Impact of body mass index on markers of vascular health in normotensive women with history of pre-eclampsia.

OBJECTIVE: Obesity and pre-eclampsia (PE) are both associated with vascular dysfunction, which translates into an increased risk for cardiovascular disease in later life. The aim of this study was to investigate whether there is an interaction between body mass index (BMI) and a history of PE in their effects on vascular health. METHODS: This was an observational case-control study of 30 women with a history of PE who were compared with 31 age- and BMI-matched controls who had an uncomplicated pregnancy. Flow-mediated dilation (FMD), carotid intima-media thickness (cIMT) and carotid distensibility (CD) were measured 6-12 months postpartum. To evaluate the impact of physical fitness, maximum oxygen uptake capacity was assessed using a standardized maximum exhaustion cycling test using breath-by-breath analysis. To specify further BMI subgroups, metabolic syndrome constituents were assessed in all individuals. RESULTS: Formerly pre-eclamptic women had significantly lower FMD (5.1 ± 2.1% vs 9.4 ± 3.4%; P < 0.01), higher cIMT (0.59 ± 0.09 vs 0.49 ± 0.07 µm; P < 0.01) and lower CD (1.54 ± 0.37%/10 mmHg vs 1.80 ± 0.39%/10 mmHg; P < 0.01) compared with controls. In our study, population BMI correlated negatively with FMD (P = 0.04) but not with cIMT or CD. BMI and PE did not exhibit an interaction effect on these vascular parameters. Physical fitness was lower in women with a history of PE and in women with higher BMI. Constituents of the metabolic syndrome, including insulin, homeostasis model assessment for insulin resistance (HOMA-ir), triglyceride, microalbuminuria and systolic and diastolic blood pressure, were significantly higher in formerly pre-eclamptic women. BMI affected glucose metabolism but not lipids or blood pressure. BMI and PE positively interacted in their effect on insulin (P = 0.04) and HOMA-ir (P = 0.02). CONCLUSIONS: Both BMI and a history of PE have negative effects on endothelial function, insulin resistance and physical fitness. In formerly pre-eclamptic women, the effect of BMI on insulin resistance was particularly high, suggesting a synergistic effect. Additionally, independently of BMI, a history of PE was associated with reduced FMD and CD and increased cIMT and blood pressure. Recognizing the cardiovascular risk profile is important for informing patients and encouraging targeted lifestyle modifications. © 2023 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Empiric antibiotic treatment for periprosthetic joint infections: a national survey in The Netherlands.

Early periprosthetic joint infection (PJI) is generally treated by means of debridement, antibiotics and implant retention (DAIR). Subsequently, empiric antibiotic therapy is commenced directly after surgery which is important for the successful treatment of PJI. The aim of this study is to evaluate current nationwide empiric antibiotic treatment regimens for PJI in the Netherlands. An electronic 15-question survey addressing the empiric antibiotic treatment strategy for PJI following THA or TKA was sent to orthopaedic surgeons in all Dutch hospitals in April 2019. Orthopaedic surgeons active in every single Dutch orthopaedic hospital (n=69) were approached. At least one surgeon in every hospital completed the survey (100% response rate). A protocol dictating the empiric antibiotic treatment following DAIR was used in 87% (60 hospitals). Among all hospitals, 72% (50 hospitals) used antibiotic monotherapy and 28% (19 hospitals) used combination therapy. Cefazolin was the most commonly used regimen in centres opting for monotherapy (42%, 29 hospitals). Similar regimens were used for the empiric treatment of suspected early PJI after revision surgery and for acute hematogenous PJI. In septic patients, combination therapy was preferred (64%). 81% (56 hospitals) incubated tissue biopsies for a minimum of 10 days whereas 16% (9 hospitals) indicated an incubation period of 7 days or less. Even in a small country such as the Netherlands there seems to be no uniformity regarding empiric antibiotic treatment for PJI. Increased uniformity regarding empiric treatment could be an important first step in improving PJI treatment.

Observation of a Quantum Phase from Classical Rotation of a Single Spin.

The theory of angular momentum connects physical rotations and quantum spins together at a fundamental level. Physical rotation of a quantum system will therefore affect fundamental quantum operations, such as spin rotations in projective Hilbert space, but these effects are subtle and experimentally challenging to observe due to the fragility of quantum coherence. We report on a measurement of a single-electron-spin phase shift arising directly from physical rotation, without transduction through magnetic fields or ancillary spins. This phase shift is observed by measuring the phase difference between a microwave driving field and a rotating two-level electron spin system, and it can accumulate nonlinearly in time. We detect the nonlinear phase using spin-echo interferometry of a single nitrogen-vacancy qubit in a diamond rotating at 200 000 rpm. Our measurements demonstrate the fundamental connections between spin, physical rotation, and quantum phase, and they will be applicable in schemes where the rotational degree of freedom of a quantum system is not fixed, such as spin-based rotation sensors and trapped nanoparticles containing spins.

Venous and autonomic function in formerly pre-eclamptic women and controls matched for body mass index.

OBJECTIVE: Prepregnancy reduced plasma volume (PV) increases the risk of subsequent pre-eclamptic pregnancy. Reduced PV is thought to reflect venous reserve capacity, especially when venous vasculature is constricted and sympathetic tone is elevated. As obesity might affect these variables, and is associated with pre-eclampsia, increased body weight may underlie these observations. The aim of this study was to determine whether the relationship between reduced venous reserve and pre-eclampsia is independent of body mass index (BMI). METHODS: This was an observational case-control study in which venous reserve capacity in 30 formerly pre-eclamptic, but currently non-pregnant, women divided equally into three groups based on BMI (BMI 19.5-24.9, 25.0-29.9 or ≥ 30.0 kg/m2 ), was compared with that in 30 healthy parous, non-pregnant controls. Cases and controls were matched for BMI, age and parity. Venous reserve capacity was quantified by assessing PV and venous compliance (VeC). The autonomic nervous system regulating venous capacitance was evaluated using heart rate (HR) variability analysis, with the women in a resting supine position and during positive head-up tilt (HUT). RESULTS: Compared with controls, formerly pre-eclamptic women had, when in a resting supine position, lower PV (1339 ± 79 vs 1547 ± 139 mL/m2 (P < 0.0001)), lower VeC (0.04 ± 0.02 vs 0.07 ± 0.02 mL/dL/mmHg (P < 0.0001)), higher sympathetic tone (1.9 ± 1.1 vs 1.2 ± 0.7 (P = 0.002)) and lower baroreceptor sensitivity (BRS; 8.7 ± 3.8 vs 19.0 ± 1.7 ms/mmHg (P < 0.0001)). During HUT, women with a history of pre-eclampsia had less modulatory capacity over VeC and BRS, while HR and sympathetic tone remained consistently higher. CONCLUSIONS: Women with a history of pre-eclampsia had reduced venous reserve capacity compared with that in BMI-matched controls. This is reflected by lower PV and VeC, with the autonomic balance being shifted towards sympathetic dominance and lower BRS. This suggests that underlying reduced venous reserve, but not BMI, relates to pre-eclampsia. Copyright © 2018 ISUOG. Published by John Wiley & Sons Ltd.

Decreased endothelial function and increased subclinical heart failure in women several years after pre-eclampsia.

OBJECTIVES: Pre-eclampsia (PE) is associated with both postpartum endothelial dysfunction and asymptomatic structural heart alterations consistent with heart failure Stage B (HF-B). In this study, we assessed the relationship between endothelial function, measured by flow-mediated dilation (FMD), and HF-B in women with a history of PE. METHODS: This was an observational study in which 67 formerly pre-eclamptic women (≥ 4 years postpartum) and 37 healthy parous controls were assessed ultrasonographically for cardiac function and geometry, as well as for endothelial function by means of brachial artery FMD. HF-B was diagnosed as left ventricular hypertrophy (left ventricular mass index (LVMi) > 95 g/m2 ), concentric remodeling (relative wall thickness > 0.42 and LVMi ≤ 95 g/m2 ), mild systolic dysfunction (left ventricular ejection fraction > 40% and < 55%) or asymptomatic valvular disease. Cardiovascular and metabolic syndrome variables were compared between women with history of PE and controls, as well as between those in the formerly pre-eclamptic group who had HF Stage A, HF-B or no HF. Logistic regression analysis was performed to assess the associations of FMD with PE, metabolic syndrome risk factors and obstetric parameters. RESULTS: The prevalence of HF-B amongst formerly pre-eclamptic women was three-fold higher than that observed for controls (25% vs 8%, P < 0.05), while FMD was lower in formerly pre-eclamptic women compared with controls (6.12% vs 8.22%, P < 0.01); history of PE remained associated independently with lower FMD after adjusting for metabolic syndrome risk factors and obstetric parameters (ß, -1.88; 95% CI, -3.59 to -0.18). However, HF-B did not relate to low FMD in formerly pre-eclamptic women. CONCLUSIONS: Years after pregnancy, formerly pre- eclamptic women have lower FMD and have HF-B more often compared with healthy parous controls. Nonetheless, HF-B was not related to reduced FMD. Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd.

Prevalence of asymptomatic heart failure in formerly pre-eclamptic women: a cohort study.

OBJECTIVES: After pre-eclampsia (PE), the prevalence of structural heart disease without symptoms, i.e. heart failure Stage B (HF-B), may be as high as one in four women in the first year postpartum. We hypothesize that a significant number of formerly pre-eclamptic women with HF-B postpartum are still in their resolving period and will not have HF-B during follow-up. METHODS: In this prospective longitudinal cohort study, we included 69 formerly pre-eclamptic women who underwent serial echocardiographic measurements at 1 and 4 years postpartum. HF-B was diagnosed as left ventricular hypertrophy (left ventricular mass index (LVMi) > 95 g/m2 ), concentric remodeling (relative wall thickness > 0.42 and LVMi ≤ 95 g/m2 ), mild systolic dysfunction (left ventricular ejection fraction > 40% and < 55%) or asymptomatic valvular disease. Women were subdivided and analyzed according to HF-B outcome: no HF-B at either visit; HF-B at first visit only; HF-B at second visit only; HF-B at both visits. RESULTS: The prevalence of HF-B in formerly pre-eclamptic women was 23% in the first year postpartum and 23% after 4 years. At the second visit, HF-B had resolved in 62.5% of affected women but was newly developed in 19% of initially unaffected women. At the first visit, 56% of women diagnosed with HF-B had reduced systolic function whereas at the second visit 69% of women with HF-B had concentric remodeling with mostly normal ejection fraction, consistent with diastolic dysfunction. CONCLUSIONS: The prevalence of HF-B can be considered consistently high (1 in 4) amongst formerly pre-eclamptic women at follow-up. Nonetheless, at an individual level, more than 60% of women found initially to be affected by HF-B will recover, whilst about 20% of formerly pre-eclamptic women with normal echocardiography in the first year postpartum will develop HF-B over the following years. Copyright © 2016 ISUOG. Published by John Wiley & Sons Ltd.

Pre-eclampsia: an important risk factor for asymptomatic heart failure.

OBJECTIVES: Pre-eclampsia (PE) is associated with both postpartum structural asymptomatic heart disease (i.e. heart failure Stage B (HF-B)) and conventional cardiovascular (CV) risk factors. We aimed to evaluate the extent to which PE, adjusted for conventional CV risk factors, is associated independently with asymptomatic cardiac abnormalities postpartum. METHODS: In this cross-sectional cohort study, 107 formerly pre-eclamptic women and 41 women with uneventful previous pregnancy (controls) were invited for CV risk assessment 4-10 years postpartum. This included cardiac ultrasound, blood pressure (BP) measurement and evaluation of metabolic syndrome determinants. Asymptomatic structural and functional cardiac abnormalities were classified as HF-B, according to the American Heart Association guidelines. Prehypertension was defined as systolic BP of 120-139 mmHg and/or diastolic BP of 80-89 mmHg. Univariate and multivariate regression analyses were performed to calculate associations of PE and conventional risk factors with HF-B. RESULTS: The prevalence of asymptomatic HF-B was approximately 3.5-fold higher in the PE group compared with controls (25% vs 7%, P < 0.01); 67% of this group had concentric remodeling and 22% had mildly impaired ejection fraction. After adjustment for postpartum interval, hypertension and high-density lipoprotein, PE was significantly associated with HF-B (adjusted odds ratio, 4.4 (95% CI, 1.0-19.1)). Moreover, in the formerly pre-eclamptic group, prehypertension was associated significantly with HF-B (odds ratio, 4.3 (95% CI, 1.4-12.7)), while metabolic syndrome determinants were not. CONCLUSION: PE is associated with a four-fold increased female-specific risk of asymptomatic cardiac abnormalities. Prehypertension apparently increases this risk significantly, while metabolic syndrome determinants do not. Copyright © 2016 ISUOG. Published by John Wiley & Sons Ltd.

Suppression of Emittance Growth Using a Shaped Cold Atom Electron and Ion Source.

We demonstrate precise control of charged particle bunch shape with a cold atom electron and ion source to create bunches with linear and, therefore, reversible Coulomb expansion. Using ultracold charged particles enables detailed observation of space-charge effects without loss of information from thermal diffusion, unambiguously demonstrating that shaping in three dimensions can result in a marked reduction of Coulomb-driven emittance growth. We show that the emittance growth suppression is accompanied by an increase in bunch focusability and brightness, improvements necessary for the development of sources capable of coherent single-shot ultrafast electron diffraction of noncrystalline objects, with applications ranging from femtosecond chemistry to materials science and rational drug design.

Past and future of the EU-habitat directive species Liparis loeselii in relation to landscape and habitat dynamics in SW-Texel, the Netherlands.

Dune slacks are important habitats, with many endangered plant species. A series of eleven dune slacks of 1-42years old was studied in SW-Texel, the Netherlands, with the EU-habitat directive species Liparis loeselii present in all except the youngest and oldest. Analysis of aerial photographs revealed that new slacks are currently formed every 4-5years. In each slack, topsoil and vegetation data were collected in 2010 and 2014-2015. During succession, vegetation changed from brackish pioneer stages to dune slacks with L. loeselii and Parnassia palustris and ultimately grassland species. Differences between dune slacks and sampling periods were mostly significant. Herb cover and soil C increased with slack age, and over the five year study period, while bare sand, bulk density and pH decreased. The annual pH-decrease was 0.055 and 0.075 for pH-H2O and pH-KCl respectively, and annual C-increase 0.16% and 35gm(-2). Liparis loeselii was only present between pHH2O 5.8-7.5 and pHKCl 5.6-7.6, and only occurred at C-content below 4.3%. In lime-poor dunes, environmental conditions thus become unsuitable approximately 34years after the start of succession. In the dune slacks, Liparis loeselii established within 6years, showed peak values after 11-16years, and declined until conditions became unsuitable. Rejuvenation may occur after large storms with fresh sand deposits. However, even with further succession, the present populations are not endangered and probably last until 2040. With new dune slacks every 5years, L. loeselii occurs in approximately eight different dune slacks at the same time, ensuring viable populations also in the future. This shows that adverse effects of succession can be counteracted by dynamics on local and landscape scale.

Increasing the Brightness of Cold Ion Beams by Suppressing Disorder-Induced Heating with Rydberg Blockade.

A model for the equilibrium coupling of an ion system with varying initial hard-sphere Rydberg blockade correlations is used to quantify the suppression of disorder-induced heating in Coulomb-expanding cold ion bunches. We show that bunches with experimentally achievable blockade parameters have an emittance reduced by a factor of 2.6 and increased focusability and brightness compared to a disordered bunch. Demonstrating suppression of disorder-induced heating is an important step in the development of techniques for the creation of beam sources with sufficient phase-space density for ultrafast, single-shot coherent diffractive imaging.

Recurrent pre-eclampsia in women with metabolic syndrome and low plasma volume: a retrospective cohort study.

OBJECTIVE: To determine the prevalence of recurrent pre-eclampsia in women with a history of pre-eclampsia with both metabolic syndrome and low plasma volume postpartum, as compared with women without either entity. DESIGN: Retrospective cohort study. SETTING: Three tertiary referral hospitals in the Netherlands. POPULATION: Women with a history of pre-eclampsia. METHODS: In 196 women with a history of pre-eclampsia we determined the presence or absence of metabolic syndrome using the World Health Organization criteria and measured plasma volume with the (125) I-human serum albumin indicator dilution technique. We compared the prevalence of recurrent pre-eclampsia in four groups, classified according to presence or absence of metabolic syndrome and low or normal plasma volume, calculating odds ratios (OR), adjusted for confounders. MAIN OUTCOME MEASURE: Recurrence of pre-eclampsia in the subsequent pregnancy. RESULTS: The prevalence of recurrent pre-eclampsia was 12% (12/99) in women without metabolic syndrome with normal plasma volume, versus 47% (8/17) in women with both metabolic syndrome and low plasma volume: OR 6.44 (95% CI 2.09-19.90), adjusted OR 7.90 (95% CI 2.30-27.16). Recurrent pre-eclampsia was present in 44% (10/23) and 25% (14/57) of women with isolated metabolic syndrome and low plasma volume, respectively. CONCLUSIONS: In the concomitant presence of metabolic syndrome and low plasma volume, the prevalence of recurrent pre-eclampsia was nearly 50%, which is four times as high as the prevalence in women without either entity. TWEETABLE ABSTRACT: Metabolic syndrome and low plasma volume raise the risk of recurrent pre-eclampsia to nearly 50%.

Chemoprophylaxis and vaccination in preventing subsequent cases of meningococcal disease in household contacts of a case of meningococcal disease: a systematic review.

Household contacts of an index case of invasive meningococcal disease (IMD) are at increased risk of acquiring disease. In revising WHO guidance on IMD in sub-Saharan Africa, a systematic review was undertaken to assess the effect of chemoprophylaxis and of vaccination in preventing subsequent cases of IMD in household contacts following an index case. A literature search for systematic reviews identified a single suitable review on chemoprophylaxis in 2004 (three studies meta-analysed). A search for primary research papers published since 2004 on chemoprophylaxis and without a date limit on vaccination was therefore undertaken. There were 2381 studies identified of which two additional studies met the inclusion criteria. The summary risk ratio for chemoprophylaxis vs. no chemoprophylaxis (four studies) in the 30-day period after a case was 0·16 [95% confidence interval (CI) 0·04-0·64, P = 0·008]; the number needed to treat to prevent one subsequent case was 200 (95% CI 111-1000). A single quasi-randomized trial assessed the role of vaccination. The risk ratio for vaccination vs. no vaccination at 30 days was 0·11 (95% CI 0·01-2·07, P = 0·14). The results support the use of chemoprophylaxis to prevent subsequent cases of IMD in household contacts of a case. Conclusions about the use of vaccination could not be drawn.

Cardiovascular disease risk is only elevated in hypertensive, formerly preeclamptic women.

OBJECTIVE: To analyse the predicted 10- and 30-year risk scores for cardiovascular disease (CVD) in patients who experienced preeclampsia (PE) 5-10 years previously compared with healthy parous controls. DESIGN: Observational study. SETTING: Tertiary referral hospital in the Netherlands. POPULATION: One hundred and fifteen patients with a history of PE and 50 controls. PE patients were categorised into two groups, hypertensive (n = 21) and normotensive (n = 94), based on use of antihypertensive medication, and next categorised into subgroups based on the onset of PE: early-onset PE (n = 39) and late-onset PE (n = 76). METHODS: All participants underwent cardiovascular risk screening 5-10 years after index pregnancy. We measured body mass, height and blood pressure. Blood was analysed for fasting glucose, insulin and lipid levels. All participants completed a validated questionnaire. The 10- and 30-year Framingham risk scores were calculated and compared. MAIN OUTCOME MEASURES: Estimated Framingham 10- and 30-year risk scores for CVD. RESULTS: The overall 10- and 30-year CVD median risks weighing subjects' lipids were comparable between formerly PE women and controls; 1.6 versus 1.5% (P = 0.22) and 9.0 versus 9.0% (P = 0.49), respectively. However, hypertensive formerly PE women have twice the CVD risk as normotensive formerly PE women: 10- and 30-year CVD median risks were 3.1 versus 1.5% (P < 0.01) and 19.0% versus 8.0% (P < 0.01), respectively. Risk estimates based on BMI rather than lipid profile show comparable results. Early-onset PE clustered more often in the hypertensive formerly PE group and showed significantly higher 10- and 30-year CVD risk estimates based on lipids compared with the late-onset PE group: 1.7 versus 1.3% (P < 0.05) and 10.0 versus 7.0% (P < 0.05), respectively. CONCLUSIONS: Women who are hypertensive after preeclampsia, have a twofold risk of developing CVD in the next 10-30 years. Formerly PE women who are normotensive in the first 10 years after their preeclamptic pregnancy have a comparable future cardiovascular risk to healthy controls.

Metabolic syndrome after pregnancies complicated by pre-eclampsia or small-for-gestational-age: a retrospective cohort.

OBJECTIVE: To study the prevalence of metabolic syndrome in women after a pregnancy complicated by pre-eclampsia or small-for-gestational-age (SGA), both epitomes of placental syndrome. DESIGN: A retrospective cohort study. SETTING: Single tertiary centre for maternal medicine in the Netherlands. POPULATION: Women with a history of pre-eclampsia in absence of SGA (n = 742) or pregnancy complicated by normotensive SGA (n = 147) between 1996 and 2010. METHODS: Women were routinely screened for underlying cardiometabolic and cardiovascular risk factors at least 6 months postpartum. Logistic regression analysis was used to calculate the odds ratio and adjusted odds ratio for each group. Adjustments were made for age, maternal height, smoking, parity, and interval between delivery and measurement. MAIN OUTCOME MEASURES: Prevalence of the metabolic syndrome. RESULTS: The prevalence of the metabolic syndrome in our population was two-fold higher for women with a history of pre-eclampsia (13.9%) compared with women with a history of SGA (7.6%). Calculated odds ratios for metabolic syndrome, fasting insulin, HOMA, and microalbuminuria were all higher for women with a history of pre-eclampsia compared with women with SGA. This difference persisted after adjustment for confounding factors: metabolic syndrome (adjusted odds ratio, aOR 2.11; 95% confidence interval, 95% CI 1.00-4.47) and hyperinsulinaemia (aOR 1.78; 95% CI 1.13-2.81) insulin resistance (HOMAIR ; aOR 1.80; 95% CI 1.14-2.86). Microalbuminuria (aOR 1.58; 95% CI 0.85-2.93) did not reach the level of significance after adjustment for confounding factors. CONCLUSIONS: A history of pre-eclampsia, rather than SGA, was associated with metabolic syndrome, suggesting that it relates to maternal rather than fetal etiology of placental syndrome.

Endorsement of ICMJE's Clinical Trial Registration Policy: a survey among journal editors.

BACKGROUND: Since 2005, the International Committee of Medical Journal Editors (ICMJE) requires researchers to prospectively register their clinical trials in a publicly accessible trial registry. The Consolidated Standards of Reporting Trials (CONSORT) statement has supported this policy since 2010. We aimed to evaluate to what extent biomedical journals have incorporated ICMJE's clinical trial registration policy into their editorial and peer review process. METHODS: We searched journals' instructions to authors and performed an internet survey among all journals publishing reports of randomised controlled trials that follow ICMJE's Recommendations for the Conduct, Reporting, Editing and Publication of Scholarly Work in Medical Journals (n = 695), and/or that endorse the CONSORT statement (n = 404) accessed in January 2011. Survey invitations were sent to the email addresses of the editorial offices and/or editors-in-chief of included journals in June 2011. RESULTS: For 757 ICMJE and/or CONSORT journals, we identified that they published RCT reports. We could assess the instructions to authors of 747 of these; 384 (51%) included a statement of requiring trial registration, and 33 (4%) recommended this. We invited 692 editorial offices for our survey; 253 (37%) responded, of which 50% indicated that trial registration was required; 18% cross-checked submitted papers against registered records to identify discrepancies; 67% would consider retrospectively registered studies for publication. Survey responses and specifications in instructions to authors were often discordant. CONCLUSION: At least half of the responding journals did not adhere to ICMJE's trial registration policy. Registration should be further promoted among authors, editors and peer reviewers.

Detailed observation of space-charge dynamics using ultracold ion bunches.

Control of Coulomb expansion in charged particle beams is of critical importance for applications including electron and ion microscopy, injectors for particle accelerators and in ultrafast electron diffraction, where space-charge effects constrain the temporal and spatial imaging resolution. The development of techniques to reverse space-charge-driven expansion, or to observe shock waves and other striking phenomena, have been limited by the masking effect of thermal diffusion. Here we show that ultracold ion bunches extracted from laser-cooled atoms can be used to observe the effects of self-interactions with unprecedented detail. We generate arrays of small closely spaced ion bunches that interact to form complex and surprising patterns. We also show that nanosecond cold ion bunches provide data for analogous ultrafast electron systems, where the dynamics occur on timescales too short for detailed observation. In a surprising twist, slow atoms may underpin progress in high-energy and ultrafast physics.

Treatment and prognostic factors of radiation-associated angiosarcoma (RAAS) after primary breast cancer: a systematic review.

BACKGROUND: Radiation-associated angiosarcoma (RAAS) of the breast is a rare, aggressive disease. The incidence is increasing with the prolonged survival of women irradiated for primary breast cancer. Surgery is the current treatment of choice. Prognosis is poor. This review aims to evaluate all publications on primary treatment of RAAS to identify prognostic factors and evaluate treatment modalities. METHODS: Databases were searched for articles with published individual patient data on prognostic factors, treatment and follow-up of patients with RAAS. A regression analysis was performed to test the prognostic values of age, interval between primary treatment and RAAS, tumour size and grade on the local recurrence-free interval (LRFI) and overall survival (OS). The effects of treatment modalities surgery, radiation (with or without hyperthermia) and chemotherapy or combinations were evaluated. RESULTS: 74 articles were included, representing data on 222 patients. In these patients, the 5-year OS was 43% and 5-year LRFI was 32%. Tumour size and age were significant prognostic factors on LRFI and OS. Of all patients, 68% received surgery alone, 17% surgery and reirradiation and 6% surgery with chemotherapy. The remaining 9% received primary treatments without surgery. Surgery with radiotherapy had a better 5-year LRFI of 57% compared to 34% for surgery alone (p=0.008). The value of other treatment modalities could not be assessed. CONCLUSIONS: This systematic review confirms the poor prognosis of RAAS. Tumour size and age were of prognostic value. The addition of reirradiation to surgery in the treatment of RAAS appears to enhance local control.

Menstrual blood closely resembles the uterine immune micro-environment and is clearly distinct from peripheral blood.

STUDY QUESTION: Is menstrual blood a suitable source of endometrial derived lymphocytes? SUMMARY ANSWER: Mononuclear cells isolated from menstrual samples (menstrual blood mononuclear cells (MMC)) are clearly distinct from peripheral blood mononuclear cells (PBMC) and show a strong resemblance with biopsy-derived endometrial mononuclear cells. WHAT IS KNOWN ALREADY: A critical event in the onset of pregnancy is the implantation of the embryo in the uterine wall. The immune cell composition in the endometrium at the time of implantation is considered pivotal for success. Despite advancing knowledge on the composition of the immune cell population in the uterus, the role of endometrial immune cells in reproductive disorders is still not fully resolved, mainly due to the fact that this type of research requires invasive techniques. Here, we collected menstrual fluid and validated this unique non-invasive technique to obtain and study the endometrium-derived immune cells which would be present around the time of implantation. STUDY DESIGN, SIZE, DURATION: Five healthy non-pregnant females with regular menstruation cycles and not using oral contraceptives collected their menstrual blood using a menstrual cup in five consecutive cycles. Sampling took place over the first 3 days of menses, with 12 h intervals. Peripheral blood samples, taken before and after each menstruation, were obtained for comparative analysis. PARTICIPANTS/MATERIALS, SETTING, METHODS: MMC and PBMC samples were characterized for the different lymphocyte subsets by flow cytometry, with emphasis on NK cells and T cells. Next, the functional capacity of the MMC-derived NK cells was determined by measuring intracellular production of IFN-γ, granzyme B and perforin after culture in the presence of IL-2 and IL-15. MAIN RESULTS AND THE ROLE OF CHANCE: In support of their endometrial origin, MMC samples contained the typical composition of mononuclear cells expected of endometrial tissue, were phenotypically similar to the reported phenotype for biopsy-derived endometrial cells, and were distinct from PBMC. Increased percentages of NK cells and decreased percentages of T cells were found in MMC when compared with PBMC from the same female. The MMC-derived NK cells were pre-dominantly CD56(bright)/CD16(-), in contrast to the primarily CD56(dim)/CD16(+) peripheral blood NK cells. MMC-derived NK cells expressed CD103, indicating their mucosal origin. In addition, the pattern of natural cytotoxicity receptor (NCR) expression in MMC-derived NK cells was comparable with that in endometrial biopsy-derived NK cells. Compared with PBMC, the NKp30 expression was decreased, while the percentage of NKp44 positive cells was increased in MMC samples. CXCR3 and CXCR4 were hardly expressed by MMC-derived NK cells, indicating that these cells are not of PBMC origin. NK cells from MMC samples were functional as shown by their capacity to produce IFN-γ, granzyme B and perforin, upon stimulation with IL-2 and IL-15. MMC-derived T cells revealed an increased expression of CD103, CD69 and CXCR4 compared with PBMC-derived T cells. Importantly, MMC collection using a menstrual cup proved highly reliable and reproducible between women and between cycles. LIMITATIONS, REASONS FOR CAUTION: Based on the parameters we studied, MMC appear similar to biopsy-derived endometrial mononuclear cells. However, sampling is not done at the exact same time in the menstrual cycle, and thus we cannot exclude some, as yet undetected, differences. Also, it should be considered that for some women, the use of the menstrual cup may be unpleasant. WIDER IMPLICATIONS OF THE FINDINGS: Menstrual blood may be a source of endometrial cells and may create new opportunities to study uterine immunological cells in fertility issues. STUDY FUNDING/COMPETING INTEREST(S): No external funding was obtained for the present study. None of the authors have any conflict of interest to declare. TRIAL REGISTRATION NUMBER: NA.

The incidence of mild and severe hypoglycaemia in patients with type 2 diabetes mellitus treated with sulfonylureas: a systematic review and meta-analysis.

Patients with type 2 diabetes mellitus using sulfonylurea derivatives or insulin may experience hypoglycaemia. However, recent data regarding the incidence of hypoglycaemia are scarce. We conducted a systematic review and meta-analysis to determine the proportion of patients with type 2 diabetes mellitus that experience hypoglycaemia when treated with sulfonylurea or insulin. We searched MEDLINE and EMBASE for randomized controlled trials that compared incretin-based drugs to sulfonylureas or insulin and assessed hypoglycaemia incidence in the latter therapies. Subgroup and meta-regression analyses were performed to study possible associations with potential risk factors for hypoglycaemia. Data of 25 studies were extracted, 22 for sulfonylurea and 3 for insulin. Hypoglycaemia with glucose ≤3.1 mmol/L or ≤2.8 mmol/L was experienced by 10.1% [95% confidence interval (CI) 7.3-13.8%] and 5.9% (95% CI 2.5-13.4%) of patients with any sulfonylurea treatment. Severe hypoglycaemia was experienced by 0.8% (95% CI 0.5-1.3%) of patients. Hypoglycaemia with glucose ≤3.1 mmol/L and severe hypoglycaemia occurred least frequently with gliclazide: in 1.4% (95% CI 0.8-2.4%) and 0.1% (95% CI 0-0.7%) of patients, respectively. None of the risk factors were significant in a stepwise multivariate meta-regression analysis. Too few studies had insulin as comparator, so these data could not be meta-analysed. The majority of patients with type 2 diabetes mellitus on sulfonylurea therapy in clinical trials remain free of any relevant hypoglycaemia. Gliclazide was associated with the lowest risk of hypoglycaemia. Because participants in randomized controlled trials differ from the general population, care should be taken when translating these data into clinical practice.

High-coherence picosecond electron bunches from cold atoms.

Ultrafast electron diffraction enables the study of molecular structural dynamics with atomic resolution at subpicosecond timescales, with applications in solid-state physics and rational drug design. Progress with ultrafast electron diffraction has been constrained by the limited transverse coherence of high-current electron sources. Photoionization of laser-cooled atoms can produce electrons of intrinsically high coherence, but has been too slow for ultrafast electron diffraction. Ionization with femtosecond lasers should in principle reduce the electron pulse duration, but the high bandwidth inherent to short laser pulses is expected to destroy the transverse coherence. Here we demonstrate that a two-colour process with femtosecond excitation followed by nanosecond photoionization can produce picosecond electron bunches with high transverse coherence. Ultimately, the unique combination of ultrafast ionization, high coherence and three-dimensional bunch shaping capabilities of cold atom electron sources have the potential for realising the brightness and coherence requirements for single-shot electron diffraction from crystalline biological samples.