Theoretically-driven models of suicide have long guided suicidology; however, an approach employing machine learning models has recently emerged in the field. Some have suggested that machine ...learning models yield improved prediction as compared to theoretical approaches, but to date, this has not been investigated in a systematic manner. The present work directly compares widely researched theories of suicide (i.e., BioSocial, Biological, Ideation-to-Action, and Hopelessness Theories) to machine learning models, comparing the accuracy between the two differing approaches. We conducted literature searches using PubMed, PsycINFO, and Google Scholar, gathering effect sizes from theoretically-relevant constructs and machine learning models. Eligible studies were longitudinal research articles that predicted suicide ideation, attempts, or death published prior to May 1, 2020. 124 studies met inclusion criteria, corresponding to 330 effect sizes. Theoretically-driven models demonstrated suboptimal prediction of ideation (wOR = 2.87; 95% CI, 2.65-3.09; k = 87), attempts (wOR = 1.43; 95% CI, 1.34-1.51; k = 98), and death (wOR = 1.08; 95% CI, 1.01-1.15; k = 78). Generally, Ideation-to-Action (wOR = 2.41, 95% CI = 2.21-2.64, k = 60) outperformed Hopelessness (wOR = 1.83, 95% CI 1.71-1.96, k = 98), Biological (wOR = 1.04; 95% CI .97-1.11, k = 100), and BioSocial (wOR = 1.32, 95% CI 1.11-1.58, k = 6) theories. Machine learning provided superior prediction of ideation (wOR = 13.84; 95% CI, 11.95-16.03; k = 33), attempts (wOR = 99.01; 95% CI, 68.10-142.54; k = 27), and death (wOR = 17.29; 95% CI, 12.85-23.27; k = 7). Findings from our study indicated that across all theoretically-driven models, prediction of suicide-related outcomes was suboptimal. Notably, among theories of suicide, theories within the Ideation-to-Action framework provided the most accurate prediction of suicide-related outcomes. When compared to theoretically-driven models, machine learning models provided superior prediction of suicide ideation, attempts, and death.
Application of evidence-based perioperative care protocols reduces complication rates, accelerates recovery and shortens hospital stay. Presently, there are no comprehensive guidelines for ...perioperative care for gastrectomy.
An international working group within the Enhanced Recovery After Surgery (ERAS®) Society assembled an evidence-based comprehensive framework for optimal perioperative care for patients undergoing gastrectomy. Data were retrieved from standard databases and personal archives. Evidence and recommendations were classified according to the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) system and were discussed until consensus was reached within the group. The quality of evidence was rated 'high', 'moderate', 'low' or 'very low'. Recommendations were graded as 'strong' or 'weak'.
The available evidence has been summarized and recommendations are given for 25 items, eight of which contain procedure-specific evidence. The quality of evidence varies substantially and further research is needed for many issues to improve the strength of evidence and grade of recommendations.
The present evidence-based framework provides comprehensive advice on optimal perioperative care for the patient undergoing gastrectomy and facilitates multi-institutional prospective cohort registries and adequately powered randomized trials for further research.
C99 is the transmembrane carboxyl-terminal domain of the amyloid precursor protein that is cleaved by γ-secretase to release the amyloid-β polypeptides, which are associated with Alzheimer's disease. ...Nuclear magnetic resonance and electron paramagnetic resonance spectroscopy show that the extracellular amino terminus of C99 includes a surface-embedded "N-helix" followed by a short "N-loop" connecting to the transmembrane domain (TMD). The TMD is a flexibly curved a helix, making it well suited for processive cleavage by γ-secretase. Titration of C99 reveals a binding site for cholesterol, providing mechanistic insight into how cholesterol promotes amyloidogenesis. Membrane-buried GXXXG motifs (G, Gly; X, any amino acid), which have an established role in oligomerization, were also shown to play a key role in cholesterol binding. The structure and cholesterol binding properties of C99 may aid in the design of Alzheimer's therapeutics.
Quantum bits (qubits) based on individual trapped atomic ions are a promising technology for building a quantum computer. The elementary operations necessary to do so have been achieved with the ...required precision for some error-correction schemes. However, the essential two-qubit logic gate that is used to generate quantum entanglement has hitherto always been performed in an adiabatic regime (in which the gate is slow compared with the characteristic motional frequencies of the ions in the trap), resulting in logic speeds of the order of 10 kilohertz. There have been numerous proposals of methods for performing gates faster than this natural 'speed limit' of the trap. Here we implement one such method, which uses amplitude-shaped laser pulses to drive the motion of the ions along trajectories designed so that the gate operation is insensitive to the optical phase of the pulses. This enables fast (megahertz-rate) quantum logic that is robust to fluctuations in the optical phase, which would otherwise be an important source of experimental error. We demonstrate entanglement generation for gate times as short as 480 nanoseconds-less than a single oscillation period of an ion in the trap and eight orders of magnitude shorter than the memory coherence time measured in similar calcium-43 hyperfine qubits. The power of the method is most evident at intermediate timescales, at which it yields a gate error more than ten times lower than can be attained using conventional techniques; for example, we achieve a 1.6-microsecond-duration gate with a fidelity of 99.8 per cent. Faster and higher-fidelity gates are possible at the cost of greater laser intensity. The method requires only a single amplitude-shaped pulse and one pair of beams derived from a continuous-wave laser. It offers the prospect of combining the unrivalled coherence properties, operation fidelities and optical connectivity of trapped-ion qubits with the submicrosecond logic speeds that are usually associated with solid-state devices.
Background
Enhanced recovery protocols may reduce postoperative complications and length of hospital stay. However, the implementation of these protocols requires time and financial investment. This ...study evaluated the cost‐effectiveness of enhanced recovery implementation.
Methods
The first 50 consecutive patients treated during implementation of an enhanced recovery programme were compared with 50 consecutive patients treated in the year before its introduction. The enhanced recovery protocol principally implemented preoperative counselling, reduced preoperative fasting, preoperative carbohydrate loading, avoidance of premedication, optimized fluid balance, standardized postoperative analgesia, use of a no‐drain policy, as well as early nutrition and mobilization. Length of stay, readmissions and complications within 30 days were compared. A cost‐minimization analysis was performed.
Results
Hospital stay was significantly shorter in the enhanced recovery group: median 7 (interquartile range 5–12) versus 10 (7–18) days (P = 0·003); two patients were readmitted in each group. The rate of severe complications was lower in the enhanced recovery group (12 versus 20 per cent), but there was no difference in overall morbidity. The mean saving per patient in the enhanced recovery group was €1651.
Conclusion
Enhanced recovery is cost‐effective, with savings evident even in the initial implementation period.
Worth the investment
Triple negative breast cancer (TNBC) is a heterogeneous collection of biologically diverse cancers, which contributes to variable clinical outcomes. Previously, we identified a TNBC subtype that has ...a luminal phenotype and expresses the androgen receptor (AR+). TNBC cells derived from these luminal AR + tumors have high frequency phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA) mutations. The purpose of this study was to determine if targeting phosphoinositide 3-kinase (PI3K) alone or in combination with an AR antagonist is effective in AR + TNBC.
We determined the frequency of activating PIK3CA mutations in AR + and AR- TNBC clinical cases. Using AR + TNBC cell line and xenograft models we evaluated the effectiveness of PI3K inhibitors, used alone or in combination with an AR antagonist, on tumor cell growth and viability.
PIK3CA kinase mutations were highly clonal, more frequent in AR + vs. AR- TNBC (40% vs. 4%), and often associated with concurrent amplification of the PIK3CA locus. PI3K/mTOR inhibitors had an additive growth inhibitory effect when combined with genetic or pharmacological AR targeting in AR + TNBC cells. We also analyzed the combination of bicalutamide +/- the pan-PI3K inhibitor GDC-0941 or the dual PI3K/mTOR inhibitor GDC-0980 in xenograft tumor studies and observed additive effects.
While approximately one third of TNBC patients respond to neoadjuvant/adjuvant chemotherapy, recent studies have shown that patients with AR + TNBC are far less likely to benefit from the current standard of care chemotherapy regimens and novel targeted approaches need to be investigated. In this study, we show that activating PIK3CA mutations are enriched in AR + TNBC; and, we show that the growth and viability of AR + TNBC cell line models is significantly reduced after treatment with PI3K inhibitors used in combination with an AR antagonist. These results provide rationale for pre-selection of TNBC patients with a biomarker (AR expression) to investigate the use of AR antagonists in combination with PI3K/mTOR inhibitors.
Abstract
The blood–brain barrier (BBB) presents a significant challenge for targeted drug delivery. A proposed method to improve drug delivery across the BBB is focused ultrasound (fUS), which ...delivers ultrasound waves to a targeted location in the brain and is hypothesized to open the BBB. Furthermore, stem cell-derived exosomes have been suggested as a possible anti-inflammatory molecule that may have neural benefits, if able to pass the BBB. In the present study, transcranial low-intensity focused ultrasound (LIFU), without the use of intravenous microbubbles, was assessed for both (1) its ability to influence the BBB, as well as (2) its ability to increase the localization of intravenously administered small molecules to a specific region in the brain. In vivo rat studies were conducted with a rodent-customized 2 MHz LIFU probe (peak pressure = 1.5 MPa), and injection of labeled stem cell-derived exosomes. The results suggested that LIFU (without microbubbles) did not appear to open the BBB after exposure times of 20, 40, or 60 min; instead, there appeared to be an increase in transcytosis of the dextran tracer. Furthermore, the imaging results of the exosome study showed an increase in exosome localization in the right hippocampus following 60 min of targeted LIFU.
We address the question of minimal requirements for the existence of quantum bound states. In particular, we demonstrate that a few-body system with zero-range momentum-independent two-body ...interactions is unstable against decay into clusters, if mixed-symmetry of its wave function is enforced. We claim that any theory in which the two-body scattering length is much larger than any other scale involved exhibits such instability. We exemplify this with the inability of the leading-order pionless effective field theory to describe stable states of A>4 nuclei. A finite interaction range is identified as a sufficient condition for a bound mixed-symmetry system. The minimal value of this range depends on the proximity of a system to unitarity, on the number of constituents, and on the particular realization of discrete scale invariance of the three-body spectrum.
Background
Spigelian hernias (SpH) belong to the group of eponymous abdominal wall hernias. Major reasons for diagnostic difficulties are its low incidence reaching maximum 2% of abdominal wall ...hernias, a specific anatomical localization with intact external oblique aponeurosis covering the hernia sac and non-constant clinical presentation.
Methods
A literature review was completed to summarize current knowledge on surgical treatment options and results.
Results
SpH presents a high incarceration risk and therefore should be operated upon even if the patient is asymptomatic. Both laparoscopic and open repair approaches are validated by current guidelines with lesser postoperative complications and shorter hospital stay in favour of minimally invasive surgery, regardless of the technique used. Overall recurrence rate is very low.
Conclusion
All diagnosed SpH should be planned for elective operation to prevent strangulated hernia and, therefore emergency surgery. Both open and laparoscopic SpH treatment can be safely performed, depending on surgeon’s experience. In most cases, a mesh repair is generally advised.
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