-CRC were included from the Norwegian National Unit for CRS-HIPEC. RESULTS: In total, 180 patients received CRS-HIPEC with Mitomycin C, 77 patients received palliative surgery only. In the CRS-HIPEC group, mutBRAF was found in 24.7%, mutKRAS 33.9% and double wild-type 41.4% without differences in survival. MSI was found in 29.3% of mutBRAF cases. Patients with mutBRAF/MSI had superior 5-year survival compared to mutBRAF with MSS (58.3% vs 25.2%, P = 0.022), and better 3-year disease-free survival (DFS) compared to mutKRAS (48.6% vs 17.2%, P = 0.049). Peritoneal Cancer Index and the number of lymph node metastasis were prognostic for OS, and the same two, location and gender prognostic for DFS in multivariate analysis. CONCLUSIONS: PM-CRC with CRS-HIPEC patients has a surprisingly high proportion of mutBRAF (24.7%). Survival was similar comparing mutBRAF, mutKRAS and double wild-type cases, whereas a small subgroup with mutBRAF and MSI had better survival. Patients with mutBRAF tumours and limited PM should be considered for CRS-HIPEC.

Quality of life and fear of COVID-19 in 2600 baccalaureate nursing students at five universities: a cross-sectional study.

BACKGROUND: The COVID-19 pandemic has caused significant disruptions in the implementation of programs across educational institutions. Nursing students, being both young adults and by practical training, part of the health care system, may be particularly vulnerable during the COVID-19 pandemic. The purpose of this study was to explore the associations between self-reported fear of COVID-19, general health, psychological distress and overall quality of life (QoL) in a sample of Norwegian baccalaureate nursing students compared to reference data. METHODS: The survey targeted baccalaureate nursing students from five universities in February 2021. An electronic questionnaire consisted of the Fear of COVID-19 Scale (FCV-19S), the Hopkins Symptom Checklist 5 (SCL-5), one general health and one overall QoL question. The respondents' mean scores were compared to reference data. Hierarchical regression analyses were conducted, and effect sizes (Cohen's d) were evaluated. RESULTS: In total, 2605 out of 6088 (43%) students responded. Their FCV-19S scores (mean 2.45, CI 2.42, 2.48) were significantly higher than those of the reference population (mean 1.8, P < 0.001). Nursing students scores showed significantly lower general health (mean 3.50 ± 0.93 SD, population mean = 3.57, Cohen's d = 0.07), higher levels of psychological distress (mean 2.68 ± 1.03 SD, population mean = 2.12, Cohen's d = 0.55) and lower overall QoL (mean 5.50 ± 2.16 SD, population mean = 8.00, Cohen's d = 1.16) compared to pre-pandemic reference data. FCV-19S scores were significantly associated with levels of general health (Cohen's d = 0.26), psychological distress (Cohen's d = 0.76) and overall QoL (Cohen's d = 0.18). CONCLUSIONS: Baccalaureate nursing students reported worse outcomes during the Covid-19 pandemic on general health, psychological distress and overall QoL compared to the reference population. Level of fear of Covid-19, however, accounted for few of these differences. Other factors related to the pandemic may have reduced nursing students' overall QoL.

Higher levels of bodily pain in people with long-term type 1 diabetes: associations with quality of life, depressive symptoms, fatigue and glycaemic control - the Dialong study.

AIMS: To compare reported level of bodily pain, overall and health-related quality of life (QoL), depression and fatigue in people with long-term type 1 diabetes vs. a comparison group without diabetes. Further, to examine the associations of total bodily pain with QoL, depression, fatigue and glycaemic control in the diabetes group. METHODS: Cross-sectional study of 104 (76% of eligible) people with type 1 diabetes of ≥ 45 years' duration attending the Norwegian Diabetes Centre and 75 persons without diabetes who completed questionnaires measuring bodily pain (RAND-36 bodily pain domain), shoulder pain (Shoulder Pain and Disability Index), hand pain (Australian/Canadian Osteoarthritis Hand Index), overall QoL (World Health Organization Quality of Life - BREF), health-related QoL (RAND-36), diabetes-specific QoL (Audit of Diabetes-Dependent Quality of Life; only diabetes group), depression (Patient Health Questionnaire) and fatigue (Fatigue questionnaire). For people with type 1 diabetes, possible associations between the bodily pain domain (lower scores indicate higher levels of bodily pain) and other questionnaire scores, were measured with regression coefficients (B) per 10-unit increase in bodily pain score from linear regression. RESULTS: The diabetes group reported higher levels of bodily (P = 0.003), shoulder and hand pain (P < 0.001) than the comparison group. In the diabetes group, bodily pain was associated with lower overall and diabetes-specific QoL [B (95% confidence intervals)]: 0.2 (0.1, 0.2) and 0.2 (0.1, 0.3); higher levels of depression -1.0 (-1.3, -0.7) and total fatigue -1.5 (-1.9, -1.2); and worse glycaemic control HbA1c (mmol/mol; %) -0.8 (-1.5, -0.1); -0.1 (-0.1, -0.01). CONCLUSIONS: People with long-term type 1 diabetes experience a high level of bodily pain compared with a comparison group. Total bodily pain was associated with worse QoL and glycaemic control.

How 25 years of psychosocial research has contributed to a better understanding of the links between depression and diabetes.

This narrative review of the literature provides a summary and discussion of 25 years of research into the complex links between depression and diabetes. Systematic reviews have shown that depression occurs more frequently in people with type 1 or type 2 diabetes compared with people without diabetes. Currently, it remains unclear whether depression is also more common in people with impaired glucose metabolism or undiagnosed type 2 diabetes compared with people without diabetes. More prospective epidemiological research into the course of depression and an exploration of mechanisms in individuals with diabetes are needed. Depression in diabetes is associated with less optimal self-care behaviours, suboptimal glycaemic control, impaired quality of life, incident micro- and macrovascular diseases, and elevated mortality rates. Randomized controlled trails concluded that depression in diabetes can be treated with antidepressant medication, cognitive-behavioural therapy (individual, group-based or web-based), mindfulness-based cognitive therapy and stepped care. Although big strides forward have been made in the past 25 years, scientific evidence about depression in diabetes remains incomplete. Future studies should investigate mechanisms that link both conditions and test new diabetes-specific web- or app-based interventions for depression in diabetes. It is important to determine whether treatment or prevention of depression prevents future diabetes complications and lowers mortality rates.

Integrative and comparative genomic analyses identify clinically relevant pulmonary carcinoid groups and unveil the supra-carcinoids.

The worldwide incidence of pulmonary carcinoids is increasing, but little is known about their molecular characteristics. Through machine learning and multi-omics factor analysis, we compare and contrast the genomic profiles of 116 pulmonary carcinoids (including 35 atypical), 75 large-cell neuroendocrine carcinomas (LCNEC), and 66 small-cell lung cancers. Here we report that the integrative analyses on 257 lung neuroendocrine neoplasms stratify atypical carcinoids into two prognostic groups with a 10-year overall survival of 88% and 27%, respectively. We identify therapeutically relevant molecular groups of pulmonary carcinoids, suggesting DLL3 and the immune system as candidate therapeutic targets; we confirm the value of OTP expression levels for the prognosis and diagnosis of these diseases, and we unveil the group of supra-carcinoids. This group comprises samples with carcinoid-like morphology yet the molecular and clinical features of the deadly LCNEC, further supporting the previously proposed molecular link between the low- and high-grade lung neuroendocrine neoplasms.

Longitudinal associations between depression and diabetes complications: a systematic review and meta-analysis.

To conduct a systematic review and meta-analysis of longitudinal studies assessing the bi-directional association between depression and diabetes macrovascular and microvascular complications. Embase, Medline and PsycINFO databases were searched from inception through 27 November 2017. A total of 4592 abstracts were screened for eligibility. Meta-analyses used multilevel random/mixed-effects models. Quality was assessed using the Newcastle-Ottawa scale. Twenty-two studies were included in the systematic review. Sixteen studies examined the relationship between baseline depression and incident diabetes complications, of which nine studies involving over one million participants were suitable for meta-analysis. Depression was associated with an increased risk of incident macrovascular (HR = 1.38; 95% CI: 1.30-1.47) and microvascular disease (HR = 1.33; 95% CI: 1.25-1.41). Six studies examined the association between baseline diabetes complications and subsequent depression, of which two studies involving over 230 000 participants were suitable for meta-analysis. The results showed that diabetes complications increased the risk of incident depressive disorder (HR = 1.14; 95% CI: 1.07-1.21). The quality analysis showed increased risk of bias notably in the representativeness of selected cohorts and ascertainment of exposure and outcome. Depression in people with diabetes is associated with an increased risk of incident macrovascular and microvascular complications. The relationship between depression and diabetes complications appears bi-directional. However, the risk of developing diabetes complications in depressed people is higher than the risk of developing depression in people with diabetes complications. The underlying mechanisms warrant further research.

Sound abnormally stimulates the vestibular system in canal dehiscence syndrome by generating pathological fluid-mechanical waves.

Individuals suffering from Tullio phenomena experience dizziness, vertigo, and reflexive eye movements (nystagmus) when exposed to seemingly benign acoustic stimuli. The most common cause is a defect in the bone enclosing the vestibular semicircular canals of the inner ear. Surgical repair often corrects the problem, but the precise mechanisms underlying Tullio phenomenon are not known. In the present work we quantified the phenomenon in an animal model of the condition by recording fluid motion in the semicircular canals and neural activity evoked by auditory-frequency stimulation. Results demonstrate short-latency phase-locked afferent neural responses, slowly developing sustained changes in neural discharge rate, and nonlinear fluid pumping in the affected semicircular canal. Experimental data compare favorably to predictions of a nonlinear computational model. Results identify the biophysical origin of Tullio phenomenon in pathological sound-evoked fluid-mechanical waves in the inner ear. Sound energy entering the inner ear at the oval window excites fluid motion at the location of the defect, giving rise to traveling waves that subsequently excite mechano-electrical transduction in the vestibular sensory organs by vibration and nonlinear fluid pumping.

Cytomegalovirus (CMV) Disease Despite Weekly Preemptive CMV Strategy for Recipients of Solid Organ and Hematopoietic Stem Cell Transplantation.

BACKGROUND: Transplant recipients presenting with cytomegalovirus (CMV) disease at the time of diagnosis of CMV DNAemia pose a challenge to a preemptive CMV management strategy. However, the rate and risk factors of such failure remain uncertain. METHODS: Solid organ transplantation (SOT) and hematopoietic stem cell transplantation (HSCT) recipients with a first episode of CMV polymerase chain reaction (PCR) DNAemia within the first year posttransplantation were evaluated (n = 335). Patient records were reviewed for presence of CMV disease at the time of CMV DNAemia diagnosis. The distribution and prevalence of CMV disease were estimated, and the odds ratio (OR) of CMV disease was modeled using logistic regression. RESULTS: The prevalence of CMV disease increased for both SOT and HSCT with increasing diagnostic CMV PCR load and with screening intervals >14 days. The only independent risk factor in multivariate analysis was increasing CMV DNAemia load of the diagnostic CMV PCR (OR = 6.16; 95% confidence interval, 2.09-18.11). Among recipients receiving weekly screening (n = 147), 16 (10.8%) had CMV disease at the time of diagnosis of CMV DNAemia (median DNAemia load 628 IU/mL; interquartile range, 432-1274); 93.8% of these cases were HSCT and lung transplant recipients. CONCLUSIONS: Despite application of weekly screening intervals, HSCT and lung transplant recipients in particular presented with CMV disease at the time of diagnosis of CMV DNAemia. Additional research to improve the management of patients at risk of presenting with CMV disease at low levels of CMV DNAemia and despite weekly screening is warranted.

Resveratrol displays anti-inflammatory properties in an ex vivo model of immune mediated inflammatory arthritis.

BACKGROUND: Resveratrol is a natural polyphenol found in berries, roots and wine that is well known to have anti-inflammatory and anti-oxidative properties. The anti-inflammatory effect has been reported for both immune cells and connective tissues, but only few studies have investigated effects on immune mediated inflammatory arthritis. None of which have studied this effect when combining resveratrol with methotrexate or adalimumab, two major drugs in the treatment of immune mediated inflammatory arthritis.We therefore aimed to investigate the anti-inflammatory effect of resveratrol alone and in combination with methotrexate or adalimumab in ex vivo models of immune mediated inflammatory arthritis. We furthermore aimed to describe any variations in this effect based on disease activity and cellular composition of the synovial fluid infiltrate. METHODS: Synovial fluid mononuclear cells from patients with rheumatoid arthritis (n = 7) and spondyloarthritis (n = 7) were cultured for either 48 h or 21 days. In both models, synovial fluid mononuclear cells were treated with resveratrol alone or in combination with methotrexate or adalimumab. Monocyte chemoattractant protein 1, matrix metalloproteinase 3 and tartrate resistant acidic phosphatase were measured to quantify inflammation, enzymatic degradation and osteoclast differentiation, respectively. RESULTS: Resveratrol reduced monocyte chemoattractant protein 1 production by synovial fluid mononuclear cells significantly (p = 0.005) compared to untreated controls. The effect of resveratrol was greatest in cultures from patients with low disease activity, i.e. DAS28CRP ≤ 3.2 (p = 0.022), and in cultures dominated by lymphocytes (p = 0.03). Further, the combination of methotrexate and resveratrol significantly reduced monocyte chemoattractant protein 1 levels compared with methotrexate alone in cultures from patients with low disease activity (p = 0.016), and in cultures with high lymphocyte count (p = 0.011). Resveratrol did not significantly affect matrix metalloproteinase 3 and tartrate resistant acidic phosphatase production. CONCLUSION: Resveratrol has anti-inflammatory properties in our ex vivo model of immune mediated inflammatory arthritis. Results show an additive effect of resveratrol, when combined with methotrexate in samples dominated by lymphocytes and samples from patients with low disease activity. This suggests further investigations in vitro and whether this effect may also be present in a clinical setting.

Donor Smoking and Older Age Increases Morbidity and Mortality After Lung Transplantation.

BACKGROUND: The lack of lung transplant donors has necessitated the use of donors with a smoking history and donors of older age. We have evaluated the effects of donor smoking history and age on recipient morbidity and mortality with baseline values of pulmonary function and survival free of chronic lung allograft dysfunction (CLAD) as morbidity variables. METHODS: This is a retrospective analysis of 588 consecutive lung transplant recipients and their corresponding 454 donors. Donors were divided into three groups: group 1 included smokers, group 2 nonsmokers, and group 3 had unknown smoking status; these were further divided into three age groups: group A: 0 to 39 years; group B: 40 to 54 years; and group C: ≥55 years. RESULTS: One hundred fifty-one donors were former or actual smokers, 175 were nonsmokers, and 128 had unknown smoking histories. Baseline forced expiratory volume in 1 second, forced vital capacity, and diffusion capacity of carbon monoxide were lowest in the groups who received lungs from a smoking donor. CLAD-free survival was identical in all smoking groups, and overall survival was better both for lungs from nonsmoking donors and donors with unknown smoking status compared to lungs from smoking donors. One hundred sixty-nine donors were in age group A, 203 in B, and 82 in C. Baseline forced expiratory volume in 1 second, forced vital capacity, and diffusion capacity of carbon monoxide were lowest in the groups who received lungs from donors older than 55 years. Overall survival as well as CLAD-free survival was significantly lower with donors ≥55 years. CONCLUSIONS: Donor smoking history and older donor age impact lung function, mortality, and CLAD-free survival after transplantation. Because of a shortage of organs, extended donor criteria may be considered while taking waiting list mortality into account.

Low-intensity ultrasound activates vestibular otolith organs through acoustic radiation force.

The present study examined the efficacy of 5 MHz low-intensity focused ultrasound (LiFU) as a stimulus to remotely activate inner ear vestibular otolith organs. The otolith organs are the primary sensory apparati responsible for detecting orientation of the head relative to gravity and linear acceleration in three-dimensional space. These organs also respond to loud sounds and vibration of the temporal bone. The oyster toadfish, Opsanus tau, was used to facilitate unobstructed acoustic access to the otolith organs in vivo. Single-unit responses to amplitude-modulated LiFU were recorded in afferent neurons identified as innervating the utricle or the saccule. Neural responses were equivalent to direct mechanical stimulation, and arose from the nonlinear acoustic radiation force acting on the otolithic mass. The magnitude of the acoustic radiation force acting on the otolith was measured ex vivo. Results demonstrate that LiFU stimuli can be tuned to mimic directional forces occurring naturally during physiological movements of the head, loud air conducted sound, or bone conducted vibration.

Heritability of the backtest response in piglets and its genetic correlations with production traits.

The backtest response of a pig gives an indication of its coping style, that is, its preferred strategy to cope with stressful situations, which may in turn be related to production traits. The objective of this study was therefore to estimate the heritability of the backtest response and estimate genetic correlations with production traits (birth weight, growth, fat depth and loin depth). The backtest was performed by placing the piglet on its back for 60 s and the number of struggles (NrS) and vocalizations (NrV), and the latency to struggle and vocalize (LV) was recorded. In total, 992 piglets were subjected to the backtest. Heritability estimates for backtest traits were statistically moderate (although high for behavioral traits), with LV having the highest heritability estimate (0.56±0.10, P<0.001) and NrS having the lowest estimate (0.37±0.09, P<0.001). Backtest traits also had high genetic correlations with each other, with vocalization traits (NrV and LV) having the highest (-0.94±0.03, P<0.001), and NrS with NrV the lowest correlation (0.70±0.09, P<0.001). No significant correlations were found between backtest traits and production traits, but correlations between NrS and birth weight (-0.38±0.25), and NrV and loin depth (-0.28±0.19) approached significance (P=0.07). More research into genotype-by-environment interactions may be needed to assess possible connections between backtest traits and production traits, as this may depend on the circumstances (environment, experiences, etc.). In conclusion, heritability estimates of backtest traits are high and it would therefore be possible to select for them. The high genetic correlations between backtest traits indicate that it may be possible to only consider one or two traits for characterization and selection purposes. There were no significant genetic correlations found between backtest traits and production traits, although some of the correlations approached significance and hence warrant further research.

The clinical utility of FDG PET/CT among solid organ transplant recipients suspected of malignancy or infection.

PURPOSE: Solid organ transplant (SOT) recipients are at high risk of developing infections and malignancies. 18F-FDG PET/CT may enable timely detection of these diseases and help to ensure early intervention. We aimed to describe the clinical utility of FDG PET/CT in consecutive, diagnostic unresolved SOT recipients transplanted from January 2004 to May 2015. METHODS: Recipients with a post-transplant FDG PET/CT performed as part of diagnostic work-up were included. Detailed chart reviews were done to extract relevant clinical information and determine the final diagnosis related to the FDG PET/CT. Based on á priori defined criteria and the final diagnosis, results from each scan were classified as true or false, and diagnostic values determined. RESULTS: Among the 1,814 recipients in the cohort, 145 had an FDG PET/CT performed; 122 under the indication of diagnostically unresolved symptoms with a suspicion of malignancy or infection. The remaining (N = 23) had an FDG PET/CT to follow-up on a known disease or to stage a known malignancy. The 122 recipients underwent a total of 133 FDG PET/CT scans performed for a suspected malignancy (66 %) or an infection (34 %). Sensitivity, specificity, and positive and negative predictive values of the FDG PET/CT in diagnosing these conditions were 97, 84, 87, and 96 %, respectively. CONCLUSION: FDG PET/CT is an accurate diagnostic tool for the work-up of diagnostic unresolved SOT recipients suspected of malignancy or infection. The high sensitivity and NPV underlines the potential usefulness of PET/CT for excluding malignancy or focal infections in this often complex clinical situation.

Including crossbred pigs in the genomic relationship matrix through utilization of both linkage disequilibrium and linkage analysis.

In pig breeding, the final product is a crossbred (CB) animal, while selection is performed at the purebred (PB) level using mainly PB data. However, incorporating CB data in genetic evaluations is expected to result in greater genetic progress at the CB level. Currently, there is no optimal way to include CB genotypes into the genomic relationship matrix. This is because, in single-step genomic BLUP, which is the most commonly used method, genomic and pedigree relationships must refer to the same base. This may not be the case when several breeds and CB are included. An alternative to overcome this issue may be to use a genomic relationship matrix (G matrix) that accounts for both linkage disequilibrium (LD) and linkage analysis (LA), called G. The objectives of this study were to further develop the G matrix approach to utilize both PB and CB genotypes simultaneously, to investigate its performance, and the general added value of including CB genotypes in genomic evaluations. Data were available on Dutch Landrace, Large White, and the F1 cross of those breeds. In total, 7 different G matrix compositions (PB alone, PB together, each PB with the CB, all genotypes across breeds, and G) were tested on 3 maternal traits: total number born (TNB), live born (LB), and gestation length (GL). Results show that G gave the greatest prediction accuracy of all the relationship matrices tested for PB prediction, but not for CB prediction. Including CB genotypes in general increased prediction accuracy for all breeds. However, in some cases, these increases in prediction accuracy were not significant (at < 0.05). To conclude, CB genotypes increased prediction accuracy for some of the traits and breeds, but not for all. The G matrix had significantly greater prediction accuracy in PB than the other G matrix with both PB and CB genotypes, except in one case. While for CB, the G matrix with genotypes across all breeds gave the greatest accuracy, though this was not significantly different from G. Computation time was high for G, and research will be needed to reduce its computational costs to make it feasible for use in routine evaluations. The main conclusion is that inclusion of CB genotypes is beneficial for both PB and CB animals.

Strategies for clinical implementation of TNM-Immunoscore in resected nonsmall-cell lung cancer.

Immunoscore is a prognostic tool defined to quantify in situ immune cell infiltrates and appears highly promising as a supplement to the tumor-node-metastasis (TNM) classification of various tumors. In colorectal cancer, an international task force has initiated prospective multicenter studies aiming to implement TNM-Immunoscore (TNM-I) in a routine clinical setting. In breast cancer, recommendations for the evaluation of tumor-infiltrating lymphocytes (TILs) have been proposed by an international working group. Regardless of promising results, there are potential obstacles related to implementing TNM-I into the clinic. Diverse methods may be needed for different malignancies and even within each cancer entity. Nevertheless, a uniform approach across malignancies would be advantageous. In nonsmall-cell lung cancer (NSCLC), there are several previous reports indicating an apparent prognostic importance of TILs, but studies on TILs in a TNM-I setting are sparse and no general recommendations are made. However, recently published data is promising, evoking a realistic hope of a clinical useful NSCLC TNM-I. This review will focus on the TNM-I potential in NSCLC and propose strategies for clinical implementation of a TNM-I in resected NSCLC.

Clinical Application of Variation in Replication Kinetics During Episodes of Post-transplant Cytomegalovirus Infections.

BACKGROUND: Cytomegalovirus (CMV) infection in transplant recipients is reported to replicate with a doubling time of 1.2-2 days, and weekly screening is recommended for early diagnosis. We re-evaluated these features in our cohort of transplant recipients. METHODS: The CMV doubling time of the first CMV infection in the first year post-transplant could be calculated for 193 recipients of haematopoietic stem cell or solid organ transplantation. Factors determining the proportion of recipients with a high diagnostic CMV viral load (≥ 18,200 IU/mL) were explored using mathematical simulation. FINDINGS: The overall median doubling time was 4.3 days (IQR 2.5-7.8) and was not influenced by prior CMV immunity, or type of transplantation (p > 0.4). Assuming a fixed doubling time of 1.3 days and screening intervals of 7 or 10 days, 11.1% and 33.3% were projected to have a high CMV viral load at diagnosis, compared to 1.4% and 4.3% if the doubling time varies as observed in our cohort. Consistently, 1.9% of recipients screened weekly had a high diagnostic virus load. INTERPRETATION: Screening intervals can be extended to 10 days in cohorts with comparable CMV doubling time, whereas shorter than 7 days is required in cohorts with shorter doubling times to maintain pre-emptive screening quality.

Anxiety, depression and timing of insulin treatment among people with type 2 diabetes: Nine-year follow-up of the Nord-Trøndelag Health Study, Norway.

BACKGROUND: Depression and anxiety have been found to be predictors of poor health outcomes in diabetes, but mechanisms are still unclear. AIMS: To examine whether symptoms of anxiety and depression were associated with timing of initiating insulin therapy. METHODS: A cohort study of insulin-naive particpants with type 2 dabetes completed the Hospital Anxiey and Depression Scale, HADS-A (n = 731) and/or the HADS-D (n = 768) in the communy-based Nord-Trøndelag Health Study (1995-1997). Information on insulin initiation was retrieved from the Norwegian Prescription Database from January 1, 2004 to November 21, 2012. Cox regression analyses were used to estimate the association between symptoms of anxiety, depression and time to insulin initiation. RESULTS: At baseline, 19% reported anxiety symptoms (score≥8) and 18% depressive symptoms (score≥8). After a mean follow-up of 4.4 (SD 3.6) years, 337 (40%) participants had started insulin therapy. After adjustment for sociodemographic and clinical variables, anxiety symptoms were associated with later initiation of insulin therapy (HR 0.70, 95% CI 0.49-0.99), while depressive symptoms were not. Considering groups simultaneously, having both elevated depressive and elevated anxiety symptoms was associated with later time to insulin initiation (HR 0.62, 95% CI 0.39-0.99), while having only anxiety symptoms (without depressive) HR 0.81, 95% CI 0.50-1.32) or only depressive symptoms (without anxiety) (HR 1.08, 95% CI 0.68-1.72) were not. CONCLUSIONS: Anxiety was associated with a later initiation of insulin, while depressive symptoms were not. Persons with both elevated levels of anxiety and depression were also less likely to start insulin therapy. These results need further testing in other prospective studies.