Explore the vast range of titles available.

Quantum error correction requires the detection of errors via reliable measurements of multiqubit correlation operators. As these operations are inherently faulty, fault-tolerant schemes for realizing quantum error correction are required. Recently, a paradigm requiring only minimal resource overhead in the form of “flag” qubits to detect and correct errors has been proposed. We experimentally demonstrate a fault-tolerant weight-4 parity-check measurement scheme, where one additional flag qubit serves to detect errors, which would otherwise proliferate into uncorrectable weight-2 errors onto the qubit register. We achieve a parity measurement fidelity of 92.3(2)%, which increases to 93.2(2)% upon conditioning to the flag readout result, which shows that the measurement scheme intercepts intrinsic errors occurring throughout the sequence. We show that the protocol is capable of reliably intercepting faults by deliberately injecting bit- and phase-flip errors. For holistic benchmarking of the parity measurement scheme, we use an entanglement witnessing scheme requiring a minimal number of measurements to verify genuine six-qubit multipartite entanglement. The demonstrated fault-tolerant parity measurement scheme constitutes the key building block in a broad class of resource-efficient flag-based quantum error correction protocols including topological color codes. Our hardware platform is based on atomic ions stored in a microchip ion trap. The qubit register is dynamically reconfigured via shuttling operations enabling effective full connectivity without operational cross talk, thereby providing key prerequisites underlying fault-tolerant circuit design. These architectural features in combination with the demonstrated approach to flag-based fault-tolerant quantum error correction open up a route toward scalable fault-tolerant quantum computing.

Protein synthesis activity is abnormally enhanced in cancer cells to support their uncontrolled growth. However, this process needs to be tightly restricted under metabolic stress-a condition often found within the tumor microenvironment-to preserve cell viability. mTORC1 is critical to link protein synthesis activity to nutrient and oxygen levels, in part by controlling the 4E-BP1-eIF4E axis. Whereas mTORC1 and eIF4E are known pro-tumorigenic factors, whose expression or activity is increased in numerous cancers, the role of 4E-BP1 in cancer is not yet definitive. On the one hand, 4E-BP1 has tumor suppressor activity by inhibiting eIF4E and, thus, blocking mRNA translation and proliferation. This is corroborated by elevated levels of phosphorylated and hence inactive 4E-BP1, which are detected in various cancers. On the other hand, 4E-BP1 has pro-tumorigenic functions as it promotes tumor adaptation to metabolic and genotoxic stress by selectively enhancing or preventing the translation of specific transcripts. Here we describe the molecular and cellular functions of 4E-BP1 and highlight the distinct roles of 4E-BP1 in cancer depending on the microenvironmental context of the tumor.

Background Neck of femur fractures result in impaired function for older people. Despite surgery, many patients experience a decrease in functional level and poorer health status after the injury. The objectives of this study were (1) to determine the short-term mobility and hip function of geriatric patients who underwent hip replacement surgery for a displaced neck of femur fracture in our local population and (2) to identify factors which affect the functional outcome of these patients. Methods Patients aged 60 years and above, who were admitted for neck of femur fracture from January 2017 to December 2020, and treated surgically with arthroplasty, were included. Information on patient demography, comorbidities, perioperative data, mobility, hip function and complications were retrospectively collected. Outcome measures used were independent ambulation and recovery of pre-fracture mobility at 1 year after surgery while hip function was assessed using the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) total, pain, stiffness, and physical function scores. Factors associated with these outcomes were analyzed. Results 168 patients with a mean age of 75.2 (SD 8.4) years met the inclusion criteria. 32.1% of patients regained their pre-fracture mobility and 59.6% remained independent 1 year after surgery. Logistic regression analysis identified age, gender, surgical procedure, and time to surgery as significant contributors to recovery of pre-fracture mobility. Older age and increasing requirement for postoperative ambulatory aid resulted in worse WOMAC total and physical function scores. No significant differences were observed in patient-reported hip function between those who had a total hip arthroplasty and those who had a hemiarthroplasty. Conclusion Most geriatric patients with displaced neck of femur fractures did not regain pre-fracture mobility despite surgical treatment with arthroplasty.

Taxane-based radiochemotherapy is a central treatment option for various cancer entities in locally advanced stages. The therapeutic synergism of this combined modality approach due to taxane-mediated radiosensitization of cancer cells is well-known. However, the underlying molecular mechanisms remain largely elusive, and mechanism-derived predictive markers of taxane-based radiochemotherapy are currently not available. Here, we show that clinically relevant doses of Paclitaxel, the prototype taxane, stimulate a tripolar mode of mitosis leading to chromosomal missegregation and aneuploidization rather than interfering with cell cycle progression. This distinct mitotic phenotype was interlinked with Paclitaxel-mediated radiosensitization via overexpression of mitotic Aurora kinase A (AURKA) and its cofactor TPX2 whose knockdown rescued the bipolar mode of cell division and largely attenuated the radiosensitizing effects of Paclitaxel. In the cancer genome atlas (TCGA) lung adenocarcinoma cohort, high expression levels of AURKA and TPX2 were associated with specifically improved overall survival upon taxane-based radiochemotherapy, but not in case of non-taxane-based radiochemotherapy, chemo- or radiotherapy only. Thus, our data provide insights into Paclitaxel-mediated radiosensitization on a mechanistic and molecular level and identify AURKA and TPX2 as the first potential mechanism-based, predictive markers of taxane-based radiochemotherapy.

Since its introduction in the diagnostic manuals DSM-5 and ICD-11, the construct of personality functioning has gained increasing attention. However, it remains unclear which factors might predict improvement in personality functioning. We examined a sample of 648 completed psychodynamic psychotherapies conducted by 172 therapists at the Heidelberg Institute for Psychotherapy. A machine learning approach was used to filter for variables that are relevant for the prediction of the improvement of personality functioning from a broad data set of variables collected at the beginning of each psychodynamic psychotherapy. On average, we found an improvement of 0.24 (SD = 0.48) in the OPD-SQ. This corresponds to a medium effect in the improvement of personality functioning. Patients with initially high impairment experienced particularly large improvements. Overall, we found a large number of variables that proved to be predictive for the improvement of personality functioning. Limitations in social activity due to physical and emotional problems proved to be one of the most important predictors of improvement. Most of the effect sizes were small. Overall, the improvement in personality functioning during psychotherapy is determined more by the sum of a large number of small effects than by individual variables. In particular, variables that capture social areas of life proved to be robust predictors.

Understanding cerebellar–cortical physiological interactions is of fundamental importance to advance the efficacy of neurorehabilitation strategies for patients with cerebellar damage. Previous works have aimed to modulate this pathway by applying transcranial electrical or magnetic stimulation (TMS) over the cerebellum and probing the resulting changes in the primary motor cortex (M1) excitability with motor-evoked potentials (MEPs). While these protocols produce changes in cerebellar excitability, their ability to modulate MEPs has produced inconsistent results, mainly due to the MEP being a highly variable outcome measure that is susceptible to fluctuations in the excitability of M1 neurons and spinal interneurons. To overcome this limitation, we combined TMS with electroencephalography (EEG) to directly record TMS-evoked potentials (TEPs) and oscillations from the scalp. In three sessions, we applied intermittent theta-burst stimulation (iTBS), cathodal direct current stimulation (c-DC) or sham stimulation to modulate cerebellar activity. To assess the effects on M1 and nearby cortex, we recorded TMS-EEG and MEPs before, immediately after (T1) and 15 min (T2) following cerebellar neuromodulation. We found that cerebellar iTBS immediately increased TMS-induced alpha oscillations and produced lasting facilitatory effects on TEPs, whereas c-DC immediately decreased TMS-induced alpha oscillations and reduced TEPs. We also found increased MEP following iTBS but not after c-DC. All of the TMS-EEG measures showed high test–retest repeatability. Overall, this work importantly shows that cerebellar neuromodulation influences both cortical and corticospinal physiological measures; however, they are more pronounced and detailed when utilizing TMS-EEG outcome measures. These findings highlight the advantage of using TMS-EEG over MEPs when assessing the effects of neuromodulation.

Background: Gilles de la Tourette syndrome (GTS) is often complicated by comorbid attention-deficit/hyperactivity disorder (ADHD) or obsessive–compulsive disorder (OCD). This study examines whether motor cortex excitability differs between uncomplicated GTS patients and those complicated by ADHD or OCD. Methods: Motor thresholds, short-interval intracortical inhibition (SICI) and intracortical facilitation (ICF), and short latency afferent inhibition (SAI) were measured using transcranial magnetic stimulation (TMS) in 29 untreated GTS patients (18 uncomplicated, six with comorbid ADHD, five with comorbid OCD) and 24 healthy subjects. Tic severity was rated with standard clinical scales. Results: Patients had slightly higher resting (RMT) and active motor thresholds (AMT). The threshold of SICI and ICF expressed as a percentage of each individual’s AMT was similar in controls and GTS patients. Above threshold, GTS patients had less SICI and more ICF. SICI was similar in all subgroups, but ICF differed significantly between them. Patients with GTS+ADHD had more ICF than controls, uncomplicated GTS patients or GTS+OCD patients; ICF was similar in these other groups. GTS patients as a whole had reduced SAI. Uncomplicated GTS patients or GTS+ADHD patients had less SAI than controls or GTS+OCD patients. Conclusions: GTS with ADHD comorbidity is associated with more extensive changes in the excitability of motor cortex circuits than uncomplicated GTS or GTS+OCD. The extent to which various different neuronal circuits are affected may be relevant for the phenotype of Tourette spectrum disorders.

Patients suffering from fractures are often required to take simvastatin during the bone healing phase due to co-morbidities. However, the impact of simvastatin on fracture healing under ischemic conditions remains unclear so far. Therefore, we analyzed in this study the effect of simvastatin on fracture healing in an established murine ischemia model. Mild ischemia of the right hind limb and a femoral fracture was induced in CD-1 mice. After stabilization of the fracture by an intramedullary screw, the animals received either 30 mg/kg body weight simvastatin per os daily or an equivalent amount of vehicle (control). Bone healing was analyzed by biomechanical as well as radiological, histomorphometric and Western blot analyses 2 and 5 weeks postoperatively. The fractured femurs of both groups exhibited a delayed healing throughout the study period. Bone formation, as assessed by micro-computed tomography, was significantly reduced in the callus tissue of femurs in simvastatin-treated animals compared to controls. Moreover, these femurs showed histomorphometric signs of ongoing healing and a tendency towards less bone tissue at 2 weeks after surgery. Western blot analyses revealed an increased expression of CD31 and phosphoinositide-3-kinase (PI3K) after simvastatin treatment, whereas the expression of bone morphogenetic protein (BMP)-2 was significantly decreased. In conclusion, these results demonstrate that simvastatin impairs fracture healing under challenging ischemic conditions. This effect is most likely caused by an imbalance of angiogenesis and osteogenesis in the callus tissue. These findings indicate that the use of simvastatin during fracture healing under ischemic conditions warrants careful reconsideration in clinical practice.

Background:Primary focal dystonia (PFD) is characterised by motor symptoms. Frequent co-occurrence of abnormal mental conditions has been mentioned for decades but is less well defined. In this study, prevalence rates of psychiatric disorders, personality disorders and traits in a large cohort of patients with PFD were evaluated.Methods:Prevalence rates of clinical psychiatric diagnoses in 86 PFD patients were compared with a population based sample (n = 3943) using a multiple regression approach. Furthermore, participants were evaluated for personality traits with the 5 Factor Personality Inventory.Results:Lifetime prevalence for any psychiatric or personality disorder was 70.9%. More specifically, axis I disorders occurred at a 4.5-fold increased chance. Highest odds ratios were found for social phobia (OR 21.6), agoraphobia (OR 16.7) and panic disorder (OR 11.5). Furthermore, an increased prevalence rate of 32.6% for anxious personality disorders comprising obsessive–compulsive (22.1%) and avoidant personality disorders (16.3%) were found. Except for social phobia, psychiatric disorders manifested prior to the occurrence of dystonia symptoms. In the self-rating of personality traits, PFD patients demonstrated pronounced agreeableness, conscientiousness and reduced openness.Conclusions:Patients with PFD show distinct neuropsychiatric and personality profiles of the anxiety spectrum. PFD should therefore be viewed as a neuropsychiatric disorder rather than a pure movement disorder.

Fractures of the clavicle are among the most common fractures. They typically result from a fall onto the lateral shoulder or the extended arm and are often related to sports and bicycle accidents. Obtaining the exact trauma mechanism, proper clinical findings and adequate X‑rays usually lead to the correct diagnosis. Non-displacement fractures can be treated conservatively with good results. Unstable and displaced fractures should be treated operatively. Open fractures or looming penetration are emergencies und should be treated immediately. In addition to fracture classification and morphology, other factors such as additional injuries and patient-related factors need to be considered in order to make an individualized therapy decision. In operative treatment, angular stable plating is the therapy of choice, and in most cases early functional aftercare is possible.