Pathfinder experiments with atom interferometry in the Cold Atom Lab onboard the International Space Station.

Deployment of ultracold atom interferometers (AI) into space will capitalize on quantum advantages and the extended freefall of persistent microgravity to provide high-precision measurement capabilities for gravitational, Earth, and planetary sciences, and to enable searches for subtle forces signifying physics beyond General Relativity and the Standard Model. NASA's Cold Atom Lab (CAL) operates onboard the International Space Station as a multi-user facility for fundamental studies of ultracold atoms and to mature space-based quantum technologies. We report on pathfinding experiments utilizing ultracold 87Rb atoms in the CAL AI. A three-pulse Mach-Zehnder interferometer was studied to understand the influence of ISS vibrations. Additionally, Ramsey shear-wave interferometry was used to manifest interference patterns in a single run that were observable for over 150 ms free-expansion time. Finally, the CAL AI was used to remotely measure the Bragg laser photon recoil as a demonstration of the first quantum sensor using matter-wave interferometry in space.

Clinical management and innovation in fracture non-union.

INTRODUCTION: With the introduction and continuous improvement in operative fracture fixation, even the most severe bone fractures can be treated with a high rate of successful healing. However, healing complications can occur and when healing fails over prolonged time, the outcome is termed a fracture non-union. Non-union is generally believed to develop due to inadequate fixation, underlying host-related factors, or infection. Despite the advancements in fracture fixation and infection management, there is still a clear need for earlier diagnosis, improved prediction of healing outcomes and innovation in the treatment of non-union. AREAS COVERED: This review provides a detailed description of non-union from a clinical perspective, including the state of the art in diagnosis, treatment, and currently available biomaterials and orthobiologics.Subsequently, recent translational development from the biological, mechanical, and infection research fields are presented, including the latest in smart implants, osteoinductive materials, and in silico modeling. EXPERT OPINION: The first challenge for future innovations is to refine and to identify new clinical factors for the proper definition, diagnosis, and treatment of non-union. However, integration of in vitro, in vivo, and in silico research will enable a comprehensive understanding of non-union causes and correlations, leading to the development of more effective treatments.

Usability of a visual feedback system to assess and improve movement disorders related to neck pain: Perceptions of physical therapists and patients.

A prototype visual feedback system has been developed to assess and improve movement disorders related to neck pain. The aim of this study was to assess the usability of the prototype in a rehabilitation setting. Twelve physical therapists integrated the device into their regular therapy programs for 24 neck pain patients with movement disorders. Each patient performed three individual therapy sessions with the device under physical therapist supervision. Usability was assessed by the physical therapists and patients using therapy diaries, the System Usability Scale, and focus group or personal interviews. Based on an overall usability rating of marginally acceptable, the visual feedback system was generally found to be a device with the potential to assess and train neck pain patients but needs improvement. To become a useful adjunct to regular physical therapy, improvements in the hardware and software, and further system developments are required.

Multicenter study of the safety and effectiveness of intracranial aneurysm treatment with the p64MW-HPC flow modulation device.

BACKGROUND AND PURPOSE: The new p64 flow diverter with hydrophilic polymer coating (HPC) was designed to reduce thrombogenicity. To date, it is unclear how antithrombogenic surface modifications affect neoendothelialization and thrombus formation in patients with unruptured intracranial aneurysms. The purpose of this study was to evaluate the safety and effectiveness of the p64MW-HPC in the treatment of unruptured aneurysms of small to giant size and of both the anterior and posterior circulation. MATERIALS AND METHODS: Between March 2020 and October 2022 all patients with unruptured intracranial aneurysms treated with the p64MW-HPC were included at five neurovascular centers. Demographic data, aneurysm characteristics, antiplatelet therapy, procedural complications, and clinical and angiographic outcomes were recorded. RESULTS: A total of 100 patients with 100 unruptured intracranial aneurysms met the inclusion criteria. Eighty-three aneurysms were classified as saccular, 12 aneurysms were fusiform, 4 aneurysms dissecting, and 1 aneurysm was blister-like. Dual antiplatelet therapy with Clopidogrel and Aspirin was given in 68 cases, and with Ticagrelor and Aspirin in 24 cases. Technical issues with deployment were encountered in 14 cases (torsion (n = 3), foreshortening (n = 8), and incomplete opening (n = 3)). Ischemic stroke occurred in a total of seven cases. In one patient a wire perforation and subsequent severe ICH occurred. Complete aneurysm occlusion at angiographic follow-up (mean time = 7 months) was seen in 73% and adequate occlusion in 93%. CONCLUSION: This study is the largest multicenter study to date documenting the safety and effectiveness of the new antithrombogenic p64MW-HPC in the treatment of unruptured intracranial aneurysms of the anterior and posterior circulation.

Reproducibility of pulmonary function tests in patients with systemic sclerosis.

Systemic sclerosis (SSc) is a rare autoimmune disease in which interstitial lung disease (ILD) is the leading cause of morbidity and mortality. Clinical management of the lung disease is mainly based on pulmonary function testing (PFT) and their changes over time. Little is known about the reproducibility of PFT testing in SSc patients. The aim of this study was to assess the test-retest reliability and reproducibility of PFTs in SSc patients with or without ILD over 30 days in order determine the potential physiologic variation over the time. We performed prospective observational study of SSc patients. The FVC, FEV1/FVC ratio, DLCO and KCO parameters were assessed in this population at four different timepoints; T0 (time 0) and H3 (T0 + 3 h) defined test-retest reliability, D15 (T0 + 15 days) and D30 (T0 + 30 days) for reproducibility. A mixed linear model was used to test the effect of time (and therefore reproducibility) on patients and we looked for an interaction. We included 25 SSc patients divided in two groups, 14 with ILD and 11 non-ILD. Interactions between time and group were not significant and were not reported. Time and group did not significantly influence the different measures of the PFT: FVC [p values time and group effect respectively (0.33; 0.34)], FEV1/FVC ratio (0.093; 0.056) and DLCO (0.99; 0.13) in the ILD and non ILD group (Table S2). The analyse with interactions between time and group were not significant and are not reported. We also used a Bland Altman test to assess reproducibility for FVC (L) and DLCO (mMKpa/min/L), Figs. 1 and 2 respectively. The measurements were therefore reproducible over time and in each group. PFT parameters are reproducible over time in a clinically stable population of SSc (no significant effect of the time T0, H3, D15 and D30) and there is no significant distinction between patients with ILD and no ILD. These respiratory functional data can further underline their use in clinical practice.

Surgical Treatment of Patients with Sacroiliac Joint Syndrome: Comparative Study of Two Implants. / Operative Behandlung von Patienten mit Iliosakralgelenksyndrom: Vergleichsstudie zweier Implantate.

The treatment of patients with ISJ dysfunction is difficult due to the multifactorial causes of pain and various problems in clarification. Treatment includes physical therapy, corticosteroids, prolotherapy, radiofrequency denervation and sacroiliac joint fusion. A new option for the surgical treatment of ISG dysfunction is the Torpedo implant system. For a safe fusion, only 2 implants are needed, which are available in lengths of 30-50 mm. The new implant system has been tested in pilot studies for efficacy and biocompatibility with good results. For further documentation for the Torpedo implant system, a comparative study against the iFuse system was carried out.Two different implants were used: Group 1: Deltacor Torpedo, Group 2: iFuse implants (Si-Bone). The data generated during admission and subsequent check-ups (VAS, ODI, opioid use) were entered into an evaluation file set up for this purpose. Follow-up appointments were set at 1 month, 3, 6 and 12 months postoperatively.The data of 65 patients were evaluated comparatively. In all comparisons, only very small effect sizes were found with regard to the differences in the decrease in pain intensities, so that equivalent effectiveness of the two methods could initially be postulated from a clinical point of view. Most patients in both groups reported taking opioids to treat pain before surgery. According to the decrease in pain intensity, opioid treatment could be discontinued in some patients after the operation. After 12 months, the number of patients treated with opioids decreases to 23% in group 1 and to 17% in group 2. The success of the fusions with the two methods can also be proven by image documentation, from which the position of the implants can also be clearly recognised. In no case was there any loosening.Overall, the evaluation of this study allows the conclusion that both implant systems can be successfully used for the treatment of patients with ISJ syndrome. The present results should be confirmed in further comparative studies with the proposed evaluation methods.

Quantum gas mixtures and dual-species atom interferometry in space.

The capability to reach ultracold atomic temperatures in compact instruments has recently been extended into space1,2. Ultracold temperatures amplify quantum effects, whereas free fall allows further cooling and longer interactions time with gravity-the final force without a quantum description. On Earth, these devices have produced macroscopic quantum phenomena such as Bose-Einstein condensates (BECs), superfluidity, and strongly interacting quantum gases3. Terrestrial quantum sensors interfering the superposition of two ultracold atomic isotopes have tested the universality of free fall (UFF), a core tenet of Einstein's classical gravitational theory, at the 10-12 level4. In space, cooling the elements needed to explore the rich physics of strong interactions or perform quantum tests of the UFF has remained elusive. Here, using upgraded hardware of the multiuser Cold Atom Lab (CAL) instrument aboard the International Space Station (ISS), we report, to our knowledge, the first simultaneous production of a dual-species BEC in space (formed from 87Rb and 41K), observation of interspecies interactions, as well as the production of 39K ultracold gases. Operating a single laser at a 'magic wavelength' at which Rabi rates of simultaneously applied Bragg pulses are equal, we have further achieved the first spaceborne demonstration of simultaneous atom interferometry with two atomic species (87Rb and 41K). These results are an important step towards quantum tests of UFF in space and will allow scientists to investigate aspects of few-body physics, quantum chemistry and fundamental physics in new regimes without the perturbing asymmetry of gravity.

Compliance-Adjusted Estimates of Aspirin Effects Among Older Persons in the ASPREE Randomized Trial.

The Aspirin in Reducing Events in the Elderly (ASPREE) Trial recruited 19,114 participants across Australia and the United States during 2010-2014. Participants were randomized to receive either 100 mg of aspirin daily or matching placebo, with disability-free survival as the primary outcome. During a median 4.7 years of follow-up, 37% of participants in the aspirin group permanently ceased taking their study medication and 10% commenced open-label aspirin use. In the placebo group, 35% and 11% ceased using study medication and commenced open-label aspirin use, respectively. In order to estimate compliance-adjusted effects of aspirin, we applied rank-preserving structural failure time models. The results for disability-free survival and most secondary endpoints were similar in intention-to-treat and compliance-adjusted analyses. For major hemorrhage, cancer mortality, and all-cause mortality, compliance-adjusted effects of aspirin indicated greater risks than were seen in intention-to-treat analyses. These findings were robust in a range of sensitivity analyses. In accordance with the original trial analyses, compliance-adjusted results showed an absence of benefit with aspirin for primary prevention in older people, along with an elevated risk of clinically significant bleeding.

The relationship between long-term blood pressure variability and cortical thickness in older adults.

High blood pressure variability (BPV) is a risk factor for cognitive decline and dementia, but its association with cortical thickness is not well understood. Here we use a topographical approach, to assess links between long-term BPV and cortical thickness in 478 (54% men at baseline) community dwelling older adults (70-88 years) from the ASPirin in Reducing Events in the Elderly NEURO sub-study. BPV was measured as average real variability, based on annual visits across three years. Higher diastolic BPV was significantly associated with reduced cortical thickness in multiple areas, including temporal (banks of the superior temporal sulcus), parietal (supramarginal gyrus, post-central gyrus), and posterior frontal areas (pre-central gyrus, caudal middle frontal gyrus), while controlling for mean BP. Higher diastolic BPV was associated with faster progression of cortical thinning across the three years. Diastolic BPV is an important predictor of cortical thickness, and trajectory of cortical thickness, independent of mean blood pressure. This finding suggests an important biological link in the relationship between BPV and cognitive decline in older age.

Microsurgical clipping as a retreatment strategy for previously ruptured aneurysms treated with the Woven EndoBridge (WEB) device: a mono-institutional case series.

BACKGROUND: Since its approval by the US Food and Drug Administration (FDA) in 2018, the flow disruptor Woven EndoBridge (WEB) device has become increasingly popular for the endovascular treatment of unruptured and ruptured cerebral aneurysms. However, the occlusion rates seem rather low and the retreatment rates rather high compared to other treatment methods. For initially ruptured aneurysms, a retreatment rate of 13 % has been reported. A variety of retreatment strategies has been proposed; however, there is a paucity of data concerning microsurgical clipping of WEB-pretreated aneurysms, especially previously ruptured ones. Thus, we present a single-center series of five ruptured aneurysms treated with the WEB device and retreated with microsurgical clipping. METHODS: A retrospective study including all patients presenting with a ruptured aneurysm undergoing WEB treatment at our institution between 2019 and 2021 was performed. Subsequently, all patients with an aneurysm remnant or recurrence of the target aneurysm retreated with microsurgical clipping were identified. RESULTS: Overall, five patients with a ruptured aneurysm treated with WEB and retreated with microsurgical clipping were included. Besides one basilar apex aneurysm, all aneurysms were located at the anterior communicating artery (AComA) complex. All aneurysms were wide-necked with a mean dome-to-neck ratio of 1.5. Clipping was feasible and safe in all aneurysms, and complete occlusion was achieved in 4 of 5 aneurysms. CONCLUSIONS: Microsurgical clipping for initially ruptured WEB-treated aneurysms is a feasible, safe, and effective treatment method in well-selected patients.

Incidence of biopsy-proven giant cell arteritis (GCA) in South Australia 2014-2020.

Objective: To determine the incidence of biopsy proven giant cell arteritis (GCA) in South Australia. Methods: Patients with biopsy-proven GCA were identified from pathology reports of temporal artery biopsies at state-based pathology laboratories, from 1 January 2014 to 31 December 2020. Incidence rates for biopsy-proven GCA were calculated using Australian Bureau of Statistics data for South Australian population sizes by age, sex, and calendar year. Seasonality was analyzed by cosinor analysis. Results: There were 181 cases of biopsy-proven GCA. The median age at diagnosis of GCA was 76 years (IQR 70, 81), 64% were female. The estimated population incidence for people over 50 was 5.4 (95% CI 4.7, 6.1) per 100,000-person years. The female: male incidence ratio was 1.6 (95% CI 1.2, 2.2). There was no ordinal trend in GCA incidence rates by calendar year (p = 0.29). The incidence was, on average, highest in winter, but not significantly (p = 0.35). A cosinor analysis indicated no seasonal effect (p = 0.52). Conclusion: The incidence of biopsy-proven GCA remains low in Australia. A higher incidence was noted compared to an earlier study. However, differences in ascertainment and methods of GCA diagnosis may have accounted for the change.

Effects of invisible lip movements on phonetic perception.

We investigated whether 'invisible' visual information, i.e., visual information that is not consciously perceived, could affect auditory speech perception. Repeated exposure to McGurk stimuli (auditory /ba/ with visual [ga]) temporarily changes the perception of the auditory /ba/ into a 'da' or 'ga'. This altered auditory percept persists even after the presentation of the McGurk stimuli when the auditory stimulus is presented alone (McGurk aftereffect). We used this and presented the auditory /ba/ either with or without (No Face) a masked face articulating a visual [ba] (Congruent Invisible) or a visual [ga] (Incongruent Invisible). Thus, we measured the extent to which the invisible faces could undo or prolong the McGurk aftereffects. In a further control condition, the incongruent faces remained unmasked and thus visible, resulting in four conditions in total. Visibility was defined by the participants' subjective dichotomous reports ('visible' or 'invisible'). The results showed that the Congruent Invisible condition reduced the McGurk aftereffects compared with the other conditions, while the Incongruent Invisible condition showed no difference with the No Face condition. These results suggest that 'invisible' visual information that is not consciously perceived can affect phonetic perception, but only when visual information is congruent with auditory information.

The Association between Metabolic Syndrome, Frailty and Disability-Free Survival in Healthy Community-dwelling Older Adults.

OBJECTIVES: To examine the association between metabolic syndrome (MetS) and frailty, and determine whether co-existent MetS and frailty affect disability-free survival (DFS), assessed through a composite of death, dementia or physical disability. DESIGN: Longitudinal study. SETTING AND PARTICIPANTS: Community-dwelling older adults from Australia and the United States (n=18,264) from "ASPirin in Reducing Events in the Elderly" (ASPREE) study. MEASUREMENTS: MetS was defined according to American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines (2018). A modified Fried phenotype and a deficit accumulation Frailty Index (FI) were used to assess frailty. Association between MetS and frailty was examined using multinomial logistic regression. Cox regression was used to analyze the association between MetS, frailty and DFS over a median follow-up of 4.7 years. RESULTS: Among 18,264 participants, 49.9% met the criteria for MetS at baseline. Participants with Mets were more likely to be pre-frail [Relative Risk Ratio (RRR): 1.22; 95%Confidence Interval (CI): 1.14, 1.30)] or frail (RRR: 1.66; 95%CI: 1.32, 2.08) than those without MetS. MetS alone did not shorten DFS while pre-frailty or frailty alone did [Hazard Ratio (HR): 1.68; 95%CI: 1.45, 1.94; HR: 2.65; 95%CI:1.92, 3.66, respectively]. Co-existent MetS with pre-frailty/frailty did not change the risk of shortened DFS. CONCLUSIONS: MetS was associated with pre-frailty or frailty in community-dwelling older individuals. Pre-frailty or frailty increased the risk of reduced DFS but presence of MetS did not change this risk. Assessment of frailty may be more important than MetS in predicting survival free of dementia or physical disability.

Patient-Reported Symptoms of Late Toxicity in Patients With Breast Cancer Treated With Hypofractionated Radiation Therapy and the Association With Quality of Life.

PURPOSE: Our purpose was to assess the prevalence of patient-reported symptoms of local late toxicity in patients with irradiated breast cancer and determine the association between late toxicity and quality of life. METHODS: Within the prospective Utrecht cohort for Multiple BReast cancer intErvention studies and Long-term evaluation cohort, a survey on self-reported late toxicity was sent to all patients with breast cancer with ≥12 months interval since radiation therapy treated with curative intent. Patients were treated with hypofractionated radiation therapy of 40 Gy/15 fractions or 42.5 Gy/16 fractions, with or without a simultaneous integrated boost. Symptoms of late toxicity were evaluated on a 4-point Likert scale. Late toxicity was defined as moderate-severe breast or chest wall pain combined with at least 1 other mild-severe late toxicity symptom, that is, breast or arm/hand lymphedema, firmness of the breast, or impaired arm movement. Physical, role, and social functioning were measured before, during, and after the late toxicity survey using the European Organization for Research and Treatment of Cancer Quality of Life Core questionnaire-C30 and compared with a Dutch normative population. RESULTS: In the study, 1613/2248 patients (72%) were included. Of those, 16% (n = 265) reported late toxicity. The median time interval between radiation therapy and survey was 38 months (interquartile range, 21-55). Moderate/severe firmness of the breast, chest wall pain, and breast pain were reported by, respectively, 18% (n = 295), 14% (n = 225), and 10% (n = 140) of all patients. Physical, role, and social functioning were below the clinical threshold (ie, clinically relevant impairment) in 13% to 52% of patients with late toxicity and 2% to 26% of patients without late toxicity. Patients with late toxicity significantly more often received analgesics, physiotherapy, and lymphedema therapy compared with patients without late toxicity. CONCLUSIONS: This study provided insight into the prevalence of patient-reported late toxicity after hypofractionated radiation therapy and the influence of late toxicity on quality of life after breast cancer. These results may help health care professionals to inform their patients about long-term effects of breast cancer treatment including hypofractionated radiation therapy.

Genicular Nerve Block for Pain Management in Patients With Knee Osteoarthritis: A Randomized Placebo-Controlled Trial.

OBJECTIVE: This study was undertaken to determine the efficacy of ultrasound-guided genicular nerve block (GNB) for the management of knee pain in patients with knee osteoarthritis. METHODS: We performed a 12-week parallel-group, placebo-controlled randomized trial of GNB. Within 2 weeks of randomization, patients with knee osteoarthritis in the active arm received 3 injections of 5.7 mg celestone chronodose (1 ml) and 0.5% bupivacaine (3 ml) to the inferomedial, superomedial, and superolateral genicular nerves; patients with knee osteoarthritis in the placebo arm received injections of normal saline. At baseline and at weeks 2, 4, 8, and 12, patients recorded their pain and disability on a 100-mm visual analog scale (VAS) (the primary outcome measure), the Western Ontario and McMasters Universities Osteoarthritis Index (WOMAC), and the Intermittent and Constant Osteoarthritis Pain scale. Statistical significance was set at a 2-sided Type I error of α = 0.0125 for comparisons at each of the 4 time points. We used a global perceived effect scale to measure patient satisfaction. RESULTS: The 59 patients (36 female, 23 male) who completed the trial had a mean ± SD age of 68.2 ± 8.6 years. Patients in the active group reported improvements in pain scores at 2, 4, 8, and 12 weeks with a diminution of the effect over time. VAS scores at baseline and at weeks 2, 4, 8, and 12 in the active group (n = 31) versus placebo group (n = 28) were 6.2 versus 5.3 (P = 0.294), 2.7 versus 4.7 (P < 0.001), 3.2 versus 5.1 (P < 0.001), 3.9 versus 4.9 (P < 0.001), and 4.6 versus 5.1 (P = 0.055), respectively. Total WOMAC scores at baseline and at weeks 2, 4, 6, 8, and 12 in the active group versus the placebo group were 54.5 versus 48.1 (P = 0.177), 32.9 versus 44.4 (P < 0.001), 33.7 versus 45.8 (P < 0.001), 39.2 versus 44.8 (P = 0.001), and 42.65 versus 45.1 (P = 0.012), respectively. CONCLUSION: GNB offers short-term pain relief for knee osteoarthritis.

A space-based quantum gas laboratory at picokelvin energy scales.

Ultracold quantum gases are ideal sources for high-precision space-borne sensing as proposed for Earth observation, relativistic geodesy and tests of fundamental physical laws as well as for studying new phenomena in many-body physics during extended free fall. Here we report on experiments with the Cold Atom Lab aboard the International Space Station, where we have achieved exquisite control over the quantum state of single 87Rb Bose-Einstein condensates paving the way for future high-precision measurements. In particular, we have applied fast transport protocols to shuttle the atomic cloud over a millimeter distance with sub-micrometer accuracy and subsequently drastically reduced the total expansion energy to below 100 pK with matter-wave lensing techniques.

Effects of structured involvement of the primary care team versus standard care after a cancer diagnosis on patient satisfaction and healthcare use: the GRIP randomised controlled trial.

BACKGROUND: The growing number of cancer survivors and treatment possibilities call for more personalised and integrated cancer care. Primary care seems well positioned to support this. We aimed to assess the effects of structured follow-up of a primary care team after a cancer diagnosis. METHODS: We performed a multicentre randomised controlled trial enrolling patients curatively treated for breast, lung, colorectal, gynaecologic cancer or melanoma. In addition to usual cancer care in the control group, patients randomized to intervention were offered a "Time Out consultation" (TOC) with the general practitioner (GP) after diagnosis, and subsequent follow-up during and after treatment by a home care oncology nurse (HON). Primary outcomes were patient satisfaction with care (questionnaire: EORTC-INPATSAT-32) and healthcare utilisation. Intention-to-treat linear mixed regression analyses were used for satisfaction with care and other continuous outcome variables. The difference in healthcare utilisation for categorical data was calculated with a Pearson Chi-Square or a Fisher exact test and count data (none versus any) with a log-binomial regression. RESULTS: We included 154 patients (control n = 77, intervention n = 77) who were mostly female (75%), mainly diagnosed with breast cancer (51%), and had a mean age of 61 (SD ± 11.9) years. 81% of the intervention patients had a TOC and 68% had HON contact. Satisfaction with care was high (8 out of 10) in both study groups. At 3 months after treatment, GP satisfaction was significantly lower in the intervention group on 3 of 6 subscales, i.e., quality (- 14.2 (95%CI -27.0;-1.3)), availability (- 15,9 (- 29.1;-2.6)) and information provision (- 15.2 (- 29.1;-1.4)). Patients in the intervention group visited the GP practice and the emergency department more often ((RR 1.3 (1.0;1.7) and 1.70 (1.0;2.8)), respectively). CONCLUSIONS: In conclusion, the GRIP intervention, which was designed to involve the primary care team during and after cancer treatment, increased the number of primary healthcare contacts. However, it did not improve patient satisfaction with care and it increased emergency department visits. As the high uptake of the intervention suggests a need of patients, future research should focus on optimizing the design and implementation of the intervention. TRIAL REGISTRATION: GRIP is retrospectively (21/06/2016) registered in the 'Netherlands Trial Register' (NTR5909).

The association of depression and all-cause mortality: Explanatory factors and the influence of gender.

BACKGROUND: The association of depression with mortality and the significance of explanatory factors, in particularly gender, have remained an issue of debate. We therefore aimed to estimate the effect of depression on all-cause mortality, to examine potential explanatory factors and to assess effect modification by gender. METHODS: We used Cox regression models to estimate the effect of depression on mortality based on data from the Gutenberg Health Study, which is a prospective cohort study of the adult population in the districts of Mainz and Mainz-Bingen, Germany. Baseline assessment was between 2007 and 2012. Effect modification by gender was measured on both additive and multiplicative scales. RESULTS: Out of 14,653 participants, 7.7% were depressed according to Patient Health Questionnaire 9 (PHQ-9), and 1,059 (7.2%) died during a median follow-up of 10.7 years. Depression elevated the risk of mortality in men and women in age-adjusted models (HR: 1.41, 95%-CI: 1.03-1.92; resp. HR: 1.96, 95%-CI: 1.43-2.69). Adjustment for social status, physical health and lifestyle covariates attenuated the effect and in the fully-adjusted model the hazard ratio was 0.96 (95%-CI: 0.69-1.33) in men and 1.53 (95%-CI: 1.10-2.12) in women. For effect modification by gender, the measure on multiplicative interaction was 0.68 (95%-CI 0.44-1.07) and on additive interaction was RERI=-0.47 (95%-CI -1.24-0.30). LIMITATIONS: The PHQ-9 is a single self-report measure of depression reflecting symptoms of the past two weeks, limiting a more detailed assessment of depression and course of symptoms, which likely affects the association with mortality. CONCLUSIONS: Depression elevates mortality by multifactorial pathways, which should be taken into account in the biopsychosocially informed treatment of depression. Effect modification by gender was not statistically significant.

Methylphenidate modulates interactions of anxiety with cognition.

While a large body of literature documents the impairing effect of anxiety on cognition, performing a demanding task was shown to be effective in reducing anxiety. Here we explored the mechanisms of this anxiolytic effect by examining how a pharmacological challenge designed to improve attentional processes influences the interplay between the neural networks engaged during anxiety and cognition. Using a double-blind between-subject design, we pharmacologically manipulated working memory (WM) using a single oral dose of 20 mg methylphenidate (MPH, cognitive enhancer) or placebo. Fifty healthy adults (25/drug group) performed two runs of a WM N-back task in a 3 T magnetic resonance imaging scanner. This task comprised a low (1-Back) and high (3-Back) WM load, which were performed in two contexts, safety or threat of shocks (induced-anxiety). Analyses revealed that (1) WM accuracy was overall improved by MPH and (2) MPH (vs. placebo) strengthened the engagement of regions within the fronto-parietal control network (FPCN) and reduced the default mode network (DMN) deactivation. These MPH effects predominated in the most difficult context, i.e., threat condition, first run (novelty of the task), and 3-Back task. The facilitation of neural activation can be interpreted as an expansion of cognitive resources, which could foster both the representation and integration of anxiety-provoking stimuli as well as the top-down regulatory processes to protect against the detrimental effect of anxiety. This mechanism might establish an optimal balance between FPCN (cognitive processing) and DMN (emotion regulation) recruitment.