Exercise is medicine in oncology: Engaging clinicians to help patients move through cancer.

Multiple organizations around the world have issued evidence-based exercise guidance for patients with cancer and cancer survivors. Recently, the American College of Sports Medicine has updated its exercise guidance for cancer prevention as well as for the prevention and treatment of a variety of cancer health-related outcomes (eg, fatigue, anxiety, depression, function, and quality of life). Despite these guidelines, the majority of people living with and beyond cancer are not regularly physically active. Among the reasons for this is a lack of clarity on the part of those who work in oncology clinical settings of their role in assessing, advising, and referring patients to exercise. The authors propose using the American College of Sports Medicine's Exercise Is Medicine initiative to address this practice gap. The simple proposal is for clinicians to assess, advise, and refer patients to either home-based or community-based exercise or for further evaluation and intervention in outpatient rehabilitation. To do this will require care coordination with appropriate professionals as well as change in the behaviors of clinicians, patients, and those who deliver the rehabilitation and exercise programming. Behavior change is one of many challenges to enacting the proposed practice changes. Other implementation challenges include capacity for triage and referral, the need for a program registry, costs and compensation, and workforce development. In conclusion, there is a call to action for key stakeholders to create the infrastructure and cultural adaptations needed so that all people living with and beyond cancer can be as active as is possible for them.

Weight management and physical activity throughout the cancer care continuum.

Mounting evidence suggests that weight management and physical activity (PA) improve overall health and well being, and reduce the risk of morbidity and mortality among cancer survivors. Although many opportunities exist to include weight management and PA in routine cancer care, several barriers remain. This review summarizes key topics addressed in a recent National Academies of Science, Engineering, and Medicine workshop entitled, "Incorporating Weight Management and Physical Activity Throughout the Cancer Care Continuum." Discussions related to body weight and PA among cancer survivors included: 1) current knowledge and gaps related to health outcomes; 2) effective intervention approaches; 3) addressing the needs of diverse populations of cancer survivors; 4) opportunities and challenges of workforce, care coordination, and technologies for program implementation; 5) models of care; and 6) program coverage. While more discoveries are still needed for the provision of optimal weight-management and PA programs for cancer survivors, obesity and inactivity currently jeopardize their overall health and quality of life. Actionable future directions are presented for research; practice and policy changes required to assure the availability of effective, affordable, and feasible weight management; and PA services for all cancer survivors as a part of their routine cancer care. CA Cancer J Clin 2018;68:64-89. © 2017 American Cancer Society.

Milk production of cows grazing pasture supplemented with grain mixes containing canola meal or corn grain or both over the first 100 days of lactation.

Grain mixes varying in proportions of wheat grain, barley grain, canola meal, and corn grain were fed to grazing dairy cows in early lactation to determine the contribution of canola meal and corn grain to milk yield, BW, BCS, eating behavior, and blood serum metabolite concentrations. The experiment used 80 multiparous, seasonally calving Holstein-Friesian dairy cows during the first 100 d of lactation, the treatment period, and over the subsequent carryover period of 100 d, during which all cows were fed a common diet. Cows were divided into 4 cohorts (blocks) based on calving date and within each cohort, 5 cows were randomly allocated to each of the 4 treatments. Dietary treatments included disc-milled grain mixes comprising (on a DM basis) (1) a control treatment of wheat (25%) and barley (75%); (2) wheat (25%), barley (50%), and canola meal (25%); (3) wheat (25%), barley (50%), and corn (25%), and (4) wheat (25%), barley (25%), canola meal (25%), and corn (25%). Treatment diets were introduced at 19 DIM ± 4.7 d, which included a 7-d adaptation period and were applied up until 100 DIM. Each grain mix was fed at 9 kg of DM/cow per day, offered twice daily, in equal proportions in the parlor at milking times. In addition to the grain mix, all cows grazed perennial ryegrass pasture at a daily allowance of ∼35 kg of DM/cow per day (measured to ground level). Results were analyzed in terms of corn and canola presence or absence in the diet. Including canola meal in grain mixes increased grain intake and pasture intake by 0.6 and 2.1 kg of DM/cow per day, respectively, resulting in an increased milk yield of 2.6 kg/cow per day during the first 100 d of lactation. Including canola meal also increased yields of milk fat and protein, and concentrations of milk fat, as well as increasing mean BW and BCS over the 100 d. The inclusion of canola meal in the grain mixes also resulted in greater blood serum BHB and urea concentrations, compared with feeding grain mixes that did not contain canola meal. The inclusion of corn grain provided no milk production benefits and did not change BW, BCS, or any feeding behavior variables. There were no carryover effects on milk production from either canola meal or corn grain after the treatment period. In summary, the results demonstrate that the provision of canola meal in grain mixes can improve milk production and increase mean BCS. Further, there are no benefits to milk yield when a proportion of barley is substituted for corn, in a wheat and barley grain mix fed to grazing dairy cows in early lactation. However, these results are dependent on the level of inclusion and the feeding system employed.

Isolated lesions of the pubis.

The osseous pelvis is a well-known area of various primary and secondary bone tumours, tumour mimics, and infections. Isolated lesions of the pubis (ILP) are rare, with few case reports in the literature. Given their sparsity, such lesions may pose a great diagnostic challenge due to varied clinical presentations and imaging features. In this study, we report the largest case series of ILP. We discuss the patient demographics, differentials, surgical approaches, and management.

Local Electronic Structure and Dynamics of Muon-Polaron Complexes in Fe_{2}O_{3}.

We perform detailed muon spin rotation (µSR) measurements in the classic antiferromagnet Fe_{2}O_{3} and explain the spectra by considering dynamic population and dissociation of charge-neutral muon-polaron complexes. We show that charge-neutral muon states in Fe_{2}O_{3}, despite lacking the signatures typical of charge-neutral muonium centers in nonmagnetic materials, have a significant impact on the measured µSR frequencies and relaxation rates. Our identification of such polaronic muon centers in Fe_{2}O_{3} suggests that isolated hydrogen (H) impurities form analogous complexes, and that H interstitials may be a source of charge carrier density in Fe_{2}O_{3}.

The interplay between oxidative stress and bioenergetic failure in neuropsychiatric illnesses: can we explain it and can we treat it?

Nitro-oxidative stress and lowered antioxidant defences play a key role in neuropsychiatric disorders such as major depression, bipolar disorder and schizophrenia. The first part of this paper details mitochondrial antioxidant mechanisms and their importance in reactive oxygen species (ROS) detoxification, including details of NO networks, the roles of H2O2 and the thioredoxin/peroxiredoxin system, and the relationship between mitochondrial respiration and NADPH production. The second part highlights and identifies the causes of the multiple pathological sequelae arising from self-amplifying increases in mitochondrial ROS production and bioenergetic failure. Particular attention is paid to NAD+ depletion as a core cause of pathology; detrimental effects of raised ROS and reactive nitrogen species on ATP and NADPH generation; detrimental effects of oxidative and nitrosative stress on the glutathione and thioredoxin systems; and the NAD+-induced signalling cascade, including the roles of SIRT1, SIRT3, PGC-1α, the FOXO family of transcription factors, Nrf1 and Nrf2. The third part discusses proposed therapeutic interventions aimed at mitigating such pathology, including the use of the NAD+ precursors nicotinamide mononucleotide and nicotinamide riboside, both of which rapidly elevate levels of NAD+ in the brain and periphery following oral administration; coenzyme Q10 which, when given with the aim of improving mitochondrial function and reducing nitro-oxidative stress in the brain, may be administered via the use of mitoquinone, which is in essence ubiquinone with an attached triphenylphosphonium cation; and N-acetylcysteine, which is associated with improved mitochondrial function in the brain and produces significant decreases in oxidative and nitrosative stress in a dose-dependent manner.

Cryopreservation of primary cultures of mammalian somatic cells in 96-well plates benefits from control of ice nucleation.

Cryopreservation of mammalian cells has to date typically been conducted in cryovials, but there are applications where cryopreservation of primary cells in multiwell plates would be advantageous. However excessive supercooling in the small volumes of liquid in each well of the multiwell plates is inevitable without intervention and tends to result in high and variable cell mortality. Here, we describe a technique for cryopreservation of adhered primary bovine granulosa cells in 96-well plates by controlled rate freezing using controlled ice nucleation. Inducing ice nucleation at warm supercooled temperatures (less than 5 °C below the melting point) during cryopreservation using a manual seeding technique significantly improved post-thaw recovery from 29.6% (SD = 8.3%) where nucleation was left uncontrolled to 57.7% (9.3%) when averaged over 8 replicate cultures (p < 0.001). Detachment of thawed cells was qualitatively observed to be more prevalent in wells which did not have ice nucleation control which suggests cryopreserved cell monolayer detachment may be a consequence of deep supercooling. Using an infra-red thermography technique we showed that many aliquots of cryoprotectant solution in 96-well plates can supercool to temperatures below -20 °C when nucleation is not controlled, and also that the freezing temperatures observed are highly variable despite stringent attempts to remove contaminants acting as nucleation sites. We conclude that successful cryopreservation of cells in 96-well plates, or any small volume format, requires control of ice nucleation.

Reaching the sustainable development goals through healthy environments: are we on track?

The adoption of the 2030 Agenda for Sustainable Development in 2015 opened new opportunities to work towards healthy environments through 'whole of government' and 'whole of society' approaches. It created a strong policy platform that acknowledges health as a result and an enabler of sustainable policies across all sectors of government. Five years into the process, an initial analysis of emerging trends indicates that, despite some encouraging developments in policy as well as overall progress in economy and technology, there remains a gap between rhetoric, ambition and reality. In particular, the monitoring system for environment and health-related sustainable development goals (SDGs) and targets requires further development; inequalities in environment and health persist and in some areas have increased; equity is not yet a central element of implementation and reporting on the achievement of the SDGs; and, most worrying of all, trends in key environmental indicators that are vital to the survival of the human species, such as those related to climate change and biodiversity, are still on an overall negative path. In summary, governments must significantly and rapidly increase action to secure the habitability and safety of planet Earth. The public health community assumes an unprecedented role in placing and maintaining health and equity at the heart of the political agenda. This demands new governance models conferring on the health sector a clear mandate and legitimacy to operate across sectors. It also requires enhancing capacities among health professionals to embrace this new level of complexity, understand the multiple links between sectoral policies and health, and successfully engage with other government sectors and stakeholders.

Influence of proportion of wheat in a pasture-based diet on milk yield, methane emissions, methane yield, and ruminal protozoa of dairy cows.

Wheat is the most common concentrate fed to grazing dairy cows in Australia, but no studies have examined the effects of wheat proportion in a pasture-based diet on milk production and methane emissions. In this 47-d experiment, 32 Holstein dairy cows were offered 1 of 4 diets during d 1 to 36. Cows in each of the dietary treatment groups were individually offered no wheat (W0) or wheat at 3 kg of dry matter (DM)/d (W3), 6 kg of DM/d (W6), or 9 kg of DM/d (W9). The remainder of the diet was 2.2 kg of DM of concentrate mix and freshly harvested perennial ryegrass (Lolium perenne) such that all individual cows were offered a total diet of approximately 20.2 kg of DM/d. From d 37 to 47 the diets of cows receiving treatments W0 and W3 remained unchanged, but cows in treatments W6 and W9 received the W3 diet. Individual cow feed intakes, milk yields, milk compositions, and methane emissions were measured for d 31 to 35 (period 1) and d 45 to 47 (period 2). During period 1, the mean intakes of cows offered the W0, W3, W6, and W9 diets were 19.2, 20.4, 20.2, and 19.8 kg of DM/d. Diet caused differences in energy-corrected milk, and means for W0, W3, W6, and W9 were 29.5, 32.4, 33.0, and 32.9 kg/d, respectively. Milk fat percentage differed with respective means of 3.93, 3.94, 3.69, and 3.17. Diets also caused differences in methane emissions, with means for W0, W3, W6, and W9 of 440, 431, 414, and 319 g/d. During period 1, the cows fed the W9 diet produced less methane and had lower methane yields (g/kg of DMI) and intensities (g/kg of energy-corrected milk) than cows fed the W3 diet. However, in period 2 when the wheat intake of cows in the W9 treatment was reduced to the same level as in the W3 treatment, their methane emissions, yields, and intensities were similar to those offered the W3 treatment, yet protozoa numbers in ruminal fluid were still much lower than those in cows offered the W3 treatment. Our research shows that for diets based on perennial ryegrass and crushed wheat, only the diet containing more than 30% crushed wheat resulted in substantially depressed milk fat concentration and reduced methane emissions, methane yield, and methane intensity. Thus, although feeding a diet with a high proportion of wheat can cause substantial methane mitigation, it can come at the cost of depression in milk fat concentration.

Transplanted human thymus slices induce and support T-cell development in mice after cryopreservation.

Nude mouse human thymus transplant model: Fresh or cryopreserved and thawed human thymus slices were transplanted subcutaneously into recipient nude mice. Nude mice subsequently produced mouse CD3+ CD4+ T-cells.

Bi-Arrhenius Diffusion and Surface Trapping of

We report measurements of the diffusion rate of isolated ion-implanted ^{8}Li^{+} within ∼120 nm of the surface of oriented single-crystal rutile TiO_{2} using a radiotracer technique. The α particles from the ^{8}Li decay provide a sensitive monitor of the distance from the surface and how the depth profile of ^{8}Li evolves with time. The main findings are that the implanted Li^{+} diffuses and traps at the (001) surface. The T dependence of the diffusivity is described by a bi-Arrhenius expression with activation energies of 0.3341(21) eV above 200 K, whereas at lower temperatures it has a much smaller barrier of 0.0313(15) eV. We consider possible origins for the surface trapping, as well the nature of the low-T barrier.

Effect of dietary fat supplementation on methane emissions from dairy cows fed wheat or corn.

Diets that contain high proportions of either wheat or supplementary fat have been individually reported to reduce enteric methane production. The objective of this research was to determine the effect of dietary fat supplementation on methane emissions and milk yield from cows fed diets containing either corn or wheat grains. It was hypothesized that cows fed a diet containing wheat would produce less methane and have lower methane yield (methane per kg of dry matter intake; MY) than cows fed a diet containing corn and that methane mitigation from fat supplementation would occur irrespective of the type of grain in the basal diet. The experiment involved 32 Holstein-Friesian dairy cows allocated to 1 of 4 treatment groups (n = 8) and individually fed different diets restricted to approximately 90% of their mean ad libitum intake measured during a covariate period. All animals were offered 11.5 kg of dry matter/d of alfalfa hay, 1.8 kg of dry matter/d of solvent-extracted canola meal, and 1 of 4 dietary supplements. Dietary supplements were 8 kg of dry matter/d of either corn or wheat, or these same treatments with the addition of 0.8 kg of canola oil. In this 5-wk experiment, d 1 to 7 served as the covariate period, d 8 to 14 as the transition period, d 15 to 28 as the adaptation period, and d 29 to 35 as the experimental period. Cows were fed their full treatment diets from d 15 to 35 during which time milk production and feed intake were measured daily. During d 29 to 35, methane production was measured for individual cows daily using the sulfur hexafluoride tracer method. The resulting averages for milk production and feed intake were analyzed by analysis of covariance with factorial grain by fat as treatment structure, animal as the unit within blocks, and the corresponding milk production or feed intake covariate averages as principal covariate. Data on milk fatty acids, ruminal fluid data on pH, ammonia, volatile fatty acids, protozoa, and methane were analyzed by ANOVA using the same treatment and blocking structures excluding the principal covariate. Cows fed a diet containing wheat had greater MY than cows fed a diet containing corn. Irrespective of the type of grain in the diet, increasing the fat concentration from 2 to 6% dry matter reduced MY. It is concluded that the grain component in the basal diet does not affect the mitigating effects of dietary fat supplements on MY.

TBX18 overexpression enhances pacemaker function in a rat subsidiary atrial pacemaker model of sick sinus syndrome.

KEY POINTS: The sinoatrial node (SAN) is the primary pacemaker of the heart. SAN dysfunction, or 'sick sinus syndrome', can cause excessively slow heart rates and pauses, leading to exercise limitation and syncope, currently treated by implantation of an electronic pacemaker. 'Biopacemaking' utilises gene therapy to restore pacemaker activity by manipulating gene expression. Overexpressing the HCN pacemaker ion channel has been widely used with limited success. We utilised bradycardic rat subsidiary atrial pacemaker tissue to evaluate alternative gene targets: the Na+ /Ca2+ exchanger NCX1, and the transcription factors TBX3 and TBX18 known to be involved in SAN embryonic development. TBX18 overexpression restored normal SAN function, as assessed by increased rate, improved heart rate stability and restoration of isoprenaline response. TBX3 and NCX1 were not effective in accelerating the rate of subsidiary atrial pacemaker tissue. Gene therapy targeting TBX18 could therefore have the potential to restore pacemaker function in human sick sinus syndrome obviating electronic pacemakers. ABSTRACT: The sinoatrial node (SAN) is the primary pacemaker of the heart. Disease of the SAN, sick sinus syndrome, causes heart rate instability in the form of bradycardia and pauses, leading to exercise limitation and syncope. Biopacemaking aims to restore pacemaker activity by manipulating gene expression, and approaches utilising HCN channel overexpression have been widely used. We evaluated alternative gene targets for biopacemaking to restore normal SAN pacemaker physiology within bradycardic subsidiary atrial pacemaker (SAP) tissue, using the Na+ /Ca2+ exchanger NCX1, and the transcription factors TBX3 and TBX18. TBX18 expression in SAP tissue restored normal SAN function, as assessed by increased rate (SAN 267.5 ± 13.6 bpm, SAP 144.1 ± 8.6 bpm, SAP-TBX18 214.4 ± 14.4 bpm; P < 0.001), improved heart rate stability (standard deviation of RR intervals fell from 39.3 ± 7.2 ms to 6.9 ± 0.8 ms, P < 0.01; root mean square of successive differences of RR intervals fell from 41.7 ± 8.2 ms to 6.1 ± 1.2 ms, P < 0.01; standard deviation of points perpendicular to the line of identity of Poincaré plots (SD1) fell from 29.5 ± 5.8 ms to 7.9 ± 2.0 ms, P < 0.05) and restoration of isoprenaline response (increases in rates of SAN 65.5 ± 1.3%, SAP 28.4 ± 3.4% and SAP-TBX18 103.3 ± 10.2%; P < 0.001). These changes were driven by a TBX18-induced switch in the dominant HCN isoform in SAP tissue, with a significant upregulation of HCN2 (from 1.01 × 10-5  ± 2.2 × 10-6 to 2.8 × 10-5  ± 4.3 × 10-6 arbitrary units, P < 0.001). Biophysically detailed computer modelling incorporating isoform-specific HCN channel electrophysiology confirmed that the measured changes in HCN abundance could account for the observed changes in beating rates. TBX3 and NCX1 were not effective in accelerating the rate of SAP tissue.

Influence of feeding supplements of almond hulls and ensiled citrus pulp on the milk production, milk composition, and methane emissions of dairy cows.

Almond hulls and citrus pulp have been fed to dairy cows with variable responses for milk production, but no information exists on their effect on enteric methane emissions. This experiment examined the effects of dietary supplementation with either almond hulls or ensiled citrus pulp on the milk yield, milk composition, and enteric methane emissions of dairy cows. Thirty-two Holstein dairy cows in mid lactation were offered 1 of 3 diets over a 28-d experiment. Twelve cows received a control (CON) diet, 10 cows a diet containing almond hulls (ALH), and 10 cows a diet containing ensiled citrus pulp (CIT). All cows were offered 6.0 kg of dry matter (DM)/d of crushed corn, 2.0 kg of DM/d of cold-pressed canola, and 0.2 kg of DM/d of a mineral mix. In addition, cows fed the CON diet were offered 14.5 kg of DM/d of alfalfa cubes; cows fed the ALH diet were offered 10.5 kg of DM/d of alfalfa cubes and 4.0 kg of DM/d of almond hulls; and cows on the CIT diet were offered 11.5 kg of DM/d of alfalfa cubes and 3.0 kg of DM/d of ensiled citrus pulp. Milk yield was measured daily and milk composition was measured on 4 d of each week. Individual cow methane emissions were measured by a sulfur hexafluoride tracer technique on d 24 to 28 of the experiment. The mean milk yield of cows fed the CON diet (27.4 kg/d) was greater than the mean milk yield of cows fed the ALH diet (24.6 kg/cow per day), whereas the mean milk yield of cows fed the CIT diet (26.2 kg/cow per day) was not different from the mean milk yield from cows fed the other 2 diets. Dietary treatment did not influence the concentrations of milk fat, protein, and lactose or fat yields, but the mean protein yield from cows fed the CON diet (0.87 kg/d) was greater than that from cows fed the ALH diet (0.78 kg/d) but not different to those fed the CIT diet (0.85 kg/d). In general, we found no differences in the proportion of individual fatty acids in milk. The mean pH of ruminal fluid from cows offered the CON diet was not different to the pH in the ruminal fluids of cows offered the ALH or the CIT diets. The mean methane emissions (g/d) and yields (g/kg of DM intake) were not influenced by dietary treatment. These findings indicate that, although almond hulls and ensiled citrus pulp can be used as a low-cost feed supplement, almond hulls did negatively affect milk production and neither inhibited enteric methane emissions.

Adaptation responses in milk fat yield and methane emissions of dairy cows when wheat was included in their diet for 16 weeks.

Short-term studies have shown that feeding dairy cows diets containing a high proportion (>40%) of wheat may result in reduced milk fat concentration and reduced CH4 emissions (g of CH4/cow per d), but no long-term studies have been done on these responses. This study compared the milk production and CH4 responses when 24 dairy cows were fed diets containing high proportions of either wheat or corn over 16 wk. Cows were assigned to 2 groups and offered a diet (CRN) containing 10.0 kg of dry matter/d of crushed corn grain, 1.8 kg of dry matter/d of canola meal, 0.2 kg of dry matter/d of minerals, and 11.0 kg of dry matter/d of chopped alfalfa hay or a similar diet (WHT) in which wheat replaced the corn. Dry matter intake and milk yields of individual cows were measured daily. Methane emissions from individual cows were measured using controlled climate respiration chambers over 2 consecutive days during each of wk 4, 10, and 16. Milk composition was measured on the 2 d when cows were in chambers during wk 4, 10, and 16. Over the 16-wk experimental period, total dry matter intake remained relatively constant and similar for the 2 dietary treatment groups. At wk 4, CH4 emission, CH4 yield (g of CH4/kg of dry matter intake), milk fat yield, and milk fat concentration were substantially less in cows fed the WHT diet compared with the same metrics in cows fed the CRN diet; but these differences were not apparent at wk 10 and 16. The responses over time in these metrics were not similar in all cows. In 4 cows fed the WHT diet, CH4 yield, milk fat concentration, and milk fat yield remained relatively constant from wk 4 to 16, whereas for 5 fed the WHT diet, their CH4 emissions, milk fat yields, and milk fat concentrations almost doubled between wk 4 and 16. In the short term (4 wk), the inclusion of approximately 45% wheat instead of corn in the diet of cows resulted in reductions of 39% in CH4 yield, 35% in milk fat concentration, and 40% in milk fat yield. However, these reductions did not persist to wk 10 or beyond. Our data indicate that cows do not all respond in the same way with some "adaptive" cows showing a marked increase in CH4 yield, milk fat concentration, and milk fat yield after wk 4, whereas in other "nonadaptive" cows, these metrics were persistently inhibited to 16 wk. This research shows that short-term studies on dietary interventions to mitigate enteric CH4 emissions may not always predict the long-term effects of such interventions.

Electrocardiographic abnormalities and mortality in aging survivors of childhood cancer: A report from the St Jude Lifetime Cohort Study.

BACKGROUND: Electrocardiography (ECG), predictive of adverse outcomes in the general population, has not been studied in cancer survivors. We evaluated the prevalence of ECG abnormalities and associations with mortality among childhood cancer survivors. METHODS: Major and minor abnormalities were coded per the Minnesota Classification system for participants in the St Jude Lifetime Cohort Study (n = 2,715) and community controls (n = 268). Odds ratios (ORs) and 95% CIs were calculated using multivariable logistic regression; and hazard ratios, using Cox proportional hazards regression. RESULTS: Survivors were a median age of 31.3 (range 18.4-63.8) years at evaluation and 7.4 (range 0-24.8) years at diagnosis. Prior therapies included cardiac-directed radiation (29.5%), anthracycline (57.9%), and alkylating (60%) chemotherapies. The prevalence of minor ECG abnormalities was similar among survivors and controls (65.2% vs 67.5%, P = .6). Major ECG abnormalities were identified in 10.7% of survivors and 4.9% of controls (P < .001). Among survivors, the most common major abnormalities were isolated ST/T wave abnormalities (7.2%), evidence of myocardial infarction (3.7%), and left ventricular hypertrophy with strain pattern (2.8%). Anthracyclines ≥300 mg/m2 (OR 1.7 95% CI 1.1-2.5) and cardiac radiation (OR 2.1 95% CI 1.5-2.9 [1-1,999 cGy], 2.6 95% CI 1.6-3.9 [2,000-2,999 cGy], 10.5 95% CI 6.5-16.9 [≥3,000 cGy]) were associated with major abnormalities. Thirteen participants had a cardiac-related death. Major abnormalities were predictive of all-cause mortality (hazard ratio 4.0 95% CI 2.1-7.8). CONCLUSIONS: Major ECG abnormalities are common among childhood cancer survivors, associated with increasing doses of anthracyclines and cardiac radiation, and predictive of both cardiac and all-cause mortality.

Viscosities encountered during the cryopreservation of dimethyl sulphoxide systems.

This study determined the viscous conditions experienced by cells in the unfrozen freeze concentrated channels between ice crystals in slow cooling protocols. This was examined for both the binary Me2SO-water and the ternary Me2SO-NaCl-water systems. Viscosity increases from 6.9 ± 0.1 mPa s at -14.4 ± 0.3 °C to 958 ± 27 mPa s at -64.3 ± 0.4 °C in the binary system, and up to 55387 ± 1068 mPa s at -75 ± 0.5 °C in the ternary (10% Me2SO, 0.9% NaCl by weight) solution were seen. This increase in viscosity limits molecular diffusion, reducing adsorption onto the crystal plane. These viscosities are significantly lower than observed in glycerol based systems and so cells in freeze concentrated channels cooled to between -60 °C and -75 °C will reside in a thick fluid not a near-solid state as is often assumed. In addition, the viscosities experienced during cooling of various Me2SO based vitrification solutions is determined to below -70 °C, as is the impact which additional solutes exert on viscosity. These data show that additional solutes in a cryopreservation system cause disproportionate increases in viscosity. This in turn impacts diffusion rates and mixing abilities of high concentrations of cryoprotectants, and have applications to understanding the fundamental cooling responses of cells to Me2SO based cryopreservation solutions.

ß-NMR Investigation of the Depth-Dependent Magnetic Properties of an Antiferromagnetic Surface.

By measuring the prototypical antiferromagnet α-Fe_{2}O_{3}, we show that it is possible to determine the static spin orientation and dynamic spin correlations within nanometers from an antiferromagnetic surface using the nuclear spin polarization of implanted ^{8}Li^{+} ions detected with ß-NMR. Remarkably, the first-order Morin spin reorientation in single crystal α-Fe_{2}O_{3} occurs at the same temperature at all depths between 1 and 100 nm from the (110) surface; however, the implanted nuclear spin experiences an increased 1/T_{1} relaxation rate at shallow depths revealing soft-surface magnons. The surface-localized dynamics decay towards the bulk with a characteristic length of ε=11±1 nm, closely matching the finite-size thresholds of hematite nanostructures.

The impact of HPV cervical screening on negative large loop excision of the transformation zone (LLETZ): A comparative cohort study.

OBJECTIVE: To determine the incidence and predictors of negative large loop excision of the transformation zone (LLETZ) following the introduction of Human Papillomavirus (HPV) cervical screening. METHOD: A retrospective cohort study. Two independent cohorts, who attended for a LLETZ procedure, before and after the introduction of HPV cervical screening were compared. For each cohort, 401 individuals were randomly selected from a colposcopy database. Clinical and colposcopic variables were extracted. The incidence of negative LLETZ was estimated in each cohort. Regression analysis was used to adjust for potential confounders and explore predictors of negative LLETZ. RESULTS: Eighty women (19.9%) from the pre-HPV testing cohort and 54 women (13.4%) from the post-HPV cohort were negative for cervical intraepithelial neoplasia (RR 0.75, CI: 0.55 to 0.93). In the post-HPV testing cohort, independent predictors of negative LLETZ were low grade cytology (RR 3.60, CI: 2.18-5.97) and a type 3 transformation zone (TZ) (RR 2.88, CI: 1.76-4.72). Women with both low grade cytology and a TZ type 3 were 10.4 times more likely to have a negative LLETZ (absolute risk 40%, 95% CI: 27-54%). CONCLUSIONS: Despite a 25% reduction in negative LLETZ following the introduction of HPV cervical screening, the incidence is still high. These results highlight the importance of continuing to improve the specificity of cervical intraepithelial neoplasia screening; this should include the use of biomarkers that detect HPV-transforming infections and techniques that sample an entirely endocervical transformation zone.

Communication: Chemisorption of muonium on gold nanoparticles: A sensitive new probe of surface magnetism and reactivity.

Chemisorption of muonium onto the surface of gold nanoparticles has been observed. Muonium (µ+e-), a light hydrogen-like atom, reacts chemically with uncapped 7 nm gold nanoparticles embedded in mesoporous silica (SBA-15) with a strong temperature-dependent rate. The addition rate is fast enough to allow coherent spin transfer into a diamagnetic muon state on the nanoparticle surface. The muon is well established as a sensitive probe of static or slowly fluctuating magnetic fields in bulk matter. These results represent the first muon spin rotation signal on a nanoparticle surface or any metallic surface. Only weak magnetic effects are seen on the surface of these Au nanoparticles consistent with Pauli paramagnetism.