Understanding MOF Flexibility: An Analysis Focused on Pillared Layer MOFs as a Model System.

Flexible porous frameworks are at the forefront of materials research. A unique feature is their ability to open and close their pores in an adaptive manner induced by chemical and physical stimuli. Such enzyme-like selective recognition offers a wide range of functions ranging from gas storage and separation to sensing, actuation, mechanical energy storage and catalysis. However, the factors affecting switchability are poorly understood. In particular, the role of building blocks, as well as secondary factors (crystal size, defects, cooperativity) and the role of host-guest interactions, profit from systematic investigations of an idealized model by advanced analytical techniques and simulations. The review describes an integrated approach targeting the deliberate design of pillared layer metal-organic frameworks as idealized model materials for the analysis of critical factors affecting framework dynamics and summarizes the resulting progress in their understanding and application.

Transition from Homochiral Clusters to Racemate Monolayers during 2D Crystallization of Trioxa[11]helicene on Ag(100).

The front cover artwork is provided by Prof. Ernst from Empa. The image shows determination of the sense of helicity of trioxa[11]helicene enantiomers with an atomic force microscope, which allows discrimination between homo- and heterochiral 2D self-assembly. Read the full text of the Article at 10.1002/cphc.202000853.

Transition from Homochiral Clusters to Racemate Monolayers during 2D Crystallization of Trioxa[11]helicene on Ag(100).

The phenomenon of chiral crystallization into homochiral crystals is known for more than 170 years, yet it is still poorly understood. Studying crystallization on surfaces under well-defined condition seems a promising approach towards better understanding the intermolecular chiral recognition mechanisms during nucleation and growth. The two-dimensional aggregation of racemic trioxaundecahelicene on the single crystalline silver(100) surface has been investigated with scanning tunneling microscopy and with non-contact atomic force microscopy, as well as molecular modeling simulations. A transition from homochiral cluster motifs to heterochiral assembly into large islands with increasing coverage is observed. Force field modelling confirms higher stability of heterochiral arrangements from twelve molecules on. Results are discussed with respect to previous findings for the all-carbon heptahelicene on the same surface.

Large Converse Piezoelectric Effect Measured on a Single Molecule on a Metallic Surface.

The converse piezoelectric effect is a phenomenon in which mechanical strain is generated in a material due to an applied electrical field. In this work, we demonstrate the converse piezoelectric effect in single heptahelicene-derived molecules on the Ag(111) surface using atomic force microscopy (AFM) and total energy density functional theory (DFT) calculations. The force-distance spectroscopy acquired over a wide range of bias voltages reveals a linear shift of the tip-sample distance at which the contact between the molecule and tip apex is established. We demonstrate that this effect is caused by the bias-induced deformation of the spring-like scaffold of the helical polyaromatic molecules. We attribute this effect to coupling of a soft vibrational mode of the molecular helix with a vertical electric dipole induced by molecule-substrate charge transfer. In addition, we also performed the same spectroscopic measurements on a more rigid o-carborane dithiol molecule on the Ag(111) surface. In this case, we identify a weaker linear electromechanical response, which underpins the importance of the helical scaffold on the observed piezoelectric response.

Force-Driven Single-Atom Manipulation on a Low-Reactive Si Surface for Tip Sharpening.

A single atomic manipulation on the delta-doped B:Si(111)-(√3x√3)R30° surface using a low temperature dynamic atomic force microscopy based on the Kolibri sensor is investigated. Through a controlled vertical displacement of the probe, a single Si adatom in order to open a vacancy is removed. It is shown that this process is completely reversible, by accurately placing a Si atom back into the vacancy site. In addition, density functional theory simulations are carried out to understand the underlying mechanism of the atomic manipulation in detail. This process also rearranges the atoms at the tip apex, which can be effectively sharpened in this way. Such sharper tips allow for a deeper look into the Si adatom vacancy site. Namely, high-resolution images of the vacancy showing subsurface Si dangling bond triplets, which surround the substitutional B dopant atom in the first bilayer, are achieved.

Reduced thermal expansion by surface-mounted nanoparticles in a pillared-layered metal-organic framework.

Control of thermal expansion (TE) is important to improve material longevity in applications with repeated temperature changes or fluctuations. The TE behavior of metal-organic frameworks (MOFs) is increasingly well understood, while the impact of surface-mounted nanoparticles (NPs) on the TE properties of MOFs remains unexplored despite large promises of NP@MOF composites in catalysis and adsorbate diffusion control. Here we study the influence of surface-mounted platinum nanoparticles on the TE properties of Pt@MOF (Pt@Zn2(DP-bdc)2dabco; DP-bdc2-=2,5-dipropoxy-1,4-benzenedicarboxylate, dabco=1,4-diazabicyclo[2.2.2]octane). We show that TE is largely retained at low platinum loadings, while high loading results in significantly reduced TE at higher temperatures compared to the pure MOF. These findings support the chemical intuition that surface-mounted particles restrict deformation of the MOF support and suggest that composite materials exhibit superior TE properties thereby excluding thermal stress as limiting factor for their potential application in temperature swing processes or catalysis.

Interactive, case-based seminars in the digitized pediatrics block internship from the students' perspective.

We report on the pediatric block practice digitized due to the COVID-19 pandemic. Nineteen seminars were recorded, which represent the broad spectrum of pediatrics as comprehensively as possible, and made available on the learning platform ILIAS in a learning sequence. In order to increase attention and learning success formative questions were interspersed into the seminars. The evaluation of the students showed a high acceptance of this course. Especially the formative questions and the high time flexibility were appreciated. A major point of criticism was that not all questions were resolved immediately afterwards. The resolutions were inserted in the meantime. Parts of the digitized block practical course should therefore be used in the pediatric block practical course after the end of the corona restrictions after appropriate revision.

Long-term effect of rehabilitation in coronary artery disease patients: randomized clinical trial of the impact of exercise volume.

OBJECTIVE: To assess whether exercise volume during phase II rehabilitation affects long-term clinical benefits in patients with coronary artery disease. DESIGN: Prospective randomized clinical trial with long-term follow-up. SETTING: Hospital outpatient clinic. SUBJECTS: Coronary artery disease patients (age 65 +/- 9 years, 82% males) attending a phase II rehabilitation programme were randomized into two groups of exercise volumes: 40- versus 60-minute training sessions. Patients exercised for three days per week for seven weeks, at 65% of baseline oxygen uptake capacity. Next, they were followed up for 18 months. Out of 165 patients with coronary artery disease who completed the exercise intervention, 119 attended the 18-month follow-up assessment. MAIN MEASUREMENTS: Body anthropometrics, resting haemodynamics, blood lipid profile, glycaemia, and C-reactive protein level, smoking behaviour, habitual physical activity, cardiovascular disease incidence and mortality. RESULTS: In total population, a significant worsening of various cardiovascular disease risk factors was found at 18 months follow-up (P<0.05), and few patients (27% of total group) adhered to the recommended minimal physical activity level. No difference in change of body anthropometrics, resting haemodynamics, blood lipid profile, glycaemia, and C-reactive protein level, and smoking behaviour was seen between different exercise volumes (P>0.05). In addition, total cardiovascular disease incidence (13% versus 22% in 40- versus 60-minute group, respectively) and habitual physical activity were not different between groups (P>0.05). CONCLUSION: In patients with coronary artery disease following cardiac rehabilitation, the cardiovascular disease risk profile worsened significantly during long-term follow-up. A smaller exercise volume during phase II rehabilitation generated equal long-term clinical benefits compared to a greater exercise volume.

Neuromuscular electrical stimulation as a possible means to prevent muscle tissue wasting in artificially ventilated and sedated patients in the intensive care unit: A pilot study.

OBJECTIVE: The aim of this study was to explore if electrical stimulation could prevent muscle atrophy. MATERIAL AND METHODS: Patients were hospitalized for postoperative coronary artery bypass graftin, chronic obstructive pulmonary disease, ventilatory failure, or acute cerebro-vascular accident, and were divided into an intervention group or a control group. The intervention group underwent daily 30 minute training with an intermittent neuromuscular electrical stimulation applied to the right quadriceps muscle. Heart rate, respiration rate, systolic and diastolic blood pressure, and oxygen saturation were monitored before, during, and after electrical stimulation. Circumference of both thighs was measured. RESULTS: The intervention resulted in a significant reduction of muscle atrophy in the stimulated as compared with the non-stimulated limb (p < 0.05), without making any impact on cardiovascular, respiratory and, hemodynamic characteristics. CONCLUSIONS: Muscle atrophy is prevented by intermittent neuromuscular electrical stimulation while this intervention showed no obvious impact on the cardio-respiratory conditions of the patients.

Quantum dissipation driven by electron transfer within a single molecule investigated with atomic force microscopy.

Intramolecular charge transfer processes play an important role in many biological, chemical and physical processes including photosynthesis, redox chemical reactions and electron transfer in molecular electronics. These charge transfer processes are frequently influenced by the dynamics of their molecular or atomic environments, and they are accompanied with energy dissipation into this environment. The detailed understanding of such processes is fundamental for their control and possible exploitation in future technological applications. Most of the experimental studies of the intramolecular charge transfer processes so far have been carried out using time-resolved optical spectroscopies on large molecular ensembles. This hampers detailed understanding of the charge transfer on the single molecular level. Here we build upon the recent progress in scanning probe microscopy, and demonstrate the control of mixed valence state. We report observation of single electron transfer between two ferrocene redox centers within a single molecule and the detection of energy dissipation associated with the single electron transfer.

Thermal Defect Engineering of Precious Group Metal-Organic Frameworks: A Case Study on Ru/Rh-HKUST-1 Analogues.

A methodology is introduced for controlled postsynthetic thermal defect engineering (TDE) of precious group metal-organic frameworks (PGM-MOFs). The case study is based on the Ru/Rh analogues of the archetypical structure [Cu3(BTC)2] (HKUST-1; BTC = 1,3,5-benzenetricarboxylate). Quantitative monitoring of the TDE process and extensive characterization of the samples employing a complementary set of analytical and spectroscopic techniques reveal that the compositionally very complex TDE-MOF materials result from the elimination and/or fragmentation of ancillary ligands and/or linkers. TDE involves the preferential secession of acetate ligands, intrinsically introduced via coordination modulation during synthesis, and the gradual decarboxylation of ligator sites of the framework linker BTC. Both processes lead to modified Ru/Rh paddlewheel nodes. These nodes exhibit a lowered average oxidation state and more accessible open metal centers, as deduced from surface-ligand IR spectroscopy using CO as a probe and supported by density functional theory (DFT)-based computations. The monometallic and the mixed-metal PGM-MOFs systematically differ in their TDE properties and, in particular in the hydride generation ability (HGA). This latter property is an important indicator for the catalytic activity of PGM-MOFs, as demonstrated by the ethylene dimerization reaction to 1-butene.

Reduction of cardiovascular event rate: different effects of cardiac rehabilitation in CABG and PCI patients.

OBJECTIVE: In coronary artery disease, the implementation of a cardiac rehabilitation (CR) programme favourably affects cardiovascular prognosis. However, it remains uncertain whether patients benefit to a similar extent from CR after coronary artery bypass graft surgery (CABG) or percutaneous coronary intervention (PCI). In this study, we have assessed whether CR is equally effective for suppressing the two-year cardiovascular event incidence after CABG or PCI. METHODS AND RESULTS: 194 PCI and 149 CABG patients participated in a three-month CR programme, while 245 PCI and 89 CABG patients received standard care. After the completion of CR during a two-year follow-up, data on cardiovascular risk factors, medication and cardiovascular events (repeat coronary revascularisation, acute myocardial infarction, and death) were collected from hospital files. Both CABG and PCI patients included into CR showed a significantly lower mortality, as compared to control patients (0.6% vs. 4.2%, P < 0.05). However, total cardiovascular disease incidence was significantly lower as a result of CR in CABG patients (4.7% vs. 14.0%, P < 0.05), but not in PCI patients (19.1% vs. 22.4%, P > 0.05). CONCLUSION: When following a similar 3-month cardiac rehabilitation programme, the reduction of cardiovascular disease incidence during 2 years of follow-up is different between PCI and CABG patients.

Pseudodystrophy of the ankle and lower leg in a 9-year-old girl.

A 9-year-old girl presented with pain, swelling, redness and functional impairment of the left foot after a minor trauma. Clinical assessment revealed atrophy of the left calf and cyanosis and coldness of the left foot. Bone scintigraphy showed diffusely decreased tracer uptake in the left lower leg. Further examinations were normal. Pseudodystrophy was diagnosed and intensive physiotherapy was started. This resulted in complete functional recovery. Pseudodystrophy is typically found in children, adolescents and young women. The clinical features usually include severe pain at a joint or part of a limb with major functional disability, cyanosis, coldness and oedema or atrophy. This is caused by disuse of the affected limb after a minor trauma. The physical lesions may be improved or cured by means of intensive physiotherapy, sometimes combined with medication. As psychogenic factors often play an important role, one of the important elements of treatment is psychotherapy. The most important differential diagnosis is reflex sympathetic dystrophy (RSD). The distinction can be made by bone scintigraphy.

Long-term cost-benefit ratio of cardiac rehabilitation after percutaneous coronary intervention.

OBJECTIVE: Cardiac rehabilitation (CR) has been shown to reduce short-term mortality and morbidity after percutaneous coronary intervention (PCI). Nonetheless, the long-term effects of CR after PCI and its cost-benefit ratio are not well studied. This study analyses the effect of multidisciplinary, hospital-based, ambulatory CR on long-term health-related costs after PCI. METHODS AND RESULTS: 213 patients were studied after PCI: 133 patients referred to cardiac rehabilitation were compared with 80 patients who were referred for PCI from another hospital, where no rehabilitation was available. The hospital files of these patients were studied and the patient and/or his/her general practitioner were contacted by telephone after a follow-up of approximately 4.5 years. All cardiovascular events (recurrent angina, coronary revascularization, acute myocardial infarction, and death) were noted and their cost to the community was calculated. Compared to no CR, CR resulted in a significant reduction of hospitalizations for angina (75% vs. 45%), and coronary revascularizations (17% vs. 7%). There was a significant increase in the incidence of myocardial infarction (2.5% vs. 7.5%). The intervention group experienced a total of 0.93 events/patient, as compared to 1.52 events/patient in the control group. The total health care cost (including the cost of CR) at 4.5 years of follow-up was lower in the rehabilitation group compared to the control group (4,862 Euro/patient vs. 5,498 Euro/patient). CONCLUSION: Cardiac rehabilitation after PCI not only significantly reduces the number of cardiac events, but, despite the additional cost due to CR, results in cost savings from the Belgian health care payer's perspective.

Understanding and improving value frameworks with real-world patient outcomes.

OBJECTIVES: To provide recommendations that will improve approaches to measuring the value of new medical technologies to patients. STUDY DESIGN: Informed discussion by experts after literature review. METHODS: A working group was formed, and participants discussed how value frameworks should incorporate key features important to patients in evaluating new medical technologies, particularly for chronic diseases. RESULTS: The working group suggests that new value frameworks should integrate real-world evidence to complement randomized controlled trials, incorporate the ways in which real-world behavior mediates outcomes, and explicitly discuss how therapies affect real-world equity and disparities in care. CONCLUSIONS: Collective stakeholders that include key decision makers within our healthcare system need to recognize the importance of implementing real-world evidence and devote resources to further research into the chronic disease areas in which the impact of human behavior is amplified by the duration of disease and treatment.

The effects of exercise training on fat-mass loss in obese patients during energy intake restriction.

Dietary restriction combined with endurance exercise training represents an effective strategy to promote weight loss and reduce fat mass in obese patients. Exercise programmes without dietary restriction are less efficient. However, addition of exercise to a dietary restriction programme does not induce a greater fat-mass loss than dietary restriction alone. The latter is likely attributed to a compensatory reduction in daily physical activity following the implementation of exercise training. Nonetheless, inclusion of an exercise training programme is important to prevent a decrease in fat-free mass, increase relative visceral fat-mass loss, improve dietary compliance and eventually maintain long-term weight control. Obese male patients with the highest fat mass are most likely to lose the largest amount of fat mass in such lifestyle intervention programmes. Influences of training modalities during energy intake restriction on fat-mass loss are reviewed. The relationship between total energy expenditure during exercise training and overall fat-mass loss has been firmly established. The amount of training forms a more important predictor of fat-mass loss than training intensity. The sort of exercise (e.g. walking, cycling, swimming) plays another important predictor of fat-mass loss in intervention programmes. The implementation of resistance training in such programmes does not augment fat-mass loss but improves body composition by increasing fat-free mass. Further studies are needed to define the optimal interventional programme for obese patients.

Fatigue in the U.S. workforce: prevalence and implications for lost productive work time.

OBJECTIVE: The objective of this study was to estimate fatigue prevalence and associated health-related lost productive time (LPT) in U.S. workers. METHODS: Fatigue prevalence, LPT due to fatigue, and LPT for any health-related reason (in hours and dollars) were measured in a national cross-sectional telephone survey of U.S. workers. RESULTS: The 2-week period prevalence of fatigue was 37.9%. Of workers with fatigue, 65.7% reported health-related LPT compared with 26.4% of those without fatigue. Workers with fatigue cost employers 136.4 billion dollars annually in health-related LPT, an excess of 101.0 billion dollars compared with workers without fatigue. Fatigue frequently co-occurs with other conditions and, when present, is associated with a threefold increase, on average, in the proportion of workers with condition-specific LPT. CONCLUSIONS: Fatigue is prevalent in the U.S. workforce. When occurring with other health conditions, it is associated with significantly more condition-specific LPT.

The importance of an exercise testing protocol for detecting changes of peak oxygen uptake in cardiac rehabilitation.

OBJECTIVE: To assess which exercise testing protocol is most sensitive for assessing peak oxygen uptake (VO2peak) changes as a result of cardiac rehabilitation. DESIGN: Prospective randomized clinical trial. SETTING: Outpatient cardiac rehabilitation center. PARTICIPANTS: Forty-two cardiac patients (33 men; mean age, 65.4+/-8.4 y). INTERVENTION: All patients were included into a 7-week cardiac rehabilitation program and randomized in 2 subgroups. One group of patients was evaluated by a 1-minute stage (n=21) and another group by a 3-minute stage (n=21) exercise testing protocol. MAIN OUTCOME MEASURES: In both groups, maximal cardiopulmonary exercise tests on a bicycle with analysis of VO2peak, expiratory volume (VE), respiratory exchange ratio, heart rate, cycling resistance (W), and test duration were performed at the start and end of the program. RESULTS: Subgroups were closely matched, and no changes in beta-blocker treatment occurred during this study. As result of the rehabilitation program, total test duration and Wpeak improved significantly in both groups (P<.05). Nonetheless, VO2peak and VEpeak increased significantly in the 1-minute stage duration group (P<.05) but not in the 3-minute stage duration group (P>.05). In addition, the change of VO2peak, VEpeak, and total test duration was significantly greater in the 1-minute stage duration group compared with the 3-minute stage duration group (P<.05). CONCLUSIONS: For detecting changes of VO2peak as result of cardiac rehabilitation, a 1-minute stage exercise testing protocol is more sensitive when compared with a 3-minute stage exercise testing protocol.

Administrative claims analysis of the relationship between warfarin use and risk of hemorrhage including drug-drug and drug-disease interactions.

BACKGROUND: Despite the risk of hemorrhage, warfarin is the most commonly used oral anticoagulant today, both as monotherapy and when taken in combination with selected drugs. Warfarin is used most commonly for irregular heartbeat, after a heart attack, and after joint or heart valve replacement surgery. OBJECTIVE: To evaluate the relative risk of hemorrhage in health plan members who received warfarin concomitant with a drug known to cause an interaction or after diagnosis of liver disease or heart failure (HF). METHODS: A cohort study sample was drawn from an administrative database comprising medical and pharmacy claims for 1.7 million health plan members. A health plan member was defined as anyone who was eligible for pharmacy and medical benefits at any time from October 1, 2003, to September 30, 2004. To be included in the study, a member must have received at least 1 pharmacy claim for warfarin during the study period and been younger than 100 years. Hemorrhage was defined as a diagnosed bleeding episode recorded on a medical claim within 7 calendar days of a fill date for a pharmacy claim (new or refill) for warfarin. The following variables were used to predict the outcome measures: type of drug-drug or drug-disease interaction, patient age and gender, number of unique prescribers during the year for all drugs, specialty of the first prescriber for warfarin, average dose of warfarin, and days of warfarin therapy. Because individuals were followed only during the calendar year under study, the authors have interpreted the days of therapy measured primarily as a control on exposure. The outcome measures are prevalence of drug and disease interactions among members receiving warfarin therapy and the per-patient-per-year and per-member-per-month (PMPM) cost of medical treatment of hemorrhage associated with warfarin therapy including drug and disease interactions. Costs are defined as the total paid amount for a procedure or service after negotiated provider discounts and subtraction of patient copay and deductibles. Logistic regression was used to evaluate the relative risk of hemorrhage in users of warfarin monotherapy and of warfarin users with drug-drug and drug-disease interactions. The comparison group in the logistic regression comprised the members who were not diagnosed with either HF or liver disease and who received warfarin therapy but none of the drugs under study known to cause drug interactions. Therefore, the odds ratios [ORs] produced were estimates of the relative risk of hemorrhage when taking warfarin concomitant with selected drugs and diseases. RESULTS: Of the 17,895 patients who used warfarin during the study year, 2,634 (14.7%) were diagnosed with a hemorrhage event within 1 week after filling a prescription for warfarin. The factors associated with an increased risk of hemorrhage included female gender (OR 1.149; 95% confidence interval [CI], 1.053- 1.253), liver disease (OR 1.764; 95% CI, 1.360-2.288), and HF (OR 1.559; 95% CI, 1.373-1.770). Compared with the use of warfarin alone, the use of either cephalosporins (OR 1.157; 95% CI, 1.043-1.285) or metronidazole (OR 1.578; 95% CI, 1.321-1.886) was associated with increased risk of hemorrhage, whereas the risk of hemorrhage was not greater for concomitant use of warfarin with amiodarone, fibric acid derivatives, or nonsteroidal anti-inflammatory drugs (NSAIDs), including cyclooxygenase-2 (COX-2) inhibitors. There was no relationship between estimated average daily warfarin dose and prevalence of hemorrhage. Other variables associated with an increased risk of hemorrhage were increased patient age, female gender, 120 days or more of warfarin therapy during the year, 2 or more unique prescriber numbers, and the medical specialty of the first prescriber of warfarin. Over the population of 1.7 million members, the cost for all hemorrhage events within 7 days of a pharmacy claim for warfarin was 0.40 dollars PMPM. CONCLUSIONS: Only 2 of 5 combinations of warfarin with drugs in this study were found to be associated with a higher prevalence of hemorrhage compared with warfarin use alone. The absolute prevalence of hemorrhage in users of warfarin and metronidazole was 22.7% and 17.2% for warfarin and cephalosporins, respectively, versus 14.2% in users of warfarin alone. The prevalence of hemorrhage for concomitant use of warfarin and NSAIDs/COX-2 inhibitors, amiodarone, or fibric acid derivatives such as fenofibrate was not greater than for warfarin alone. Liver disease or HF in warfarin users was associated with a significant increase in the likelihood of hemorrhage.