HOMEFOOD Randomised Trial - Six-Month Nutrition Therapy in Discharged Older Adults Reduces Hospital Readmissions and Length of Stay at Hospital Up to 18 Months of Follow-Up.

BACKGROUND: Malnutrition is frequently observed in older adults and is associated with hospital readmissions, length of stay (LOS), and mortality in discharged patients. OBJECTIVE: The aim of this study was to investigate effects of six-month nutrition therapy on hospital readmissions, LOS, mortality and need for long-term care residence 1-, 6-, 12- and 18-months post-discharge in older Icelandic adults. DESIGN: Secondary analysis of a randomized controlled trial. PARTICIPANTS: Participants (>65 years) were randomised into intervention (n=53) and control (n=53) before discharge from a geriatric unit. INTERVENTION: The intervention group received nutrition therapy based on the Nutrition Care Process, including home visits, phone calls, freely delivered energy- and protein-rich foods and supplements for six months after hospital discharge. MEASUREMENTS: The Icelandic electronic hospital registry was accessed to gain information on emergency room visits (ER), hospital readmissions, LOS, mortality and need for long-term care residence. RESULTS: The intervention group had a lower proportion of participants with at least one readmission compared to control (1 month: 1.9% vs 15.8%, P=0.033; 6 months: 25.0% vs 46.2%, P=0.021; 12 months: 38.5% vs 55.8%, P=0.051; and 18 months: 51.9% vs 65.4%, P=0.107). There was also a lower total number of readmissions per participant (1 month: 0.02 vs 0.19, P=0.015; 6 month: 0.33 vs 0.77, P=0.014; 0.62 vs 1.12, P=0.044) and a shorter LOS (1 month: 0.02 vs 0.92, P=0.013; 6 months: 2.44 vs 13.21; P=0.006; 12 months: 5.83 vs 19.40, P=0.034; 18 months: 10.42 vs 26.00, P=0.033) in the intervention group. However, there were no differences between groups in ER visits, mortality and need for long-term care residence. CONCLUSION: A six-month nutrition therapy in older Icelandic adults discharged from hospital reduced hospital readmissions and shortens LOS at the hospital up to 18-months post-discharge. However, it did neither affect mortality, ER, nor need of long-term care residence in this group.

Trends in renal function in Northern Sweden 1986-2014: data from the seven cross-sectional surveys within the Northern Sweden MONICA study.

OBJECTIVE: The prevalence of chronic kidney disease (CKD) is increasing globally, and CKD is closely related to cardiovascular disease (CVD). CKD and CVD share several risk factors (RF), such as diabetes, hypertension, obesity and smoking, and the prevalence of these RF has changed during the last decades, and we aimed to study the effect on renal function over time. DESIGN: Repeated cross-sectional population-based studies. SETTING: The two Northern counties (Norr- and Västerbotten) in Sweden. PARTICIPANTS: Within the MONitoring Trends and Determinants of CArdiovascular Disease (MONICA) study, seven surveys were performed between 1986 and 2014, including participants aged 25-64 years (n=10 185). INTERVENTIONS: None. MEASURES: Information on anthropometry, blood pressure and cardiovascular risk factors was collected. Creatinine and cystatin C were analysed in stored blood samples and the estimated glomerular filtration rate (eGFR) calculated using the creatinine-based Lund-Malmö revised and Chronic Kidney Disease Epidemiology Collaboration (eGFRcrea) equations as well as the cystatin C-based Caucasian, Asian, Paediatric and Adult cohort (CAPA) equation (eGFRcysC). Renal function over time was analysed using univariable and multivariable linear regression models. RESULTS: Renal function, both eGFRcrea and eGFRcysC, decreased over time (both p<0.001) and differed between counties and sexes. In a multivariable analysis, study year remained inversely associated with both eGFRcrea and eGFRcysC (both p<0.001) after adjustment for classical cardiovascular RF. CONCLUSION: Renal function has deteriorated in Northern Sweden between 1986 and 2014.

The association between self-treatment and mental health among Swedish physicians.

BACKGROUND: Despite a high prevalence of mental health problems among physicians, the rate of help-seeking behaviour is low. Instead, physicians tend to self-treat. This can have a negative impact on individual physicians and society. AIMS: The aim was to explore the relationship between self-rated depression, the use of psychotropic medication, and the extent of self-treatment across gender and hierarchical position among Swedish physicians. In addition, the aim was to investigate whether social support can buffer against self-treatment. METHODS: This study draws on data from the Longitudinal Occupational Health for Health Care in Sweden 2021 study, comprising a representative sample of physicians. Descriptive statistics and logistic regressions were carried out. RESULTS: The present study showed that approximately 60% of the physicians using narcotic or non-narcotic psychotropic medication were self-prescribing. Male and more senior physicians self-treated to a greater extent. Physicians without depression were self-treating to a greater extent than those with depression. Those who used non-narcotic psychotropic medication intermittently were more likely to self-treat than those who used these medications regularly. The frequency of use was insignificant in relation to self-treatment with narcotic psychotropic medication. No buffering effect from social support at work was found. CONCLUSIONS: Self-treatment was common among physicians in Sweden, particularly among those who reported mild or no symptoms of depression. This may have negative long-term effects on an individual level and for Swedish health care at large.

HOMEFOOD randomized trial-beneficial effects of 6-month nutrition therapy on body weight and physical function in older adults at risk for malnutrition after hospital discharge.

BACKGROUND/OBJECTIVES: Malnutrition is common among older adults. Dietary intervention studies in older adults aiming to improve anthropometrics measures and physical function have been inconsistent. We aimed to investigate the effects of nutrition therapy in combination with home delivered meals and oral nutritional supplements (ONS) in community-dwelling older adults discharged from hospital. METHODS: A total of 106 participants (>65 years) were randomized into the intervention group (n = 53) and into the control group (n = 53). The intervention group received individual nutrition therapy (five in person visits and three phone calls) and freely delivered energy- and protein- rich foods, while the control group received standard care. Dietary intake, anthropometrics, and short physical performance battery (SPPB) were assessed at baseline and at endpoint. RESULTS: Energy intake at baseline was similar in both groups (~1500 kcal at the hospital) but there was a significant increase in energy intake and body weight in the intervention group (+919 kcal/day and 1.7 kg, P < 0.001 in both cases) during the study period, compared to a significant decrease in both measures among controls (-815 kcal/day and -3.5 kg, P < 0.001 in both cases). SPPB score increased significantly in the intervention group while no changes were observed among controls. CONCLUSIONS: Most Icelandic older adults experience substantial weight loss after hospital discharge when receiving current standard care. However, a 6-month multi-component nutrition therapy, provided by a clinical nutritionist in combination with freely delivered supplemental energy- and protein-dense foods has beneficial effects on body weight, physical function, and nutritional status. STUDY REGISTRATION: This study was registered at ClinicalTrials.gov ( NCT03995303 ).

Kidney function in patients with bipolar disorder with and without lithium treatment compared with the general population in northern Sweden: results from the LiSIE and MONICA cohorts.

BACKGROUND: The clinical relevance of lithium nephropathy is subject to debate. Kidney function decreases with age and comorbidities, and this decline might lead to attribution bias when erroneously ascribed to lithium. We aimed to investigate whether patients with bipolar or schizoaffective disorder had faster decline in estimated glomerular filtration rate (eGFR) compared with the general population, whether observed differences in the steepness of the decline were attributable to lithium, and whether such changes depended on the length of lithium exposure. METHODS: In this cross-sectional cohort study, we used clinical data from the Lithium-Study into Effects and Side-effects (LiSIE) retrospective cohort study, which included patients with bipolar disorder or schizoaffective disorder whose medical records were reviewed up to Dec 31, 2017, and the WHO Monitoring of Trends and Determinants in Cardiovascular Disease (MONICA) study, covering a representative sample of the general population in northern Sweden aged 25-74 years. The primary outcome was the age-associated decline of creatinine-based eGFR, assessed using linear regression. We adjusted for sex and grouped for different lengths of lithium exposure (never or <1 year, 1-5 years, >5-10 years, and >10 years). For patients with moderate-to-severe kidney disease we identified the underlying nephropathy in the case records. FINDINGS: From LiSIE, we included 785 patients (498 [63%] female and 287 [37%] male), with a mean age of 49·8 years (SD 13·2; range 25-74). From MONICA, we included 1549 individuals (800 [52%] female and 749 [48%] male), with a mean age of 51·9 years (13·8; 25-74). No ethnicity data were collected. Adjusted for duration of lithium exposure, eGFR declined by 0·57 mL/min/1·73 m2/year (95% CI 0·50-0·63) in patients with bipolar disorder or schizoaffective disorder and by 0·57 mL/min/1·73 m2/year (0·53-0·61) in the reference population. Lithium added 0·54 mL/min/1·73 m2 (0·43-0·64) per year of treatment (p<0·0001). After more than 10 years on lithium, decline was significantly steeper than in all other groups including the reference population (p<0·0001). Lithium nephropathy was judged to be the commonest cause of moderate-to-severe chronic kidney disease, but comorbidities played a role. The effect of lithium on eGFR showed a high degree of inter-individual variation. INTERPRETATION: Steeper eGFR decline in patients with bipolar disorder or schizoaffective disorder can be attributed to lithium, but the trajectory of kidney function decline varies widely. Comorbidities affecting kidneys should be treated assertively as one possible means to affect the trajectory. In patients with a fast trajectory, a trade-off is required between continuing lithium to treat mental health problems and discontinuing lithium for the sake of renal health. FUNDING: Norrbotten County Research and Learning Fund Sweden, Visare Norr (Northern County Councils Regional Federation Fund), Swedish Kidney Foundation (Njurfonden), Swedish Kidney Association (Njurförbundet), Norrbotten section. TRANSLATION: For the Swedish translation of the Summary see Supplementary Materials section.

HOMEFOOD randomised trial - Six-month nutrition therapy improves quality of life, self-rated health, cognitive function, and depression in older adults after hospital discharge.

BACKGROUND AND AIMS: Malnutrition is common among older adults and is related to quality of life, cognitive function, and depression. To what extent nutrition interventions can improve these outcomes remains unclear. The aim of this study was to investigate the effect of nutrition therapy on health-related quality of life (EQ-5D), self-rated health, cognitive function, and depression in community dwelling older adults recently discharged from hospital. METHODS: Participants (>65 years) were randomised into an intervention (n = 53) and a control group (n = 53). The intervention group received individualised nutrition therapy based on the nutrition care process including 5 home visits and 3 phone calls, in combination with freely delivered energy- and protein-rich foods and oral nutrition supplements for six months after hospital discharge. EQ-5D, self-rated health, Mini-Mental-State-Examination (MMSE), and the Centre for Epidemiologic Studies Depression - IOWA (CES-D) scale were measured at baseline and at endpoint. RESULTS: Two subjects dropped out, one from each arm. The control group experienced an increase in depressive symptoms and a decrease in self-rated health during the study period, while the intervention group experienced increases in cognitive function, self-rated health, and EQ-5D resulting in significant endpoint differences between the groups: EQ-5D (0.102, P = 0.001); self-rated health: 15.876 (P < 0.001); MMSE: 1.701 (P < 0.001); depressive symptoms: - 3.072 (P < 0.001); all in favour of the intervention group. Improvements during the intervention in MMSE, self-rated health, and CES-D were significantly related to body weight gain in a linear way. CONCLUSION: Cognitive function and mental well-being worsen or stagnate in older adults who receive standard care after hospital discharge. However, a six-month nutrition therapy improves these outcomes leading to statistically and clinically significant endpoint differences between the groups. As improvements were related to body weight gain after hospital discharge, we conclude that the increase in dietary intake, with focus on energy and protein density, and changes in body weight might have contributed to better cognitive function and mental well-being in older adults after the intervention.

Changes in home care clients' characteristics and home care in five European countries from 2001 to 2014: comparison based on InterRAI - Home Care data.

BACKGROUND: Policymakers advocate extended residence in private homes as people age, rather than relocation to long-term care facilities. Consequently, it is expected that older people living in their own homes will be frailer and have more complex health problems over time. Therefore, community care for aging people is becoming increasingly important to facilitate prevention of decline in physical and cognitive abilities and unnecessary hospital admission and transfer to a nursing home. The aim of this study was to examine changes in the characteristic of home care clients and home care provided in five European countries between 2001 and 2014 and to explore whether home care clients who are most in need of care receive the care required. METHODS: This descriptive study used data from two European research projects, Aged in Home Care (AdHOC; 2001-2002) and Identifying best practices for care-dependent elderly by Benchmarking Costs and outcomes of Community Care (IBenC; 2014-2016). In both projects, the InterRAI-Home Care assessment tool was used to assess a random sample of home care clients 65 years and older in five European countries. These data facilitate a comparison of physical and cognitive health and the provided home care between countries and study periods. RESULTS: In most participating countries, both cognitive (measured on the Cognitive Performance Scale) and functional ability (measured on the Activities of Daily Living Hierarchy scale) of home care clients deteriorated over a 10-year period. Home care provided increased between the studies. Home care clients who scored high on the physical and cognitive scales also received home care for a significantly higher duration than those who scored low. CONCLUSION: Older people in several European countries remain living in their own homes despite deteriorating physical and cognitive skills. Home care services to this group have increased. This indicates that the government policy of long-term residence at own home among older people, even in increased frailty, has been realised.

Development of clinical competence - a longitudinal survey of nurse practitioner students.

BACKGROUND: In order to achieve a sustainable standard of advanced clinical competence for nurse practitioners leading to a credible role, it is important to investigate the development of clinical competence among nurse practitioner students. AIM: The aim of the present study is to analyse the development of nurse practitioner students' self-assessed clinical competence from the beginning of their education to after completion of their clinical studies. DESIGN: The study involved the application of a longitudinal survey design adhering to STROBE guidelines. METHODS: The participants consisted of 36 registered nurses from a nurse practitioner programme at a Norwegian university. The Professional Nurse Self-Assessment Scale II was used for data collection during the period August 2015 to May 2020. RESULTS: The students developed their clinical competence the most for direct clinical practice. Our findings are inconclusive in terms of whether the students developed clinical competence regarding consultation, coaching and guidance, and collaboration. However, they do indicate a lack of development in some aspects of clinical leadership. The students with the lowest level of clinical competence developed their clinical competence regarding direct clinical practice significantly more than the students with the highest level of clinical competence. The differences between students with high and low levels of clinical competence were levelled out during their education. Thus, the students as a whole became a more homogenous group after completion of their clinical studies. Previous work experience in primary healthcare was a statistically significant, yet minor, predictor of the development of clinical competence. CONCLUSION: Our findings indicate that the students developed their clinical competence for direct clinical practice in accordance with the intended learning outcomes of the university's Master's programme and international standards for nurse practitioners. It is imperative that the clinical field supports nurse practitioners by facilitating extended work-task fits that are appropriate to their newly developed clinical competence. We refrain from concluding with a recommendation that prior clinical work experience should be an entry requirement for nurse practitioner programmes. However, we recommend an evaluation of the nurse practitioner education programme with the aim of investigating whether the curriculum meets the academic standards of clinical leadership expected in advanced level of nursing.

The sarcopenia and physical frailty in older people: multi-component treatment strategies (SPRINTT) project: description and feasibility of a nutrition intervention in community-dwelling older Europeans.

BACKGROUND: The "Sarcopenia and Physical Frailty in Older People: Multicomponent Treatment Strategies" (SPRINTT) project sponsored a multi-center randomized controlled trial (RCT) with the objective to determine the effect of physical activity and nutrition intervention for prevention of mobility disability in community-dwelling frail older Europeans. We describe here the design and feasibility of the SPRINTT nutrition intervention, including techniques used by nutrition interventionists to identify those at risk of malnutrition and to carry out the nutrition intervention. METHODS: SPRINTT RCT recruited older adults (≥ 70 years) from 11 European countries. Eligible participants (n = 1517) had functional limitations measured with Short Physical Performance Battery (SPPB score 3-9) and low muscle mass as determined by DXA scans, but were able to walk 400 m without assistance within 15 min. Participants were followed up for up to 3 years. The nutrition intervention was carried out mainly by individual nutrition counseling. Nutrition goals included achieving a daily protein intake of 1.0-1.2 g/kg body weight, energy intake of 25-30 kcal/kg of body weight/day, and serum vitamin D concentration ≥ 75 mmol/L. Survey on the method strategies and feasibility of the nutrition intervention was sent to all nutrition interventionists of the 16 SPRINTT study sites. RESULTS: Nutrition interventionists from all study sites responded to the survey. All responders found that the SPRINTT nutrition intervention was feasible for the target population, and it was well received by the majority. The identification of participants at nutritional risk was accomplished by combining information from interviews, questionnaires, clinical and laboratory data. Although the nutrition intervention was mainly carried out using individual nutritional counselling, other assisting methods were used as appropriate. CONCLUSION: The SPRINTT nutrition intervention was feasible and able to adapt flexibly to varying needs of this heterogeneous population. The procedures adopted to identify older adults at risk of malnutrition and to design the appropriate intervention may serve as a model to deliver nutrition intervention for community-dwelling older people with mobility limitations.

Lifestyle and 25-hydroxy-vitamin D among community-dwelling old adults with dementia, mild cognitive impairment, or normal cognitive function.

BACKGROUND: Several studies have indicated that older adults with cognitive impairment have a poorer lifestyle than their healthy peers including lower 25-hydroxy-vitamin D levels (25OHD). AIM: To investigate the associations between lifestyle and 25OHD depending on cognitive status among old adults. METHODS: Community-dwelling old adults (65-96 years) participated in this cross-sectional study based on the Age-Gene/Environment-Susceptibility-Reykjavik-Study. The analytical sample included 5162 subjects who were stratified by cognitive status, i.e., dementia (n = 307), mild cognitive impairment (MCI, n = 492), and normal cognitive status (NCS, n = 4363). Lifestyle variables were assessed and 25OHD was measured. The associations between lifestyle and 25OHD were calculated using linear models correcting for potential confounders. RESULTS: According to linear regression models, 25OHD was significantly lower in older people with dementia (53.8 ± 19.6 nmol/L) than in NCS participants (57.6 ± 17.7 nmol/L). Cod liver oil (7.1-9.2 nmol/L, P < 0.001) and dietary supplements (4.4-11.5 nmol/L, P < 0.001) were associated with higher 25OHD in all three groups. However, physical activity ≥ 3 h/week (2.82 nmol/L, P < 0.001), BMI < 30 kg/m2 (5.2 nmol/L, P < 0.001), non-smoking (4.8 nmol/L, P < 0.001), alcohol consumption (2.7 nmol/L, P < 0.001), and fatty fish consumption ≥ 3x/week (2.6 nmol/L, P < 0.001) were related to higher 25OHD in NCS only, but not in participants with dementia or MCI. DISCUSSION: Older people living in Iceland with dementia are at higher risk for 25OHD deficiency when compared to healthy individuals. Physical activity reported among participants with dementia, and MCI is low and is not significantly associated with 25OHD. CONCLUSIONS: Lifestyle factors among NCS participants are associated with 25OHD levels. Importantly, healthy lifestyle should be promoted among individuals with MCI and dementia.

The effect of cognitive function on mobility improvement among community-living older adults: A 12-week resistance exercise intervention study.

The purpose of the study was to investigate the association between baseline cognitive function and improvement in mobility after 12 weeks of resistance training (3 times/week; 3 sets, 6-8 repetitions at 75-80% of the 1-repetition maximum) among community-dwelling older adults in Iceland (N=205, 73.5±5.7 years, 57.0% female). Body composition, physical activity status, cardiovascular risk factors, 6-minute walk test (6MWT), and Mini-Mental State Examination (MMSE) were measured. The linear regression model was used to examine the association between baseline MMSE and mobility improvement. Mean distance of 6MWT was 462.8±71.6 meter at baseline and mean change after the exercise intervention was 33.7±34.9 meter. The mean MMSE score at baseline was 27.6±1.9. After adjusting for baseline covariates, we found that baseline MMSE score was significantly associated with improvement in mobility among older adults after the exercise intervention. Cognitive function strongly influences the effect of exercise intervention on mobility among older adults.

Obesity, Physical Function, and Training Success in Community-Dwelling Nonsarcopenic Old Adults.

OBJECTIVES: Obesity-related physiological changes can limit improvements of obese subjects after training. The aim was to investigate obesity, muscular strength, and physical function in community-dwelling nonsarcopenic old adults. METHODS: Nonsarcopenic subjects (N=229, 73.7 ± 5.7 years; 21% normal weight, 42% overweight, and 37% obese based on body mass index (BMI)) participated in a 12-week resistance exercise program. Leisure time physical activity (LTPA), body composition (dual-energy X-ray absorptiometry), quadriceps strength (maximum voluntary isometric contraction; absolute and relative to body weight), and physical function in terms of 6-minutes-walk-for-distance (6MWD) and timed up and go (TUG) were measured baseline and endpoint. RESULTS: At baseline, normal weight participants had lower absolute quadriceps strength (-43 ± 22 N, P=0.015) than obese, but better quadriceps strength relative to body weight (1.4 ± 0.7 N/kg, P < 0.001), 6MWD (53 ± 27 m, P < 0.001), and TUG (-1.4 ± 0.7 sec, P ≤ 0.001). LTPA was positively associated with 6MWD and TUG (both P < 0.05), but based on general linear models, differences in LTPA between BMI categories did not explain differences in 6MWD and TUG between BMI categories. During the program, dropout (11.9%) and attendance (85%) were similar between BMI groups. After the intervention, body composition and physical function significantly improved in all three BMI categories; however, normal weight participants lost more body fat (-1.53 ± 0.78%, P=0.014), gained more lean mass (0.70 ± 0.36 kg, P < 0.001) and relative quadriceps strength (0.31 ± 0.16 N/kg, P=0.017), and improved more on the 6MWD (24 ± 12 m, P < 0.001) but gained less grip strength (-2.4 ± 1.3 N/kg, P=0.020) compared to obese. There were no differences in TUG or absolute quadriceps strength changes between the BMI strata. Physical function at baseline as well as training success of overweight participants was located between the normal weight and obesity groups. CONCLUSION: Nonsarcopenic obese community-dwelling old adults have lower physical function than their normal weight counterparts. This difference is not explained by lower LTPA. A 12-week resistance exercise program improves body composition and physical function in normal weight, overweight, and obese old adults; however, obese participants experience less favorable changes in body composition and physical function than normal weight individuals. This trial is registered with NCT01074879.

Correction: The atypical ubiquitin ligase RNF31 stabilizes estrogen receptor α and modulates estrogen-stimulated breast cancer cell proliferation.

Since the publication of the above article, the authors have noted that the input data in Fig. 6E is incorrect. The correct data are included in the below Fig. 6E. The mistake does not affect the conclusions of the paper as the levels of input proteins remain similar between samples. We apologise for any inconvenience caused by this error.

Gender, Success, and Drop-Out during a Resistance Exercise Program in Community Dwelling Old Adults.

BACKGROUND: Resistance exercise training can be effective against sarcopenia. We identified predictors of drop-out and compared physical outcomes between men and women after such training. METHODS: Subjects (N = 236, 73.7 ± 5.7 years) participated in a 12-week resistance exercise program. Outcome variables were measured at baseline and endpoint. RESULTS: Drop-out was 11.9% and not significantly different between genders. Drop-outs were significantly older and had poorer strength and physical function in comparison to completers. Anthropometrics, QoL, and cognitive function were not related to drop-out. According to multivariate analysis, gait speed and physical activity were the strongest predictors of drop-out. After the training, gains in lean mass or appendicular muscle were significantly higher in men than women; however relative gains in appendicular muscle as well as absolute improvements in strength and function were similar in men and women, respectively. CONCLUSIONS: Participants who drop out are older, have poorer physical function, and are less physically active. Old women do not drop out more frequently than men and show meaningful improvements in relevant outcomes similar to men after such a training program. The trial is registered at the US National Library of Medicine (NCT01074879).

Neutral processes forming large clones during colonization of new areas.

In species reproducing both sexually and asexually clones are often more common in recently established populations. Earlier studies have suggested that this pattern arises due to natural selection favouring generally or locally successful genotypes in new environments. Alternatively, as we show here, this pattern may result from neutral processes during species' range expansions. We model a dioecious species expanding into a new area in which all individuals are capable of both sexual and asexual reproduction, and all individuals have equal survival rates and dispersal distances. Even under conditions that favour sexual recruitment in the long run, colonization starts with an asexual wave. After colonization is completed, a sexual wave erodes clonal dominance. If individuals reproduce more than one season, and with only local dispersal, a few large clones typically dominate for thousands of reproductive seasons. Adding occasional long-distance dispersal, more dominant clones emerge, but they persist for a shorter period of time. The general mechanism involved is simple: edge effects at the expansion front favour asexual (uniparental) recruitment where potential mates are rare. Specifically, our model shows that neutral processes (with respect to genotype fitness) during the population expansion, such as random dispersal and demographic stochasticity, produce genotype patterns that differ from the patterns arising in a selection model. The comparison with empirical data from a post-glacially established seaweed species (Fucus radicans) shows that in this case, a neutral mechanism is strongly supported.

During warfarin induction, the Fiix-prothrombin time reflects the anticoagulation level better than the standard prothrombin time.

Essentials Fiix-prothrombin time (PT) monitoring of warfarin measuring factor (F) II and X, is effective. Plasma obtained during warfarin induction and stable phase in Fiix-trial was assayed. Fiix-PT stabilized anticoagulation earlier than monitoring with traditional PT-INR. FVII had little effect on thrombin generation that was mainly determined by FII and FX. SUMMARY: Background The prothrombin time (PT) is equally prolonged by reduction of each of the vitamin K-dependent (VKD) factors (F) II, VII and X. The Fiix-PT is only affected by FII and FX, the main contributors to thrombin generation (TG). Objective To test the hypothesis that variability in warfarin anticoagulation is reduced early during monitoring with the normalized PT-ratio calculated from Fiix-PT (Fiix-International Normalized Ratio [INR]) compared with traditional PT-INR monitoring. Also, that because of its insensitivity to FVII, Fiix-PT more accurately reflects TG when Fiix-INR and PT-INR are discrepant. Methods Samples from Fiix-trial participants monitored with either Fiix-PT or PT were used. VKD coagulation factors and TG were measured in samples from 40 patients during stable anticoagulation and in serial samples obtained from 26 patients during warfarin induction. TG was assessed in relation to selective reduction in single VKD factors. Results During Fiix-warfarin induction full anticoagulation measured as FII or FX activity was achieved at a similar rate to that with PT-warfarin but subsequently stabilized better. Fiix-INR but not PT-INR mirrored total TG during initiation. During induction, FII (R2 = 0.66) and FX (R2 = 0.52) correlated better with TG and with a steeper slope than did FIX (R2 = 0.37) and in particular FVII (R2 = 0.21). In vitro, FII and FX were the main determinants of TG at concentrations observed during VKA anticoagulation, whereas FVII and FIX had little influence. Conclusions Fiix-PT monitoring reduces anticoagulation variability, suggesting that monitoring FVII has a limited role during VKA management. TG is better reflected by Fiix-PT.

Health Technology Assessment in the Context of Adaptive Pathways for Medicines in Europe: Challenges and Opportunities.

Adaptive pathways for medicines have gained momentum and, in Europe, adaptive pathways have recently been introduced into the European Medicines Agency (EMA) processes after a successful 2-year pilot. Although the concept, as initially proposed, contained several elements that would have required regulatory reforms, the adaptive pathways program has developed a more pragmatic scope (Box 1). In this article, we explore the main challenges and opportunities adaptive pathways pose from a European health technology assessment (HTA) perspective.

Preferential Sampling and Small-Scale Clustering of Gyrotactic Microswimmers in Turbulence.

Recent studies show that spherical motile microorganisms in turbulence subject to gravitational torques gather in down-welling regions of the turbulent flow. By analyzing a statistical model we analytically compute how shape affects the dynamics, preferential sampling, and small-scale spatial clustering. We find that oblong organisms may spend more time in up-welling regions of the flow, and that all organisms are biased to regions of positive fluid-velocity gradients in the upward direction. We analyze small-scale spatial clustering and find that oblong particles may either cluster more or less than spherical ones, depending on the strength of the gravitational torques.