An ultra-high-stability four-axis ultra-high-vacuum sample manipulator.

A report on a four-axis ultra-high-stability manipulator developed for use at the Veritas and Species RIXS beamlines at MAX IV Laboratory, Lund, Sweden, is presented. The manipulator consists of a compact, light-weight X-Y table with a stiffened Z tower carrying a platform with a rotary seal to which a manipulator rod holding the sample can be attached. Its design parameters have been optimized to achieve high eigen-frequencies via a light-weight yet stiff construction, to absorb forces without deformations, provide a low center of gravity, and have a compact footprint without compromising access to the manipulator rod. The manipulator system can house a multitude of different, easily exchangeable, manipulator rods that can be tailor-made for specific experimental requirements without having to rebuild the entire sample positioning system. It is shown that the manipulator has its lowest eigen-frequency at 48.5 Hz and that long-term stability is in the few tens of nanometres. Position accuracy is shown to be better than 100 nm. Angular accuracy is in the 500 nrad range with a long-term stability of a few hundred nanoradians.

Understanding the mechanical limitations of the performance of soft X-ray monochromators at MAX IV laboratory.

MAX IV is a fourth-generation, or diffraction-limited, synchrotron light source with a number of state-of-the-art beamlines. The performance of a beamline is, to a high degree, set by the energy resolution it can achieve, which in turn is governed to a large extent by the monochromator. During the design phase of a monochromator, the mechanical requirements must be fully understood and met with margin. During commissioning, the performance must be verified and optimized. In this paper, six soft X-ray monochromators at MAX IV beamlines (Bloch, Veritas, HIPPIE, SPECIES, FinEstBeAMS and SoftiMAX) are examined with a focus on their resolving power, energy range and the time required to change measurement range, as those parameters are dependent on each other. The monochromators have a modern commercial design, planned and developed in close collaboration with the vendors. This paper aims to present the current status of the commissioning at MAX IV with emphasis on elucidating the mechanical limitations on the performance of the monochromators. It contains analysis of the outcome and our approach to achieve fast and high-resolution monochromators.

A five-axis parallel kinematic mirror unit for soft X-ray beamlines at MAX†IV.

With the introduction of the multi-bend achromats in the new fourth-generation storage rings the emittance has decreased by an order of magnitude resulting in increased brightness. However, the higher brightness comes with smaller beam sizes and narrower radiation cones. As a consequence, the requirements on mechanical stability regarding the beamline components increases. Here an innovative five-axis parallel kinematic mirror unit for use with soft X-ray beamlines using off-axis grazing-incidence optics is presented. Using simulations and measurements from the HIPPIE beamline at the MAX IV Laboratory it is shown that it has no Eigen frequencies below 90 Hz. Its positioning accuracy is better than 25 nm linearly and 17-35 µrad angularly depending on the mirror chamber dimensions.

Overweight and obesity impair left ventricular systolic function as measured by left ventricular ejection fraction and global longitudinal strain.

AIMS: Obesity is associated with type 2 diabetes mellitus, left ventricular diastolic dysfunction and heart failure but it is unclear to which extent it is related to left ventricular systolic dysfunction. The aim of the study was to explore the effects of overweight and obesity on left ventricular systolic function in patients with type 2 diabetes mellitus and a control group of non-diabetic persons. METHODS: We prospectively investigated 384 patients with type 2 diabetes mellitus, and 184 controls who participated in the CARDIPP and CAREFUL studies. The participants were grouped according to body mass index (normal weight < 25 kg/m2, overweight 25-29 kg/m2, and obesity ≥ 30 kg/m2). Echocardiography was performed at the beginning of the study and after 4-years in the patient group. RESULTS: Univariable and multivariable regression analysis revealed that variations in left ventricular ejection fraction, global longitudinal strain, left ventricular mass and diastolic function expressed as E/é (the ratio between early diastolic mitral flow and annular motion velocities) all are related to body mass index. The mean and standard deviation of left ventricular ejection fraction and global longitudinal strain values were 57% (8%) vs. - 18.6% (2.3%) for normal weight patients, 53% (8%) vs. - 17.5% (2.3%) for overweight, and 49% (9%) vs. - 16.2% (3.0%) for obese (p < 0.05 vs. p < 0.05). Corresponding results in the control group were 58% (6%) vs. - 22.3% (3.0%), 55% (7%) vs. - 20.8% (3.1%) and 54% (8%) - 19.6% (4.0%) (p < 0.05 vs. p < 0.05). Patients who gained weight from baseline to follow-up changed left ventricular ejection fraction (median and interquartile range) by - 1.0 (9.0) % (n = 187) and patients who lost weight changed left ventricular ejection fraction by 1.0 (10.0) % (n = 179) (p < 0.05). CONCLUSION: Overweight and obesity impair left ventricular ejection fraction and global longitudinal strain in both patients with type 2 diabetes mellitus and non-diabetic persons. Trial registration ClinicalTrials.gov identifier NCT 01049737.

The SPECIES beamline at the MAX IV Laboratory: a facility for soft X-ray RIXS and APXPS.

SPECIES is an undulator-based soft X-ray beamline that replaced the old I511 beamline at the MAX II storage ring. SPECIES is aimed at high-resolution ambient-pressure X-ray photoelectron spectroscopy (APXPS), near-edge X-ray absorption fine-structure (NEXAFS), X-ray emission spectroscopy (XES) and resonant inelastic X-ray scattering (RIXS) experiments. The beamline has two branches that use a common elliptically polarizing undulator and monochromator. The beam is switched between the two branches by changing the focusing optics after the monochromator. Both branches have separate exit slits, refocusing optics and dedicated permanent endstations. This allows very fast switching between two types of experiments and offers a unique combination of the surface-sensitive XPS and bulk-sensitive RIXS techniques both in UHV and at elevated ambient-pressure conditions on a single beamline. Another unique property of the beamline is that it reaches energies down to approximately 27 eV, which is not obtainable on other current APXPS beamlines. This allows, for instance, valence band studies under ambient-pressure conditions. In this article the main properties and performance of the beamline are presented, together with selected showcase experiments performed on the new setup.

Using anti-Müllerian hormone to identify a good prognosis group in women of advanced reproductive age.

BACKGROUND: The probability of pregnancy after in vitro fertilisation (IVF) declines with age in parallel with a reduction in the ovarian reserve. However, there is considerable variation in the ovarian reserve in women of advanced reproductive age; so to give such women accurate advice about the prospects of treatment success, factors other than age must be considered. Anti-Müllerian hormone (AMH) has been shown to be a good indicator of ovarian reserve, and its utility is explored in this paper. AIMS: To determine the utility of AMH serum levels for prediction of ovarian response to gonadotropin stimulation and outcome in IVF in women of advanced reproductive age. METHODS: The material consists of 127 women with a median age of 42 years (range 39-46) having had their first cycle of IVF/intracytoplasmic sperm injection (ICSI) treatment from November 2006 to December 2008. During this period, a total of 772 oocyte retrievals and 715 embryo transfers were performed at the clinic (median age 36.4 years). AMH was analysed with the Beckman Coulter DSL ELISA. Agonist and antagonist protocols were used and monitored by ultrasound and oestradiol; embryo transfer was performed on day 2, 3 or 5 of culture. RESULTS: The lower the AMH, the higher the risk of cycle cancellation, low oocyte yield and treatment failure. Women with a serum AMH above 8.6 pmol/L had a good chance of achieving live birth after IVF/ICSI treatment. CONCLUSIONS: Anti-Müllerian hormone is useful for identifying a good prognosis group in women of advanced reproductive age.

Embryo transfer is equally effective at cleavage stage and blastocyst stage: a randomized prospective study.

OBJECTIVE: To compare the implantation and pregnancy rates after cleavage stage embryo transfer (ET) with transfer of blastocyst-stage (days 5-6) embryos. STUDY DESIGN: Prospective randomized trial at an assisted reproduction unit in a university hospital. Women with six or more follicles at the last ultrasound scan before oocyte aspiration were randomized for transfer of a maximum of two embryos after 2-3 days (n = 80) or after 5-6 days (n = 64) of culture. Embryo quality, implantation and pregnancy rates were evaluated. Statistical significance was tested with the Chi-square test and Fisher's exact test. RESULT(S): No significant difference was observed in implantation rates (21.1% versus 20.9%, respectively) and clinical pregnancy rates (36.7% versus 32.5% respectively) after blastocyst and cleavage stage transfers for the two groups. The pregnancy rate among subjects who had at least one good quality embryo transferred was 37.5% per day 2-3 ET and 60% per day 5-6 ET. CONCLUSION(S): The overall implantation and pregnancy rates after embryo transfer at cleavage stage and at blastocyst stage transfer were not statistically different. Women who had at least one good quality blastocyst (n = 25) had a high pregnancy rate (60% per ET). Blastocyst transfer is a good alternative for couples with many good quality embryos on day 2 after insemination.

Can diabetes medication be reduced in elderly patients? An observational study of diabetes drug withdrawal in nursing home patients with tight glycaemic control.

AIM: To explore the feasibility of withdrawal of diabetes medication in elderly patients with HbA1c

Metformin versus oral contraceptive pill in polycystic ovary syndrome: a Cochrane review.

BACKGROUND: The object of this review was to compare metformin versus oral contraceptive pill (OCP) treatment in polycystic ovary syndrome. METHODS: A systematic review and meta-analysis employing the principles of the Cochrane Menstrual Disorders and Subfertility Group was undertaken. RESULTS: Four randomized controlled trials (RCTs) (104 subjects) were included. Limited data demonstrated no evidence of a difference in effect between metformin and the OCP on hirsutism, acne or development of type 2 diabetes mellitus. There were no trials assessing diagnosis of cardiovascular disease or endometrial cancer. Metformin, in comparison with the OCP, was less effective in improving menstrual pattern [Peto odds ratio (OR) 0.08, 95% confidence interval (CI) 0.01-0.45) and in reducing the serum total testosterone level weighted mean difference (WMD) 0.54, 95% CI 0.22-0.86] but more effective in reducing fasting insulin (WMD -3.46, 95% CI - 5.39 to -1.52) and not increasing fasting triglyceride (WMD -0.48, 95% CI - 0.86 to -0.09) levels. Limited data demonstrated no evidence of a difference in effect between the two therapies on reducing fasting glucose or total cholesterol levels and severe adverse events. CONCLUSIONS: The limited RCT evidence to date does not show adverse metabolic risk with the use of the OCP compared with metformin. Further long-term RCTs are required.

Prediction of embryo developmental potential and pregnancy based on early stage morphological characteristics.

OBJECTIVE: To analyze the association between morphological details at different stages of culture with blastocyst development, with an aim to improve selection for transfer. DESIGN: Retrospective audit of data. SETTING: Tertiary referral center and university hospital. PATIENT(S): Two hundred sixty-eight couples underwent 357 treatment cycles. INTERVENTION(S): Oocyte pickups for IVF or intracytoplasmic sperm injection (ICSI) after ovarian stimulation. Embryos were individually cultured and examined on days 0-2 for morphological details and developmental characteristics, and selected for transfer, freezing, or further culture. MAIN OUTCOME MEASURES: The association of blastocyst development and pregnancy with morphological characteristics. RESULT(S): Five morphological characteristics (appearance of the cytoplasm, pronuclei and nucleoli, cytoplasmic deficit, and developmental rate) showed the strongest association with blastocyst development. By combining information from all days of culture into a cumulative score, prediction was greatly improved, compared to only using day 2 morphology. Cytoplasmic dysmorphisms of the oocyte, including accumulation of smooth endoplasmic reticulum, were associated with poor developmental performance. Differential weighting of these characteristics was included in a new embryo scoring system, which showed a strong correlation with implantation. CONCLUSION(S): Weighting individual morphological characteristics of zygotes and embryos and combining them into a cumulative embryo score can improve selection of embryos for transfer.

Power doppler ultrasound assessment of the relationship between age and ovarian perifollicular blood flow in women undergoing in vitro fertilization treatment.

PURPOSE: To examine the relationship between age and ovarian perifollicular blood flow (PFBF) in women undergoing IVF. METHODS: Serial transvaginal power Doppler ultrasound (PDU) scans to assess ovarian PFBF were performed prospectively throughout the follicular phase of ovarian stimulation in women undergoing IVF. The ultrasound assessment days were categorized according to day of hCG trigger. RESULTS: A total of 1050 ovarian follicles from 34 women undergoing one IVF treatment cycle were used for data analysis. The median age of the women was 38.5 years, ranging from 28 years to 44 years. There was a significant negative correlation between age and ovarian PFBF on the day of hCG trigger or trigger day minus 1, but not beforehand during the follicular phase. CONCLUSIONS: There was a significant negative correlation between age and ovarian PFBF in women undergoing IVF which was only observed very late in the follicular phase of ovarian stimulation.

Power Doppler ultrasound assessment of ovarian perifollicular blood flow in women with polycystic ovaries and normal ovaries during in vitro fertilization treatment.

OBJECTIVE: To evaluate whether ovarian perifollicular blood flow (PFBF) varies by ultrasound among women with polycystic and normal ovaries undergoing in vitro fertilization (IVF). DESIGN: Prospective observational cohort study of women undergoing IVF treatment. SETTING: Department of reproductive medicine at a university teaching hospital. PATIENT(S): Thirty four women with regular spontaneous ovulatory menstrual cycles undergoing IVF divided into two groups according to findings on a baseline transvaginal ultrasound scan: group 1 consisted of 20 women with ultrasound-evident normal ovaries (USNO group), and group 2 consisted of 14 women with ultrasound-evident polycystic ovaries (USPCO group). INTERVENTION(S): Serial transvaginal power Doppler ultrasound assessments throughout the follicular phase of ovarian stimulation. MAIN OUTCOME MEASURE(S): Ovarian PFBF and ovarian stromal artery pulsatility index. RESULT(S): Women with USPCO had a significantly lower ovarian stromal artery pulsatility index at the time of the first ultrasound assessment before starting the FSH injections compared with USNO women. However, there was no difference in ovarian PFBF between women with USPCO and USNO during the follicular phase of ovarian stimulation for IVF. CONCLUSION(S): There is no difference in ovarian follicular vascularity between women with polycystic and normal ovaries during ovarian stimulation at IVF treatment.

No decline in semen quality among potential sperm donors in Sydney, Australia, between 1983 and 2001.

PURPOSE: To determine whether the quality of semen has changed over time in men screened for semen donation. METHODS: All 448 men volunteering for semen donation between 1983 and 2001 at a donor insemination clinic in Sydney, Australia, were included in this longitudinal single centre observational analysis of semen parameters. There was no selection for fertility or marital status but all volunteers had to be aged between 18 and 40 years. RESULTS: There was no change in the total sperm count during the study period (r = 0.065, P = 0.17) using a linear regression model. The ejaculate volume did not change (r = 0.002, P = 0.97), while an increase in sperm motility was seen (Spearman R = 0.194, P < 0.001). CONCLUSION: The semen quality of volunteers for sperm donation presenting to our donor insemination clinic in Sydney between 1983 and 2001 has not declined.

Hormone replacement therapy after a diagnosis of breast cancer: cancer recurrence and mortality.

OBJECTIVE: To determine whether hormone replacement therapy (HRT) after treatment for breast cancer is associated with increased risk of recurrence and mortality. DESIGN: Retrospective observational study. PARTICIPANTS AND SETTING: Postmenopausal women diagnosed with breast cancer and treated by five Sydney doctors between 1964 and 1999. OUTCOME MEASURES: Times from diagnosis to cancer recurrence or new breast cancer, to death from all causes and to death from primary tumour were compared between women who used HRT for menopausal symptoms after diagnosis and those who did not. Relative risks (RRs) were determined from Cox regression analyses, adjusted for patient and tumour characteristics. RESULTS: 1122 women were followed up for 0-36 years (median, 6.08 years); 154 were lost to follow-up. 286 women used HRT for menopausal symptoms for up to 26 years (median, 1.75 years). Compared with non-users, HRT users had reduced risk of cancer recurrence (adjusted relative risk [RR], 0.62; 95% CI, 0.43-0.87), all-cause mortality (RR, 0.34; 95% CI, 0.19-0.59) and death from primary tumour (RR, 0.40; 95% CI, 0.22-0.72). Continuous combined HRT was associated with a reduced risk of death from primary tumour (RR, 0.32; 95% CI, 0.12-0.88) and all-cause mortality (RR, 0.27; 95% CI, 0.10-0.73). CONCLUSION: HRT use for menopausal symptoms by women treated for primary invasive breast cancer is not associated with an increased risk of breast cancer recurrence or shortened life expectancy.

Predictive value of mid luteal progesterone concentration before luteal support in controlled ovarian hyperstimulation with intrauterine insemination.

BACKGROUND: There is no published data assessing whether higher mid luteal serum progesterone (P4) levels are associated with a higher cycle pregnancy rate (CPR) in controlled ovarian hyperstimulation (COH) with intrauterine insemination (IUI). AIMS: To assess whether the mid luteal serum P4 level is predictive of pregnancy in COH with IUI. METHODS: A retrospective cohort study of all women with unexplained, minimal endometriosis or mild male factor infertility who underwent COH with IUI between October 1999 and December 2000 at our department was analysed. The COH was achieved with follicle stimulating hormone injections. All cycles were triggered with human chorionic gonadotropin when at least one follicle > or =15 mm was visible on ultrasound and IUI performed the following day. A serum P4 and beta human chorionic gonadotropin level was measured at 7 and 14 days post-trigger, respectively. RESULTS: There were 33 pregnancies in the 188 cycles analysed, giving a CPR of 18%. The median (range) mid luteal P4 level for all cycles was 51 nmol/L (1.8-234). This did not differ between the pregnant (55 nmol/L) and non-pregnant (50 nmol/L) cycles (P=0.282, Mann-Whitney U-test). There was also no difference in CPR between cohorts below or above the cut-off levels of 33 nmol/L (25th percentile) (13.3 vs 18.9%; P=0.39), 51 nmol/L (50th percentile) (16.0 vs 19.1%; P=0.57), or 69 nmol/L (75th percentile) (16.3 vs 21.3%; P=0.44), respectively. CONCLUSIONS: Increased mid luteal serum P4 levels are not associated with a higher CPR in women undergoing COH with IUI. However, a low mid luteal P4 level < or =25 nmol/L may help predict treatment failure.