Effect of physical exercise on cognitive function after chemotherapy in patients with breast cancer: a randomized controlled trial (PAM study).

BACKGROUND: Up to 60% of breast cancer patients treated with chemotherapy is confronted with cognitive problems, which can have a significant impact on daily activities and quality of life (QoL). We investigated whether exercise training improves cognition in chemotherapy-exposed breast cancer patients 2-4 years after diagnosis. METHODS: Chemotherapy-exposed breast cancer patients, with both self-reported cognitive problems and lower than expected performance on neuropsychological tests, were randomized to an exercise or control group. The 6-month exercise intervention consisted of supervised aerobic and strength training (2 h/week), and Nordic/power walking (2 h/week). Our primary outcome was memory functioning (Hopkins Verbal Learning Test-Revised; HVLT-R). Secondary outcomes included online neuropsychological tests (Amsterdam Cognition Scan; ACS), self-reported cognition (MD Anderson Symptom Inventory for multiple myeloma; MDASI-MM), physical fitness (relative maximum oxygen uptake; VO2peak), fatigue (Multidimensional Fatigue Inventory), QoL (European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire; EORTC QLQ C-30), depression (Patient Health Questionnaire-9, Hospital Anxiety and Depression Scale; HADS), and anxiety (HADS). HVLT-R total recall was analyzed with a Fisher exact test for clinically relevant improvement (≥ 5 words). Other outcomes were analyzed using multiple regression analyses adjusted for baseline and stratification factors. RESULTS: We randomized 181 patients to the exercise (n = 91) or control group (n = 90). Two-third of the patients attended ≥ 80% of the exercise sessions, and physical fitness significantly improved compared to control patients (B VO2peak 1.4 ml/min/kg, 95%CI:0.6;2.2). No difference in favor of the intervention group was seen on the primary outcome. Significant beneficial intervention effects were found for self-reported cognitive functioning [MDASI-MM severity (B-0.7, 95% CI - 1.2; - 0.1)], fatigue, QoL, and depression. A hypothesis-driven analysis in highly fatigued patients showed positive exercise effects on tested cognitive functioning [ACS Reaction Time (B-26.8, 95% CI - 52.9; - 0.6) and ACS Wordlist Learning (B4.4, 95% CI 0.5; 8.3)]. CONCLUSIONS: A 6-month exercise intervention improved self-reported cognitive functioning, physical fitness, fatigue, QoL, and depression in chemotherapy-exposed breast cancer patients with cognitive problems. Tested cognitive functioning was not affected. However, subgroup analysis indicated a positive effect of exercise on tested cognitive functioning in highly fatigued patients. Trial Registration Netherlands Trial Registry: Trial NL5924 (NTR6104). Registered 24 October 2016, https://www.trialregister.nl/trial/5924 .

Feasibility and outcomes of a goal-directed physical therapy program for patients with metastatic breast cancer.

PURPOSE: To evaluate the feasibility and outcomes of a tailored, goal-directed, and exercise-based physical therapy program for patients with metastatic breast cancer (MBC). METHODS: This was an observational, uncontrolled feasibility study. The physical therapy intervention was highly tailored to the individual patient's goals, abilities, and preferences and could include functional, strength, aerobic, and relaxation exercises. Feasibility outcomes were participation rate (expected: 25%), safety, and adherence (percentage of attended sessions relative to scheduled sessions). Additional outcomes were goal attainment, self-reported physical functioning, fatigue, health-related quality of life, and patient and physical therapist satisfaction with the program. RESULTS: Fifty-five patients (estimated participation rate: 34%) were enrolled. Three patients did not start the intervention due to early disease progression. An additional 22 patients discontinued the program prematurely, mainly due to disease progression. Median intervention adherence was 90% and no major intervention-related adverse events occurred. A goal attainment score was available for 42 patients (of whom 29 had completed the program and 13 had prematurely dropped out). Twenty-two (52%) of these patients achieved their main goal fully or largely and an additional 15 patients (36%) partially. Eighty-five percent would "definitely recommend" the program to other patients with MBC. We observed a modest improvement in patient satisfaction with physical activities (Cohen's dz 0.33). CONCLUSION: The tailored intervention program was feasible in terms of uptake, safety, and outcomes and was highly valued by patients and physical therapists. However, disease progression interfered with the program, leading to substantial dropout. TRIAL REGISTRATION: NTR register: NTR6475.

The Timed Swallowing Proficiency for Eating and Drinking (SPEAD) Test: Development and Initial Validation of an Instrument to Objectify (Impaired) Swallowing Capacity in Head and Neck Cancer Patients.

Objective swallowing outcomes measure the physical swallowing function, while subjective outcomes measure swallowing perception. A test for swallowing capacity, measuring the ingestion of all consistencies is currently not available. Therefore, the Swallowing Proficiency for Eating And Drinking (SPEAD) test was developed. It entails the timed ingestion of thin liquid, thick liquid and solid. In this study, its feasibility, reliability and validity were evaluated in patients with dysphagia after treatment for head and neck cancer (HNC) and healthy participants. Thirty-eight HNC patients and forty healthy participants were enrolled in this study and performed the SPEAD test three times. Video recordings of the test were evaluated three times by one observer, and once by three additional observers, to assess test-retest, intra-rater and inter-rater reliability. Validity was assessed by calculating effect sizes for the difference between results of patients and healthy participants and by evaluating correlations with objective (e.g., videofluoroscopy and functional oral intake scale) and subjective (e.g., SWAL-QOL) swallowing outcomes. Test-retest, intra-rater and inter-rater reliability of ingestion duration was good to excellent. All hypotheses with regard to magnitude and direction of correlations were confirmed, supporting construct validity of the test. Our initial results suggest that the SPEAD test reliably measures the transport capacity of the upper digestive tract (in grams per second) and that this test can be useful to objectively evaluate and monitor the (safe) swallowing capacity in HNC patients, in both research as well as daily clinical practice.

The association between preoperative fatigue and instrumental activities in daily living with complications and length of hospital stay in patients undergoing colorectal surgery.

BACKGROUND: The incidence of colorectal cancer (CRC) is highest among the elderly. An important treatment modality is surgery. After surgery, due to poor functional recovery, some elderly have an increased risk for complications and prolonged length of hospital stay (LOS). Preoperative elevated levels of fatigue and impaired functioning in instrumental activities of daily living (iADL) might be associated with these outcomes, and may, therefore, be helpful to recognize patients with elevated risk for complications or prolonged LOS, who should undergo more thorough functional assessment. AIMS: This exploratory study aims to assess whether physical fatigue, reduced activity and/or iADL, assessed preoperatively, are associated with postoperative complications and prolonged LOS, in elderly patients undergoing surgery for CRC. METHODS: We performed an exploratory prospective study in older (≥ 65 years) patients (n = 57) who were scheduled to undergo elective surgery for colorectal cancer. Fatigue and iADL functioning were assessed with questionnaires. Multivariable regression analyses were used to examine the relationship of fatigue and iADL with complications and LOS. RESULTS: IADL was not associated with complications or LOS. Fatigue was not associated with complications. Patients with higher fatigue had increased LOS in the univariable analyses but not in the multivariable analyses after adjustment for nutritional status and neoadjuvant treatment. DISCUSSION: We found that fatigue was associated with increased LOS in the univariable analysis. The results from the multivariable analysis and path analysis indicate, however, that this is likely not a causal relationship; the observed relationship between physical fatigue and LOS appears to be confounded by nutritional status and by having received neoadjuvant treatment. CONCLUSIONS: Although fatigue is a predictor for increased LOS, assessment of fatigue and iADL has no additional value for identifying elderly at risk for poor functional outcome after CRC surgery.

Which cancer survivors are at risk for a physically inactive and sedentary lifestyle? Results from pooled accelerometer data of 1447 cancer survivors.

BACKGROUND: Physical activity has beneficial effects on the health of cancer survivors. We aimed to investigate accelerometer-assessed physical activity and sedentary time in cancer survivors, and describe activity profiles. Additionally, we identify demographic and clinical correlates of physical activity, sedentary time and activity profiles. METHODS: Accelerometer, questionnaire and clinical data from eight studies conducted in four countries (n = 1447) were pooled. We calculated sedentary time and time spent in physical activity at various intensities using Freedson cut-points. We used latent profile analysis to identify activity profiles, and multilevel linear regression analyses to identify demographic and clinical variables associated with accelerometer-assessed moderate to vigorous physical activity (MVPA), sedentary time, the highly active and highly sedentary profile, adjusting for confounders identified using a directed acyclic graph. RESULTS: Participants spent on average 26 min (3%) in MVPA and 568 min (66%) sedentary per day. We identified six activity profiles. Older participants, smokers and participants with obesity had significantly lower MVPA and higher sedentary time. Furthermore, men had significantly higher MVPA and sedentary time than women and participants who reported less fatigue had higher MVPA time. The highly active profile included survivors with high education level and normal body mass index. Haematological cancer survivors were less likely to have a highly active profile compared to breast cancer survivors. The highly sedentary profile included older participants, males, participants who were not married, obese, smokers, and those < 12 months after diagnosis. CONCLUSIONS: Cancer survivors engage in few minutes of MVPA and spend a large proportion of their day sedentary. Correlates of MVPA, sedentary time and activity profiles can be used to identify cancer survivors at risk for a sedentary and inactive lifestyle.

(Cost-)effectiveness of an internet-based physical activity support program (with and without physiotherapy counselling) on physical activity levels of breast and prostate cancer survivors: design of the PABLO trial.

BACKGROUND: Higher levels of physical activity (PA) after treatment are associated with beneficial effects on physical and psychosocial functioning of cancer survivors. However, survivors often do not meet the recommended levels of PA. In order to promote PA, we developed a closed internet-based program. The aim of the study is to evaluate the (cost-)effectiveness of an internet-based PA-promotion program, alone or combined with physiotherapy counselling, compared to usual care, on PA-levels of breast or prostate cancer survivors. In this multicenter randomised controlled trial (RCT), breast or prostate cancer survivors who completed their primary treatment 3-12 months earlier, will be randomised to either 6-months access to a fully-automated internet-based intervention alone, an internet-based intervention plus remote support by a physiotherapist, or a control group. The intervention is based on the Transtheoretical Model and includes personalized feedback, information, video's and assignments. Additionally, in a second arm, physiotherapy counselling is provided through monthly scheduled and on-demand telephone calls. The control group will receive usual care and a leaflet with PA guidelines. METHODS: At baseline, 6 and 12 months, the primary outcome (PA) will be measured during 7 consecutive days by accelerometers. Secondary outcomes are self-reported PA, fatigue, mood, health-related quality of life, and costs. The group differences for primary and secondary outcomes will be analyzed using linear mixed models. DISCUSSION: If proven to be (cost)effective, this internet-based intervention, either alone or in combination with telephone support, will be a welcome addition to previous RCT's. TRIAL REGISTRATION: Netherlands trial register (NTR6911), Date of trial registration: December 21, 2017.

Comparison of symptom clusters associated with fatigue in older and younger survivors of colorectal cancer.

PURPOSE: Cancer-related fatigue (CRF) is one of the most frequently reported symptoms in cancer survivors. To be able to optimally treat CRF, knowledge of symptoms that interact with CRF is helpful. During aging, changes occur in body composition with progressive deterioration in physiological functions and metabolic processes causing a decline of adaptive capacity. Therefore, symptoms caused by cancer and its treatment might coexist in different symptom clusters in older cancer survivors, compared to younger survivors. The purpose of this analysis was to identify and compare symptom clusters that include CRF between older and younger survivors of colorectal cancer (CRC). METHODS: Data were drawn from a cross-sectional study from the Netherlands Cancer Registry. In total, 1698 stage I and II CRC survivors diagnosed from 2000 to 2009 completed questionnaires on fatigue and psychological distress. Survivors were categorized in two groups based on age (≤65 versus >65 years) Symptom clusters were assessed using principal component analysis. A sensitivity analysis was performed on the results with categorical principal component analysis. RESULTS: In both age groups, three components including two symptom clusters were identified: an emotional symptom cluster containing anxiety, fatigue, and depression; a pain symptom cluster containing pain and insomnia; and a third component containing dyspnea only. CONCLUSIONS: Symptom clusters in survivors of CRC appear to be independent of age. In treating CRC survivors for fatigue, regardless of age, it is advisable to assess depression and anxiety and, if necessary, refer for further diagnosis and treatment.

Effects of Strengthening Exercises on Swallowing Musculature and Function in Senior Healthy Subjects: a Prospective Effectiveness and Feasibility Study.

Head and neck cancer (HNC) patients may develop dysphagia due to muscle atrophy and fibrosis following chemoradiotherapy. Strengthening of the swallowing muscles through therapeutic exercise is potentially effective for improving swallowing function. We hypothesize that a customized Swallow Exercise Aid (SEA), developed for isometric and isokinetic strengthening exercises (against resistance), can help to functionally strengthen the suprahyoid musculature, which in turn can improve swallowing function. An effectiveness/feasibility study was carried out with ten senior healthy volunteers, who performed exercises 3 times per day for 6 weeks. Exercises included chin tuck against resistance (CTAR), jaw opening against resistance (JOAR), and effortful swallow exercises with the SEA. Multidimensional assessment consisted of measurements of maximum chin tuck and jaw opening strength, maximum tongue strength/endurance, suprahyoid muscle volume, hyoid bone displacement, swallowing transport times, occurrence of laryngeal penetration/aspiration and/or contrast residue, maximum mouth opening, feasibility/compliance (questionnaires), and subjective swallowing complaints (SWAL-QOL). After 6-weeks exercise, mean chin tuck strength, jaw opening strength, anterior tongue strength, suprahyoid muscle volume, and maximum mouth opening significantly increased (p < .05). Feasibility and compliance (median 86 %, range 48-100 %) of the SEA exercises were good. This prospective effectiveness/feasibility study on the effects of CTAR/JOAR isometric and isokinetic strengthening exercises on swallowing musculature and function shows that senior healthy subjects are able to significantly increase swallowing muscle strength and volume after a 6-week training period. These positive results warrant further investigation of effectiveness and feasibility of these SEA exercises in HNC patients with dysphagia.

No evidence of benefit from class-II compression stockings in the prevention of lower-limb lymphedema after inguinal lymph node dissection: results of a randomized controlled trial.

Graduated compression stockings have been advocated for prevention of lymphedema after inguinal lymph node dissection (ILND) although scientific evidence of their efficacy in preventing lymphedema is lacking. The primary objective of this study was to assess the efficacy of class II compression stockings for the prevention of lymphedema in cancer patients following ILND. Secondary objectives were to investigate the influence of stockings on the occurrence of wound complications and genital edema, health-related quality of life (HRQoL) and body image. Eighty patients (45 with melanoma, 35 with urogenital tumors) who underwent ILND at two specialized cancer centers were randomly allocated to class II compression stocking use for six months or to a usual care control group. Lymphedema of the leg and genital area, wound complications, HRQoL, and body image were assessed at regular intervals prior to and up to 12 months after ILND. No significant differences were observed between groups in the incidence of edema, median time to the occurrence of edema, incidence of genital edema, frequency of complications, HRQoL, or body image. Based on the results of the current study, routine prescription of class II graduated compression stockings after ILND should be questioned and alternative prevention strategies should be considered.

Evaluating the psychometric properties of the Grit scale in Marine recruits using Rasch analysis.

INTRODUCTION: Successful completion of initial military training has been suggested to be predicted by physical abilities, cognitive abilities and non-cognitive abilities such as hardiness and grit. This study aimed to assess the psychometric properties of a Dutch version of a grit measurement scale: the NL-Grit scale. METHODS: We assessed the factor structure, unidimensionality of the subscales, discriminative quality of the rating scale and investigated to what extend the items together can reliably measure the entire range of grit levels in Dutch Marine recruits. We used data of Marine recruit training platoons of the Royal Netherlands Marine Corps. RESULTS: Principal component analysis reflected two subscales: 'consistency of interests' and 'perseverance of effort'. Rasch analysis confirmed the unidimensionality of the intended subscales. Rasch rating scale analysis indicated that the five-point response scale was not used as intended by respondents. Disordered rating scale categories were collapsed to obtain ordered rating categories. The item and person parameters (grit levels) largely overlapped, indicating that the item spread was sufficient for measuring the entire range of grit trait levels. However, larger gaps between item location parameters suggested a low discriminative capacity of the NL-Grit scale for respondents with trait levels within the gaps. CONCLUSION: Our evaluation of the NL-Grit scale suggests sound psychometric quality of the NL-Grit in Dutch Marine recruits. Reliability could be improved by adding items to fill the observed gaps in item content.

Worsening tricuspid regurgitation after ICD implantation is rather due to transvenous lead than natural progression.

BACKGROUND: Transvenous implantable cardioverter-defibrillators (TV-ICDs) are associated with greater tricuspid regurgitation (TR) severity, which leads to increased mortality. The pathophysiology is assumed to be lead-related, hence, treatment includes lead extraction. However, TR may also naturally occur in the high-risk ICD population, or may be caused by right ventricular pacing. We sought to evaluate the effect of ICD type (with or without lead) and pacing percentage on post-implantation TR severity. METHODS: In this retrospective cohort study, consecutive patients were included with a primary S-ICD or TV-ICD implantation between 2009 and 2019 and echocardiography studies ≤3 months before and ≤ 3 years post-implantation. The effect of ICD type on TR severity at follow-up was estimated adjusting for ventricular pacing percentage and potential confounders. The effect of ventricular pacing percentage on TR severity at follow-up was adjusted for potential confounders. RESULTS: 118 patients were included (mean age 52 ± 21): 31 (26%) with an S-ICD and 87 (74%) with a TV-ICD. Median 20 months post-implantation, worsening TR was found in 11/31 (34%) S-ICD patients and 45/87 (52%) TV-ICD patients (p = 0.15). Adjusted for age, atrial fibrillation, baseline TR and mitral regurgitation, ventricular pacing percentage, ICD dwelling time, BMI, hypertension and left ventricular ejection fraction, TV-ICDs were significantly associated with greater TR severity (OR 9.90, p = 0.002). Ventricular pacing percentage was very low, and not significantly associated with greater TR severity (OR 0.95, p = 0.066). CONCLUSIONS: Our results suggest that greater TR severity in ICD patients is mainly caused by the transvenous lead, rather than natural progression in the ICD population.

Effect of physical exercise on the hippocampus and global grey matter volume in breast cancer patients: A randomized controlled trial (PAM study).

BACKGROUND: Physical exercise in cancer patients is a promising intervention to improve cognition and increase brain volume, including hippocampal volume. We investigated whether a 6-month exercise intervention primarily impacts total hippocampal volume and additionally hippocampal subfield volumes, cortical thickness and grey matter volume in previously physically inactive breast cancer patients. Furthermore, we evaluated associations with verbal memory. METHODS: Chemotherapy-exposed breast cancer patients (stage I-III, 2-4 years post diagnosis) with cognitive problems were included and randomized in an exercise intervention (n = 70, age = 52.5 ± 9.0 years) or control group (n = 72, age = 53.2 ± 8.6 years). The intervention consisted of 2x1 hours/week of supervised aerobic and strength training and 2x1 hours/week Nordic or power walking. At baseline and at 6-month follow-up, volumetric brain measures were derived from 3D T1-weighted 3T magnetic resonance imaging scans, including hippocampal (subfield) volume (FreeSurfer), cortical thickness (CAT12), and grey matter volume (voxel-based morphometry CAT12). Physical fitness was measured with a cardiopulmonary exercise test. Memory functioning was measured with the Hopkins Verbal Learning Test-Revised (HVLT-R total recall) and Wordlist Learning of an online cognitive test battery, the Amsterdam Cognition Scan (ACS Wordlist Learning). An explorative analysis was conducted in highly fatigued patients (score of ≥ 39 on the symptom scale 'fatigue' of the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire), as previous research in this dataset has shown that the intervention improved cognition only in these patients. RESULTS: Multiple regression analyses and voxel-based morphometry revealed no significant intervention effects on brain volume, although at baseline increased physical fitness was significantly related to larger brain volume (e.g., total hippocampal volume: R = 0.32, B = 21.7 mm3, 95 % CI = 3.0 - 40.4). Subgroup analyses showed an intervention effect in highly fatigued patients. Unexpectedly, these patients had significant reductions in hippocampal volume, compared to the control group (e.g., total hippocampal volume: B = -52.3 mm3, 95 % CI = -100.3 - -4.4)), which was related to improved memory functioning (HVLT-R total recall: B = -0.022, 95 % CI = -0.039 - -0.005; ACS Wordlist Learning: B = -0.039, 95 % CI = -0.062 - -0.015). CONCLUSIONS: No exercise intervention effects were found on hippocampal volume, hippocampal subfield volumes, cortical thickness or grey matter volume for the entire intervention group. Contrary to what we expected, in highly fatigued patients a reduction in hippocampal volume was found after the intervention, which was related to improved memory functioning. These results suggest that physical fitness may benefit cognition in specific groups and stress the importance of further research into the biological basis of this finding.

One out of four recruits drops out from elite military training due to musculoskeletal injuries in the Netherlands Armed Forces.

INTRODUCTION: Musculoskeletal injuries (MSIs) are among the main causes of dropout from military training. The main purpose of this study was to provide an overview of dropout rates and MSI incidence rates during elite military training. Second, this study aimed to explore restricted training days due to MSIs and to describe MSI-care by military physicians. METHODS: In a retrospective observational study, we collected dropout rates and injury surveillance data from the electronic patient records of two elite units of the Netherlands Armed Forces (NAF): the Royal Netherlands Marine Corps (RNLMC) and the Airmobile Brigade (AMB), from 1 January 2015 until 31 December 2017. RESULTS: In the RNLMC, total dropout rate was 53.9% and dropout due to MSIs was 23%. The most frequently affected locations were foot, knee and leg. In the AMB total dropout rate was 52.6% and dropout due to MSIs was 25%. In the AMB, the most frequently affected locations were back, knee and leg. Average restricted training days due to MSIs ranged between 8.3 and 20.8 days/injury. MSI-care by military physicians consisted mostly of the provision of injury-specific information and (self-)management options, imposing a specific activity restriction and referral to physiotherapy. CONCLUSION: Our study findings showed that one out of four recruits who dropout from elite military training in the NAF, do so due to MSIs. Redesigning training programmes with the objective to reduce MSIs should be given high priority, as this may reduce dropout substantially.

Effects of and Lessons Learned from an Internet-Based Physical Activity Support Program (with and without Physiotherapist Telephone Counselling) on Physical Activity Levels of Breast and Prostate Cancer Survivors: The PABLO Randomized Controlled Trial.

BACKGROUND: We developed an Internet-based physical activity (PA) support program (IPAS), which is embedded in a patient portal. We evaluated the effectiveness and costs of IPAS alone (online only) or IPAS combined with physiotherapist telephone counselling (blended care), compared to a control group. METHODS: Breast or prostate cancer survivors, 3-36 months after completing primary treatment, were randomized to 6-months access to online only, blended care, or a control group. At baseline and 6-month post-baseline, minutes of moderate-to-vigorous PA (MVPA) were measured by accelerometers. Secondary outcomes were self-reported PA, fatigue, mood, health-related quality of life, attitude toward PA, and costs. (Generalized) linear models were used to compare the outcomes between groups. RESULTS: We recruited 137 survivors (participation rate 11%). We did not observe any significant between-group differences in MVPA or secondary outcomes. Adherence was rather low and satisfaction scores were low to moderate, with better scores for blended care. Costs for both interventions were low. CONCLUSIONS: Recruitment to the study was challenging and the interventions were less efficacious than anticipated, which led to lessons learned for future trials. Suggestions for future research are as follows: improved accessibility of the support program, increased frequency of support, and use of activity trackers.

The autoantigen Ku is indistinguishable from NF IV, a protein forming multimeric protein-DNA complexes.

We have isolated a cDNA encoding the 84-kD subunit of NFIV. Tryptic peptide sequences were identified within the coding sequences, confirming its proper identity. The primary sequence of the protein is identical to that of the large subunit of the Ku autoantigen. A missing NFIV peptide sequence was identified within the sequence of the small subunit of Ku. In addition, the proteins are identical in immunological aspects. We suggest that the Ku and NFIV proteins are identical. This connection adds new biochemical data to our knowledge of the Ku autoantigen.

Despite an improved aerobic endurance, still high attrition rates in initially low-fit recruits-results of a randomised controlled trial.

BACKGROUND: Low baseline fitness of recruits entering basic military training (BMT) is associated with an increased risk of musculoskeletal injuries (MSIs) and attrition from training. OBJECTIVE: To determine the effects of a pre-training conditioning program (PCP) on aerobic endurance, incidence of musculoskeletal injuries (MSIs), and attrition rates in BMT of a special infantry unit of the Netherlands Armed Forces. PARTICIPANTS: Recruits were considered eligible for this study when they were 'low-fit' at the start of BMT (time to complete a 2.7-km run ≥ 12'23″). INTERVENTIONS: 'Low-fit' recruits were deferred to a seven to twelve week-depending on the time between two consecutive training platoons-PCP consisting of functional training to improve several fitness domains. The control (CON) group started regular BMT without delay. RESULTS: Forty-nine recruits were included in this study; 26 in the PCP-group and 23 in the CON-group. Recruits who followed the PCP started BMT with better aerobic endurance than the CON-group who started BMT immediately (2.7 km run timings: PCP 11'32″, CON 13'16″). The risk of dropout was lower in the PCP-group (incidence density ratio (IDR) 0.63, 95%CI 0.32; 1.26), but dropout due to training-related MSIs was more frequent (IDR 1.23, 95%CI 0.32; 4.76 (per-protocol 0.94, 95%CI 0.24; 3.63), without statistically significant differences between the groups. CONCLUSION: Although a PCP was effective to improve aerobic endurance in low-fit recruits to return to meet pre-enlistment fitness criteria, we could not demonstrate an effect on dropout from military training. TRIAL REGISTRATION: Dutch trial register Trial NL6791 (NTR6977) https://www.trialregister.nl/trial/6791.

Carbon-14 dating: a comparison of Beta and ion counting.

Accelerator ion counting compares favorably with conventional beta counting. The major advantage of ion counting is that milligram samples can be analyzed. When sample size is not limiting, ion counting complements beta counting for the more routine carbon-14 determinations. Further development is needed before ion counting can achieve the same high precision as beta counting for large samples (+/- 2 per mil). A solution to the background variability has to be found before ion counting can be used to date samples back to the 75,000-year limit of beta counting.

Atmospheric carbon dioxide and carbon reservoir changes.

The net release of CO(2) from the biosphere to the atmosphere between 1850 and 1950 is estimated to amount to 1.2 x 10(9) tons of carbon per year. During this interval, changes in land use reduced the total terrestrial biomass by 7 percent. There has been a smaller reduction in biomass over the last few decades. In the middle 19th century the air had a CO(2) content of approximately 268 parts per millon, and the total increase in atmospheric CO(2) content since 1850 has been 18 percent. Major sinks for fossil fuel CO(2) are the thermocline regions of large oceanic gyres. About 34 percent of the excess CO(2) generated so far is stored in surface and thermocline gyre waters, and 13 percent has been advected into the deep sea. This leaves an airborne fraction of 53 percent.

Oxygen-18 content of atmospheric precipitation during last 11,000 years in the Great Lakes region.

Freshwater lake marl and mollusks from Indiana show variations in ratios of oxygen-18 to oxygen-16 of a few per mil during the Postglacial. For the last 9000 years these variations are about 1 per mil for properly selected lake sediments. Thus the oxygen isotope composition of atmospheric precipitation appears relatively stable over this interval, indicating stationary atmospheric circulation patterns over the Great Lakes region. A reduction in oxygen-18 content around 10,000 years ago corresponds with the climate change indicated by pollen profiles. Large systematic differences were found between carbon-13 and oxygen-18 content of marl and mollusks.

Changes in atmospheric carbon-14 attributed to a variable sun.

The (14)C production rate in the upper atmosphere changes with time because the galactic cosmic-ray flux responsible for (14)C production is modulated by the changes in solar wind magnetic properties. The resulting changes in the atmospheric (14)C level are recorded in tree rings and are used to calculate past (14)C production rates from a carbon reservoir model that describes terrestrial carbon exchange between the atmosphere, ocean, and biosphere. These past (14)C production rate changes are compared with (14)C production rates determined from 20th-century neutron flux measurements, and a theory relating (14)C production and solar variability, as given by geomagnetic Aa indices and sunspot numbers, is developed. This theory takes into account long-term solar changes that were previously neglected. The 860-year (14)C record indicates three episodes when sunspots apparently were absent: A.D. 1654 to 1714 (Maunder minimum), 1416 to 1534 (Spörer minimum), and 1282 to 1342 (Wolf minimum). A less precisely defined minimum occurred near A.D. 1040. The part of this record after A.D. 1645 correlates well with the basic features of the historical record of sunspot numbers. The magnitude of the calculated (14)C production rates points to a further increase in cosmic-ray flux when sunspots are absent. This flux was greatest during the Spörer minimum. A record of approximate sunspot numbers and Aa indices for the current millennium is also presented.