Patient-reported experience with hypoglossal nerve stimulation in the treatment of obstructive sleep apnea.

BACKGROUND: Breathing-synchronized hypoglossal nerve stimulation (HNS) is routinely used as an alternative treatment for patients with obstructive sleep apnea (OSA). Significant and clinically relevant improvements in disease severity and OSA symptoms such as daytime sleepiness as well as overall quality of life have been reported in randomized-controlled trials and large real-world cohort studies. However, so far, few data exist on patient-reported experience with the treatment. METHODS: A structured survey with 22 questions was constructed using five-level Likert scales (1 = no agreement, 5 = complete agreement) to evaluate patient experience with HNS and perception of the treatment in the domains "Overall experience with therapy," "Experience with treatment process," and "Side-effects from treatment." Additional data were collected on current symptom status, measured with Epworth sleepiness scale (ESS) questionnaire, and OSA disease history. Multiple linear regression analysis was conducted to test associations of medical variables and response behavior. Correlations between variables and domains, as well as individual items, were assessed using Spearman rank test. RESULTS: A total of 75 patients from Germany who were treated with breathing-synchronized HNS were enrolled (mean age 57.3 years, 78% male), and 71 questionnaires with complete data were included for analysis. Two-thirds of participants (67%) had a history of OSA history for 5 years or longer. Of all patients, 76% had normalized OSA symptoms at time of the study (ESS: 6.4 ± 5.0) and 98% reported using stimulation therapy every night. Regression analysis revealed an association of current symptoms measured with ESS and response behavior. Hence, patients with normalized daytime sleepiness reported significantly more positive experience across all domains assessed, compared to patients with residual daytime sleepiness. Overall, only 2% of participants reported side effects that made them reduce or discontinue stimulation therapy. The rate of reported side effects was associated with current symptom control under therapy. CONCLUSIONS: Overall patient-reported experience with breathing-synchronized HNS therapy was positive and high satisfaction with the treatment process was observed. Side effects occurred, but rarely affected subjective use of the therapy or satisfaction. Subjective experience and perception are influenced by residual daytime sleepiness with stimulation therapy.

Nab-paclitaxel weekly versus dose-dense solvent-based paclitaxel followed by dose-dense epirubicin plus cyclophosphamide in high-risk HR+/HER2- early breast cancer: results from the neoadjuvant part of the WSG-ADAPT-HR+/HER2- trial.

BACKGROUND: In high-risk hormone receptor-positive/human epidermal growth factor receptor 2-negative (HR+/HER2-) early breast cancer (EBC), nanoparticle albumin-bound (nab)-paclitaxel showed promising efficacy versus solvent-based (sb)-paclitaxel in neoadjuvant trials; however, optimal patient and therapy selection remains a topic of ongoing research. Here, we investigate the potential of Oncotype DX® recurrence score (RS) and endocrine therapy (ET) response (low post-endocrine Ki67) for therapy selection. PATIENTS AND METHODS: Within the WSG-ADAPT trial (NCT01779206), high-risk HR+/HER2- EBC patients were randomized to (neo)adjuvant 4× sb-paclitaxel 175 mg/m2 q2w or 8× nab-paclitaxel 125 mg/m2 q1w, followed by 4× epirubicin + cyclophosphamide (90 mg + 600 mg) q2w; inclusion criteria: (i) cN0-1, RS 12-25, and post-ET Ki67 >10%; (ii) cN0-1 with RS >25. Patients with cN2-3 or (G3, baseline Ki67 ≥40%, and tumor size >1 cm) were allowed to be included without RS and/or ET response testing. Associations of key factors with pathological complete response (pCR) (primary) and survival (secondary) endpoints were analyzed using statistical mediation and moderation models. RESULTS: Eight hundred and sixty-four patients received neoadjuvant nab-paclitaxel (n= 437) or sb-paclitaxel (n = 427); nab-paclitaxel was superior for pCR (20.8% versus 12.9%, P = 0.002). pCR was higher for RS >25 versus RS ≤25 (16.0% versus 8.4%, P = 0.021) and for ET non-response versus ET response (15.1% versus 6.0%, P = 0.027); no factors were predictive for the relative efficacy of nab-paclitaxel versus sb-paclitaxel. Patients with pCR had longer distant disease-free survival [dDFS; hazard ratio 0.42, 95% confidence interval (CI) 0.20-0.91, P = 0.024]. Despite favorable prognostic association of RS >25 versus RS ≤25 with pCR (odds ratio 3.11, 95% CI 1.71-5.63, P ≤ 0.001), higher RS was unfavorably associated with dDFS (hazard ratio 1.03, 95% CI 1.01-1.05, P = 0.010). CONCLUSIONS: In high-risk HR+/HER2- EBC, neoadjuvant nab-paclitaxel q1w appears superior to sb-paclitaxel q2w regarding pCR. Combining RS and ET response assessment appears to select patients with highest pCR rates. The disadvantage of higher RS for dDFS is reduced in patients with pCR. These are the first results from a large neoadjuvant randomized trial supporting the use of RS to help select patients for neoadjuvant chemotherapy in high-risk HR+/HER2- EBC.

Functional MRI in neuro-urology: A narrative review.

Neuro-imaging has given urologists a new tool to investigate the neural control of the lower urinary tract. Using functional magnetic resonance imaging (fMRI), it is now possible to understand which areas of the brain contribute to the proper function of the storage and voiding of the lower urinary tract. This field of research has evolved from simple anatomical descriptions to elucidating the complex micturition network. A keyword search of the Medline database was conducted by two reviewers for relevant studies from January 1, 2010, to August 2022. Of 2047 peer-reviewed articles, 49 are included in this review. In the last decade, a detailed understanding of the brain-bladder network has been described, elucidating a dedicated network, as well as activated areas in the brainstem, cerebellum, and cortex that share reproducible connectivity patterns. Research has shown that various urological diseases can lead to specific changes in this network and that therapies used by urologists to treat lower urinary tract symptoms (LUTS) are also able to modify neuronal activity. This represents a set of potential new therapeutic targets for the management of the lower urinary tract symptoms (LUTS). fMRI technology has made it possible to identify subgroups of responders to various treatments (biofeedback, anticholinergic, neuromodulation) and predict favourable outcomes. Lastly, this breakthrough understanding of neural control over bladder function has led to treatments that directly target brain regions of interest to improve LUTS. One such example is the use of non-invasive transcranial neuromodulation to improve voiding symptoms in individuals with multiple sclerosis.

Neoadjuvant durvalumab improves survival in early triple-negative breast cancer independent of pathological complete response.

BACKGROUND: Addition of immune checkpoint inhibitors to neoadjuvant chemotherapy (NACT) is a promising strategy in early breast cancer, but the optimal duration of therapy is currently unknown. In the GeparNuevo (NCT02685059) trial, addition of durvalumab to NACT as previously reported led to a moderate increase in pathological complete response (pCR) rate by an absolute 9% (P = 0.287). PATIENTS AND METHODS: Patients with cT1b-cT4a-d triple-negative breast cancer (TNBC) received durvalumab 1.5 g or placebo every 4 weeks added to nab-paclitaxel 125 mg/m2 weekly for 12 weeks, followed by durvalumab/placebo every 4 weeks plus epirubicin/cyclophosphamide every 2 weeks followed by surgery. Durvalumab was not continued after surgery. The primary objective was pCR. Secondary endpoints included invasive disease-free survival (iDFS), distant disease-free survival (DDFS) and overall survival (OS). RESULTS: A total of 174 patients were randomised between June 2016 and October 2017. After a median follow-up of 43.7 months, 34 events had occurred. Despite a non-significant increase in the pCR rate, significant differences were observed for 3-year iDFS, DDFS and OS: iDFS was 85.6% with durvalumab versus 77.2% with placebo [hazard ratio (HR) 0.48, 95% confidence interval (CI) 0.24-0.97, stratified log-rank P = 0.036]; DDFS 91.7% versus 78.4% (HR 0.31, 95% CI 0.13-0.74, P = 0.005); OS 95.2% versus 83.5% (HR 0.24, 95% CI 0.08-0.72, P = 0.006). pCR patients had 3-year iDFS of 95.5% with durvalumab and 86.1% without (HR 0.22, 95% CI 0.05-1.06). In the non-pCR cohort 3-year iDFS was 76.3% versus 69.7% (HR 0.67, 95% CI 0.29-1.54). Multivariable analysis confirmed a durvalumab effect independent of the pCR effect. No new safety signals occurred. CONCLUSIONS: Durvalumab added to NACT in TNBC significantly improved survival despite a modest pCR increase and no adjuvant component of durvalumab. Additional studies are needed to clarify the optimal duration and sequence of checkpoint inhibitors in the treatment of early TNBC.

Outcome of breast cancer patients with low hormone receptor positivity: analysis of a 15-year population-based cohort.

BACKGROUND: Guideline recommendations for the treatment of breast cancer with low hormone receptor (HR) expression (1%-9%) are ambiguous and several studies showed more similarities with HR-negative tumors than with HR strongly positive tumors (≥10%). We used a population-based 15-year cohort to compare patient characteristics and outcome of HR low positive tumors with HR-negative and HR strongly positive tumors, respectively. PATIENTS AND METHODS: A total of 38  560 women diagnosed with early invasive breast cancer between 2004 and 2018 within the scope of the Munich Cancer Registry with 4.9 million inhabitants were included. Descriptive analyses of prognostic factors, treatment, and outcome analyses using the Kaplan-Meier method; cumulative incidence in consideration of competing risks; and multivariate analyses (Cox regression and Fine-Gray model) were conducted. Endpoints were time to local recurrence (TTLR), time to lymph node recurrence (TTLNR), time to metastasis (TTM), overall survival (OS), and relative survival (RS). RESULTS: A total of 861 patients (2%) had HR low positive, 4862 (13%) HR-negative, and 32  837 (85%) HR strongly positive tumors. Within the HER2-negative cohort (n = 33  366), survival of HR low positive tumors was significantly worse than that of HR strongly positive tumors [OS hazard ratio 0.66 (95% confidence interval 0.55-0.78)], whereas between HR low positive and HR-negative tumors no significant survival difference could be detected [OS hazard ratio 0.93 (95% confidence interval 0.78-1.11)]. TTLR, TTLNR, and TTM showed similar results. By contrast, within the HER2-positive cohort (n = 5194), no statistically significant differences between the three HR groups could be detected in multivariate analyses. CONCLUSION: Current definitions for HR positivity and its clinical relevance should be reconsidered. Patients with HR low positive/HER2-negative tumors could be regarded and treated similar to patients with triple-negative tumors.

Congruence and trajectories of device-measured and self-reported physical activity during therapy for early breast cancer.

PURPOSE: This study examines congruence between self-reported and device-measured physical activity data in women with early breast cancer and compares trajectories under different treatments. METHODS: Women with non-metastatic breast cancer were recruited before primary therapy. In four weeks distributed over six months after treatment start, patients reported time spent on work, transport, chores and sports via diary and wore Garmin® vivofit 3 accelerometers to assess steps taken. Associations between these measures and agreement regarding guideline adherence were tested with Spearman's Correlation Coefficient and Weighted Kappa statistic. Effects of time and treatment were evaluated using mixed analyses of variance. RESULTS: Ninety-nine participants (median age = 50) were treated with adjuvant (N = 23), neoadjuvant (N = 21) or without chemotherapy (N = 55). Coherence between self-report and device data was strong (r = 0.566). Agreement about reaching recommendations was only "fair" (kappa coefficient = 0.321 and 0.249, resp.). Neither treatment or week nor their interaction had effects on step counts (all p > 0.05). Self-reported activity time was lower for patients with chemotherapy than for those without (adjuvant: ∆ = 69min, p = 0.006, neoadjuvant: ∆ = 45min, p = 0.038) and lower in week 18 than in week 3 (∆ = 43min, p = 0.010). CONCLUSION: Results show that consumer-grade activity monitors and self-reports correlate but show different perspectives on physical activity in breast cancer patients. In general, patients perceive some decline regardless of primary treatment regimen. Those affected should be offered assistance to gain the benefits of activity. Accelerometers may help professionals to identify these individuals and patients to verify appraisal of their activity levels.

Sentinel lymph node mapping with indocyanine green compared to blue dye tracer in gynecologic malignancies-A single center experience of 218 patients.

BACKGROUND AND OBJECTIVES: To compare the detection rates of sentinel lymph nodes after converting the tracer technique from blue dye to indocyanine green (ICG). METHODS: Patients with uterine or cervical cancer were enrolled for sentinel lymph node (SLN) dissection. A total of 109 consecutive patients were analyzed and compared to a historical cohort of 109 consecutive patients with the sentinel blue dye technique. SLNs were analyzed by ultrastaging. RESULTS: The bilateral mapping rate of sentinel nodes was significantly higher with the ICG (78%; n = 85) compared to the blue dye tracer (61%; n = 67; p = .006). Neither the mean number of SLN nor the rate of low volume metastases showed significant differences between both cohorts. In the subgroup of endometrial cancer patients, the number of systematic lymph node dissection (LND) was significantly lower in the ICG cohort compared to the blue dye cohort (9% vs. 28%, p = .001). CONCLUSIONS: ICG improved the detection rate of pelvic SLN compared to blue dye and may be considered as the superior technique. In clinical practice, the rate of systematic LND further decreased after incorporating SLN mapping with ICG. Reliable safety data are still pending.

Distributed Global Debris Thickness Estimates Reveal Debris Significantly Impacts Glacier Mass Balance.

Supraglacial debris affects glacier mass balance as a thin layer enhances surface melting, while a thick layer reduces it. While many glaciers are debris-covered, global glacier models do not account for debris because its thickness is unknown. We provide the first globally distributed debris thickness estimates using a novel approach combining sub-debris melt and surface temperature inversion methods. Results are evaluated against observations from 22 glaciers. We find the median global debris thickness is ∼0.15 ± 0.06 m. In all regions, the net effect of accounting for debris is a reduction in sub-debris melt, on average, by 37%, which can impact regional mass balance by up to 0.40 m water equivalent (w.e.) yr-1. We also find recent observations of similar thinning rates over debris-covered and clean ice glacier tongues is primarily due to differences in ice dynamics. Our results demonstrate the importance of accounting for debris in glacier modeling efforts.

Concordance of the molecular subtype classification between core needle biopsy and surgical specimen in primary breast cancer.

BACKGROUND: Molecular profiling of breast cancer (BC) classifies several intrinsic subtypes based on different patterns of gene expression. Multigene assays estimate the risk of recurrence and help to select high-risk patients for adjuvant chemotherapy. However, these tests are associated with significant costs. Immunohistochemistry (IHC) offers a surrogate classification for molecular subtypes by determining estrogen (ER) and progesterone receptors (PR), human epidermal growth factor (Her2neu), as well as the proliferation marker Ki67. Core needle biopsy (CNB) is well established in BC diagnosis and allows a pre-operative assessment of biomarkers. The aim of this study was to analyze the concordance of these markers between CNB and surgical specimens to assess whether re-testing of the surgical specimen is mandatory. MATERIALS AND METHODS: Within a 3-year period, patients with primary BC and paired samples of CNB and surgical specimens were analyzed retrospectively. Concordance rates of ER, PR, Her2neu, Ki67, and the surrogate classification for molecular subtypes were calculated using the Landis and Koch agreement grades. RESULTS: Out of 2254 patients with primary breast cancer, 1307 paired specimens without pre-operative treatment were available for analysis Concordance rates for ER, PR, Her2neu, and Ki67 status showed substantial-to-almost perfect agreement grades (κ = 0.91, 0.75, 0.89, and 0.61, respectively). Though substantial concordance was also found for the subtype classification (κ = 0.70), the molecular subtype changed in 18.5% of patients based on the testing of the surgical specimen, mainly from luminal A-like to luminal B-like. CONCLUSIONS: Though the concordance rates for single markers were convincing, a significant proportion of the molecular subtypes differed between CNB and the surgical specimen. Re-testing of PR and Ki67 is mandatory to ensure optimal treatment decisions. Further research is necessary to define safe, efficient, and cost-effective predictive models in adjuvant breast cancer therapy.

[Improved image quality of the cervical spine neck CT using an arm traction device]. / Verbesserte Bildqualität der Halswirbelsäulen-CT mittels Armzugvorrichtung.

BACKGROUND: The assessment of the cervico-thoracic junction in the neck CT is frequently hampered by streak artifacts from the shoulder girdles. PURPOSE: To evaluate the effects of an optimized patient positioning through the use of an arm traction device. MATERIALS AND METHODS: 25 patients (age [mean ± standard deviation]: 58.9 ± 11.6 years; sex [m:f]: 15:10) underwent a neck CT using an arm traction device together. Further 25 patients underwent this in standard positioning (59.8 ± 15.2 years; 16:9). An experienced neuroradiologist determined the last free accessible vertebra on the CT scout view and assessed the image quality of the intervertebral disc space of the lower neck on a three-point grading scale. The procedure was evaluated by the medical-technical radiology assistants performing it. RESULTS: The last free accessible vertebra on CT scout was statistically significant one vertebra lower using an arm traction device, yielding on average the sixth cervical vertebra (p = 0.010). Subjective image quality increased in all evaluated intervertebral disc spaces (median and absolute frequencies [good/middle/bad]: 1.0 [53/21/8] vs. 2.0 [41/30/24]), resulting in a statistically significant effect between the cervical vertebra 6/7 (p = 0.0041). The traction device approach was rated to be suitable for daily routine in the categories of patient's cooperation (good), comprehensibility for the patient (84%) and management for the assistants (good). CONCLUSION: Using an arm traction device on neck CT both the accessibility of vertebra on CT scout increased and image quality of the cervico-thoracic junction improved. The simply applicable device could be favourable for cooperative patients with lower neck pathology.

Innervation and vascular supply of the first dorsal interosseous muscle and palmar interosseous muscle of the index: An anatomic descriptive study.

INTRODUCTION: The first dorsal interosseous muscle (FDI) and palmar interosseous muscle of the index (P2I) are essential for the strength and mobility of the index finger. This study aims to describe the course of the deep branch of the ulnar nerve (DBUN) and the blood supply to these muscles. MATERIAL AND METHODS: An anatomical cadaver study was carried out with 14 upper limbs from fresh, non-embalmed cadavers. All limbs were filled with an equal amount, based on weight, of colored silicone and diluent that was combined and catalyzed with 5% curing agent. The location of the DBUN's termination was specified relative the carpometacarpal joint. Every artery supplying either muscle was identified and documented. RESULTS: The DBUN had a slightly convex path, distal to the hook of the hamate and penetrated the FDI muscle at an average 41% of the second metacarpal length. An average of 1.3 branches to the P2I and 2.6 branches to the FDI were found. Four artery pedicles coming from the deep palmar arch supply the FDI with an average of one consistent and exclusive pedicle to the FDI and three pedicles heading to the P2I. According to the classification of Mathes and Nahai, the FDI has a type 2 blood supply and the P2I has a type 3 blood supply. CONCLUSION: In-depth knowledge of the vascular network supplying the FDI and P2I muscles and the course of the DBUN is essential when the DBUN is damaged or when dissecting these muscles for index pollicization.

The ophthalmic artery: a new variant involving two branches from the supracavernous internal carotid artery.

PURPOSE: We report an extremely rare, double ophthalmic artery configuration. METHODS: We present 2D- and 3D-angiographic features of an anomalous origin of the ophthalmic artery. RESULTS: The double ophthalmic artery was the result of the persistence of the primitive dorsal ophthalmic artery combined with the presence of a second orbital artery originating from the supracavernous internal carotid artery, passing through the superior orbital fissure and into the orbit to furnish the muscular, lacrimal and ethmoidal arteries and the medial long posterior ciliary artery. CONCLUSIONS: A heretofore undocumented instance of ophthalmic artery duplication is presented. Knowledge of such variations is important for the planning of endovascular treatments and the comprehension of unusual angiographic images. Such fine arterial variants may very well be frequent, but difficult to demonstrate on simple 2D angiographies. Multiplanar reconstructions of 3D angiography data make it possible to diagnose rare, but embryologically predictable arterial variants.

Quantifying efficacy of investigation during a simulated psychiatric interview.

INTRODUCTION: Simulation is a very promising educational tool. It provides medical students with clinical experience without jeopardizing patients' health. This tool can be implemented in psychiatry training in order to develop interview and specific assessment skills which is why the Université de Lorraine relies increasingly on simulation in teaching psychiatry to its residents. However, there are few objective indicators in that field that make it possible to assess learners. This study aims to assess the relevance of a quantitative measure for objectivising the investigation efficiency by psychiatry residents of a suicidal risk during a simulated psychiatric interview. METHODS: A simulation exercise was offered to 20 psychiatric trainees from the Université de Lorraine. Their mission was to identify relevant information for assessing and guiding a standardized patient with suicidal risk during a psychiatric interview. The key judgemental criterion was the I2/Q ratio which corresponds to the squared number of relevant items collected by the interviewer divided by the number of questions. When dealing with emergency cases it is indeed important to collect as many key items in as little time as possible. This score was assessed by two examiners based on the analysis of filmed interviews. RESULTS: The mean I2/Q ratio was 1.13 (SEM±0.2) and ranged between 0.25 and 2.86. Statistical analysis showed a positive correlation between I2/Q ratio and students' clinical experience (R=0.46, P=0.04). The interclass correlation coefficient (ICC) of the I2/Q ratio between the two examiners was 0.94. CONCLUSION: I2/Q ratio may provide a consistent quantitative measure of a student's efficiency in assessing suicidal risk. Further research is now needed to evaluate its consistency in other clinical cases.

Outcome of fetuses with lower urinary tract obstruction and normal amniotic fluid volume in second trimester of pregnancy.

OBJECTIVE: Congenital lower urinary tract obstruction (LUTO) is a rare condition with high perinatal mortality and morbidity when associated with severe oligohydramnios or anhydramnios in the second trimester of pregnancy. Severe pulmonary hypoplasia and end-stage renal disease are the underlying causes of poor neonatal outcome in these cases. However, little is known about the subset of fetal LUTO that is associated with a normal volume of amniotic fluid at midgestation. The objective of the current study was to describe the natural history, underlying causes, survival and postnatal renal function outcomes in pregnancies with fetal LUTO and normal amniotic fluid volume during the second trimester of pregnancy. METHODS: This was a retrospective study of all pregnancies with fetal LUTO and normal amniotic fluid volume in the second trimester that received prenatal and postnatal care at our quaternary care institution between 2013 and 2017. Data on demographic characteristics, fetal interventions, perinatal survival, need for neonatal respiratory support, postnatal renal function and need for dialysis at the age of 1 and 24 months were analyzed. RESULTS: Of the 18 fetuses that met the study criteria, 17 (94.4%) survived the perinatal period. Eleven (61.1%) pregnancies developed oligohydramnios in the third trimester, six of which were eligible for and underwent fetal intervention with vesicoamniotic shunt placement, which was performed successfully in all six cases. Two (11.1%) neonates required respiratory support owing to pulmonary hypoplasia. At the age of 2 years, 14 children had follow-up information available, two (14.3%) of whom had normal renal function, eight (57.1%) had developed some degree of chronic kidney disease (Stage 1-4) and four (28.6%) had developed end-stage renal disease (ESRD), including two who had already manifested ESRD in the neonatal period. CONCLUSIONS: Most fetuses diagnosed prenatally with LUTO that is associated with a normal volume of amniotic fluid at midgestation will have a favorable outcome in terms of perinatal survival and few will need long-term respiratory support. However, these children are still at increased risk for chronic renal disease, ESRD and need for renal replacement therapy. Larger multicenter studies are needed to characterize the prenatal factors associated with postnatal renal function, and to investigate the role of fetal intervention in the group of fetuses that present with late-onset oligohydramnios and evidence of preserved fetal renal function. Copyright © 2019 ISUOG. Published by John Wiley & Sons Ltd.

From ligand exchange to reaction intermediates: what does really happen during the synthesis of emissive complexes?

In situ monitoring of the formation of emissive complexes is essential to enable the development of rational synthesis protocols, to provide accurate control over the generation of structure-related properties (such as luminescence) and to facilitate the development of new compounds. In situ luminescence analysis of coordination sensors (ILACS) utilizes the sensitivity of the spectroscopic properties of lanthanide ions to their coordination environment to detect structural changes during crystallization processes. Here, ILACS was utilized to monitor the formation of [Eu(bipy)2(NO3)3] (bipy = 2,2'-bipyridine) during co-precipitation synthesis. Validity of the ILACS results was ensured by concomitant utilization of in situ monitoring of other reaction parameters, including in situ measurements of pH value, ionic conductivity, and infrared spectra, as well as ex situ and synchrotron-based in situ X-ray diffraction analyses. Gradual desolvation of the Eu3+ ions and attachment of ligands were detected by an exponential increase of the intensity of the 5D0 → 7FJ (J = 0-4) transitions in the emission spectrum. Additionally, the in situ emission spectra show a decrease in the crystallization rate and an increase in the induction time in response to a reduction in the concentration of the starting solutions from 12 mM until crystallization ceased at starting reactant concentrations <6 mM. An increase to a three-fold higher concentration leads to the formation of a reaction intermediate, and its stability was determined to be highly concentration-dependent. The in situ luminescence measurements also demonstrated the existence of a ligand exchange process within the [Eu(bipy)2(NO3)3] complex upon addition of a phen (phen = 1,10'-phenanthroline) solution and the generation of a new phen-containing emissive complex. In attempting to solve the structure of this new phen-containing complex, a different, but nevertheless previously unsynthesized complex, [Eu(phen)2(NO3)3]bipy, was obtained, which shows characteristic Eu3+ luminescence in the red spectral range.

[Human hantavirus infections]. / Die humane Hantavirus-Infektion: Eine Literaturübersicht.

Hantaviruses belong to the Bunyaviridae family. A large number of different subtypes are known worldwide that show a host-specific geographical distribution. Humans may become infected through contact with rodent urine, saliva or feces. In humans, hantavirus infections are an important and worldwide emerging zoonotic disease that may result in a variety of potentially life-threatening diseases, e. g. hemorrhagic fever with renal syndrome (HFRS) and hantavirus cardiopulmonary syndrome (HCPS). There are various aspects of major occupational importance, particularly for agriculturists, veterinarians and forestry workers. This article reviews the current knowledge about epidemiology, pathology, diagnostics, therapy and prevention of human hantavirus infections worldwide.

De-escalation strategies in HER2-positive early breast cancer (EBC): final analysis of the WSG-ADAPT HER2+/HR- phase II trial: efficacy, safety, and predictive markers for 12 weeks of neoadjuvant dual blockade with trastuzumab and pertuzumab ± weekly paclitaxel.

BACKGROUND: Response rates in HER2-overexpressing EBC treated with neoadjuvant chemotherapy and trastuzumab (T) have been improved by addition of pertuzumab (P). The prospective, phase II, neoadjuvant WSG-ADAPT HER2+/HR- trial assessed whether patients with strong early response to dual blockade alone might achieve pathological complete response (pCR) comparable to that of patients receiving dual blockade and chemotherapy. PATIENTS AND METHODS: Female patients with HER2+/HR- EBC (M0) were randomized (5:2) to 12 weeks of T + P ± weekly paclitaxel (pac) at 80 mg/m2. Early response was defined as proliferation decrease ≥30% of Ki-67 (versus baseline) or low cellularity (<500 invasive tumor cells) in the 3-week biopsy. The trial was designed to test non-inferiority for pCR in early responding patients of the T + P arm versus all chemotherapy-treated patients. RESULTS: From February 2014 to December 2015, 160 patients were screened, 92 were randomized to T + P and 42 to T + P+pac. Baseline characteristics were well balanced (median age 54 versus 51.5 years, cT2 51.1 versus 52.4%, cN0 54.3 versus 61.9%); 91.3% of patients completed T + P per protocol and 92.9% T + P+pac. The pCR rate in the T + P+pac arm was 90.5%, compared with 36.3% in the T + P arm as a whole. In the T + P arm, 24/92 were classified as non-responders, and their pCR rate was only 8.3% compared with 44.7% in responders (38/92) and 42.9% in patients with unclassified early response (30/92). No new safety signals were observed in the study population. CONCLUSION: Addition of taxane monotherapy to dual HER2 blockade in a 12-week neoadjuvant setting substantially increases pCR rates in HER2+/HR- EBC compared with dual blockade alone, even within early responders to dual blockade. Early non-response under dual blockade strongly predicts failure to achieve pCR.

Long-term health outcomes in patients with Prader-Willi Syndrome: a nationwide cohort study in Denmark.

BACKGROUND: Prader-Willi syndrome (PWS) is a rare congenital disease that affects growth, sexual development, cognitive function and behavior. Individuals exhibit food preoccupation and hyperphagia, which may lead to obesity with premature morbidity and mortality. The aim of this work was to evaluate the risk of venous thromboembolisms (VTEs), myocardial infarction, pulmonary hypertension, sleep apnea, depression, anxiety and all-cause mortality among persons with PWS as compared with an age- and sex-matched general-population cohort. METHODS: All persons diagnosed with PWS (n=155) were identified in the Danish Health Registries; an age- and sex-matched comparison group was selected from the general population of Denmark (n=15 500); diseases of interest were identified through the health registry and cause of death register. Follow-up began on date of birth or first medical record availability through to first occurrence of an outcome of interest; follow-up ceased at emigration from Denmark or end of study. Incidence rates (IRs) were calculated and Cox's proportional hazards models were used to understand the relative risk (RR) of disease. RESULTS: The IRs for VTE among patients with PWS was 144 (60-347) per 100 000 person-years. Risks for VTE events and all-cause mortality were 9.4 times (95% confidence interval (CI): 3.7-23.5) and 11.0 times (95% CI: 5.7-21.1) higher, respectively, for patients with PWS versus the general population. Increased risks were also found individually for deep venous thromboses (DVTs) (RR: 9.1; 95% CI: 3.2-25.2), pulmonary embolisms (RR: 11.0; 95% CI: 1.4-86.9), myocardial infarction (RR: 7.2; 95% CI: 1.7-30.2) and anxiety (RR: 2.8; 95% CI: 1.0-7.5). No cases of pulmonary hypertension, sleep apnea or depressive disorders were identified within this PWS cohort. CONCLUSIONS: Multiple cardiovascular and behavioral illnesses are more likely to occur among patients with PWS than within the general population. These increased risks may provide an impetus for enhanced disease prevention, screening, diagnosis and treatment.

Heterogeneity and concordance in locus-specific differentiation and introgression between species of towhees.

The maintenance or breakdown of reproductive isolation is an observable outcome of secondary contact between species. In cases where hybrids beyond the F1 are formed, the representation of each species' ancestry can vary dramatically among genomic regions. This genomic heterogeneity in ancestry and introgression can offer insight into evolutionary processes, particularly if introgression is compared in multiple hybrid zones. Similarly, considerable heterogeneity exists across the genome in the extent to which populations and species have diverged, reflecting the combined effects of different evolutionary processes on genetic variation. We studied hybridization across two hybrid zones of two phenotypically well-differentiated bird species in Mexico (Pipilo maculatus and P. ocai), to investigate genomic heterogeneity in differentiation and introgression. Using genotyping-by-sequencing (GBS) and hierarchical Bayesian models, we genotyped 460 birds at over 41 000 single nucleotide polymorphism (SNP) loci. We identified loci exhibiting extreme introgression relative to the genome-wide expectation using a Bayesian genomic cline model. We also estimated locus-specific FST and identified loci with exceptionally high genetic divergence between the parental species. We found some concordance of locus-specific introgression in the two independent hybrid zones (6-20% of extreme loci shared across zones), reflecting areas of the genome that experience similar gene flow when the species interact. Additionally, heterogeneity in introgression and divergence across the genome revealed another subset of loci under the influence of locally specific factors. These results are consistent with a history in which reproductive isolation has been influenced by a common set of loci in both hybrid zones, but where local environmental and stochastic factors also lead to genomic differentiation.