Non-physical practice improves task performance in an unstable, perturbed environment: motor imagery and observational balance training

For consciously performed motor tasks executed in a defined and constant way, both motor imagery (MI) and action observation (AO) have been shown to promote motor learning. It is not known whether these forms of non-physical training also improve motor actions when these actions have to be variably applied in an unstable and unpredictable environment. The present study therefore investigated the influence of MI balance training (MI_BT) and a balance training combining AO and MI (AO+MI_BT) on postural control of undisturbed and disturbed upright stance on unstable ground. As spinal reflex excitability after classical (i.e., physical) balance training (BT) is generally decreased, we tested whether non-physical BT also has an impact on spinal reflex circuits. Thirty-six participants were randomly allocated into an MI_BT group, in which participants imagined postural exercises, an AO+MI_BT group, in which participants observed videos of other people performing balance exercises and imagined being the person in the video, and a non-active control group (CON). Before and after 4 weeks of non-physical training, balance performance was assessed on a free-moving platform during stance without perturbation and during perturbed stance. Soleus H-reflexes were recorded during stable and unstable stance. The post-measurement revealed significantly decreased postural sway during undisturbed and disturbed stance after both MI_BT and AO+MI_BT. Spinal reflex excitability remained unchanged. This is the first study showing that non-physical training (MI_BT and AO+MI_BT) not only promotes motor learning of “rigid” postural tasks but also improves performance of highly variable and unpredictable balance actions. These findings may be relevant to improve postural control and thus reduce the risk of falls in temporarily immobilized patients

The impact of preprinted prescription forms on medication prescribing errors in an ophthalmology clinic in northeast Thailand: a non-randomised interventional study

Objectives: To understand the incidence and types of medication prescribing errors in a low resource setting ophthalmology clinic and to determine the impact of a preprinted prescription based on the hospital formulary (FormularyScript) on medication prescribing errors. Design: Non-randomised interventional study. Setting: Ophthalmology clinic in a teaching hospital in northeast Thailand. Participants: 4349 handwritten prescriptions collected from October 2009 to December 2009, and 4146 FormularyScripts collected from February 2010 to May 2010. Primary and Secondary Outcome Measures: All prescriptions from the handwritten and FormularyScript groups were analysed for medication error rates by types (legibility, ambiguous, incomplete, abbreviation and accuracy) and subtypes (drug name, strength, which eye, route and dispensed amount). Results: Comparison of error rates in the two groups showed a 10-fold reduction in the overall error rate using FormularyScript (32.9%–3.5%, p<0.001). FormularyScripts were associated with statistically significant (p<0.001) decreases in the following error types: legibility (16.1%–0.1%), incomplete (16.1%–0.1%) and abbreviation (3.1%–0.3%). There was no statistically significant change in accuracy errors (0.8%–0.6%, p=0.21). Ambiguous errors increased with FormularyScripts (0.6%–2.5%, p<0.001), likely due to the introduction of new ways to make errors. Decreases were seen in all legibility, abbreviation and accuracy error subtypes, and four out of six incomplete error subtypes. There were statistically significant increases in both ambiguous error subtypes: which eye (0.3%–2.5%, p<0.001) and drug name (0.3%–0.6%, p=0.03). Conclusions: In our study population, outpatient medication prescribing errors were common and primarily due to legibility and incomplete error types. A preprinted prescription form has the potential to decrease medication prescribing errors related to legibility, incomplete prescribing information and use of unacceptable abbreviations without changing the overall rate of accuracy errors. However, new error types can occur

Complication rates of peripherally inserted central catheters vs implanted ports in patients receiving systemic anticancer therapy: A retrospective cohort study

While implanted port catheters ("PORTs") have historically been the standard device for intravenous systemic anticancer therapy, the use of peripherally inserted central catheters (PICCs) has increased continuously and reliable catheter selection guidelines are lacking. We compare complication rates of PORTs and PICCs in cancer treatment in a retrospective study of 3365 patients with both solid organ (n = 2612) and hematologic (n = 753) malignancies, between 2001 and 2021. 26.4% (n = 890) of all patients were treated via PICCs and 73.6% (2475) via PORTs. 20.7% (578) experienced a major catheter-related complication with a higher rate in PICCs than in PORTs (23.5% vs 14.9%, P < .001). Among major complications, infections and mechanical complications were more common in PICCs than in PORTs (11.9% vs 6.4%, P = .001, 7.3% vs 4.2%, P = .002), whereas the rate of thrombosis was similar (3.4% vs 3.0%, P = .9). While PORTs had a higher rate of periprocedural complications (2.7% vs 1.1%, P < .05), PICCs overall complication rate exceeded PORTs within 3 days from implantation. Median follow-up was 49 (PICC) and 60 weeks (PORT). PORTs are safer and therefore should be preferred in this setting regardless of catheter dwell time

IronFleet: Proving Practical Distributed Systems Correct

Abstract Distributed systems are notorious for harboring subtle bugs. Verification can, in principle, eliminate these bugs a priori, but verification has historically been difficult to apply at fullprogram scale, much less distributed-system scale. We describe a methodology for building practical and provably correct distributed systems based on a unique blend of TLA-style state-machine refinement and Hoare-logic verification. We demonstrate the methodology on a complex implementation of a Paxos-based replicated state machine library and a lease-based sharded key-value store. We prove that each obeys a concise safety specification, as well as desirable liveness requirements. Each implementation achieves performance competitive with a reference system. With our methodology and lessons learned, we aim to raise the standard for distributed systems from &quot;tested&quot; to &quot;correct.&quot

The Association for Human Pharmacology in the Pharmaceutical Industry London Meeting October 2019: Impending Change, Innovation, and Future Challenges

The Association for Human Pharmacology in the Pharmaceutical Industry (AHPPI) annual meeting focused on impending change, innovation, and future challenges facing early phase drug development as we move into the second decade of the 21th century. The meeting opened with discussion around the technical revolution in pharmaceutical medicine over the 4 decades since the AHPPI was founded and how transformative technologies have accompanied the introduction of processes such as physiologically based pharmacokinetic modeling. During the meeting examples were presented of how in terms of the development of new therapies, the classic phases of clinical drug development are becoming a thing of the past and the lines between the phases have begun to blur, particularly in the field of oncology. The contribution that monoclonal antibodies have made to medicine and the next chapter in their design and use was also discussed. A representative of the UK’s Medicine and Healthcare Products Regulatory Agency discussed the increasing numbers of requests to approve complex innovative design trials, how novel trial designs are impacting on the traditional linear “phase” approach to drug development and the common pitfalls associated with them. Guidance was provided from a regulator’s viewpoint on what was meant by the term “novel design” and how to submit successful trial applications for such complex trials. In an Oxford-style debate, the audience discussed the motion that “there is no longer a need to include placebo subjects in early clinical trials.” The keynote speaker focused on delivering change in complex environments such as the field of drug development. The afternoon session included presentations on the challenges associated with drug product design, the complexities within non-oral dosage forms and proposed new methods of formulations for drug delivery. Presentations were also given on advances in mechanistic and computational pharmacokinetic modeling and how they have proved to be valuable tools to rationalize and facilitate the process of drug development

The Association for Human Pharmacology in the Pharmaceutical Industry London Meeting October 2019: Impending Change, Innovation, and Future Challenges.

The Association for Human Pharmacology in the Pharmaceutical Industry (AHPPI) annual meeting focused on impending change, innovation, and future challenges facing early phase drug development as we move into the second decade of the 21th century. The meeting opened with discussion around the technical revolution in pharmaceutical medicine over the 4 decades since the AHPPI was founded and how transformative technologies have accompanied the introduction of processes such as physiologically based pharmacokinetic modeling. During the meeting examples were presented of how in terms of the development of new therapies, the classic phases of clinical drug development are becoming a thing of the past and the lines between the phases have begun to blur, particularly in the field of oncology. The contribution that monoclonal antibodies have made to medicine and the next chapter in their design and use was also discussed. A representative of the UK's Medicine and Healthcare Products Regulatory Agency discussed the increasing numbers of requests to approve complex innovative design trials, how novel trial designs are impacting on the traditional linear "phase" approach to drug development and the common pitfalls associated with them. Guidance was provided from a regulator's viewpoint on what was meant by the term "novel design" and how to submit successful trial applications for such complex trials. In an Oxford-style debate, the audience discussed the motion that "there is no longer a need to include placebo subjects in early clinical trials." The keynote speaker focused on delivering change in complex environments such as the field of drug development. The afternoon session included presentations on the challenges associated with drug product design, the complexities within non-oral dosage forms and proposed new methods of formulations for drug delivery. Presentations were also given on advances in mechanistic and computational pharmacokinetic modeling and how they have proved to be valuable tools to rationalize and facilitate the process of drug development

High β-1,4-Galactosyltransferase-I expression in peripheral T-lymphocytes is associated with a low risk of relapse in germ-cell cancer patients receiving high-dose chemotherapy with autologous stem cell reinfusion.

Survival of patients with germ-cell cancer (GCC) and primary progression or relapse after cisplatin-based first-line chemotherapy is highly heterogeneous, ranging from close to zero to more than 70%. We investigated β-1,4-Galactosyltransferase-I () expression levels in peripheral lymphocytes in a cohort of 46 testicular cancer patients. enhances immune cell crosstalk via glycosylation of surface molecules. A high expression level of in T-lymphocytes, but not in monocytes, was associated with a lower risk of relapse with a hazard ratio (HR) of 0.66 (95% confidence interval (CI) of HR: 0.45-0.97; = 0.02) upon multivariate Cox regression analysis. Correspondingly, interleukin 10 (IL10), a cytokine released by cytotoxic T-cells, was likewise significantly elevated in T-lymphocytes of non-relapse GCC patients (HR: 0.3; 95% CI of HR: 0.14-0.65; = 0.002). Our data indicate that glycosylation and activation of T-lymphocytes may play a pivotal role in disease control in GCC patients with primary progressive or relapsed disease

Do Associations Support Authoritarian Rule? Tentative Answers from Algeria, Mozambique, and Vietnam

Whether associations help to democratise authoritarian rule or support those in power is a contested issue that so far lacks a cross-regional perspective. Drawing on relational sociology, this paper explores the impact of state power in Algeria, Mozambique, and Vietnam on associations and vice versa. We focus on decision-making in associations and on three policy areas - welfare policy concerning HIV/AIDS, economic policy concerning small and mediumsized enterprises, policies concerning gender equality and the rights of women and sexual minorities - to assess the relations between associations and the state's infrastructural and discursive power. Most associations interviewed by us in the three countries accept or do not openly reject the state's and/or the state ruling party's various forms of interference in internal decision-making processes. Whereas associations in Algeria and Vietnam help to maintain the state's control through welfare provision, associations in Mozambique can weaken this form of infrastructural state power. Moreover, business and professionals' associations in all three countries help maintain the state's control through limited participation, i.e. another form of infrastructural state power. Finally, associations in all three countries support the state's discourse and policies in the area of gender equality and women's rights, though in all three countries at least some NGOs help weaken this form of state power