The effect of bolus advisors on glycaemic parameters in adults with diabetes on intensive insulin therapy: A systematic review with meta-analysis.

AIM: To conduct a systematic review with meta-analysis to provide a comprehensive synthesis of randomized controlled trials (RCTs) and prospective cohort studies investigating the effects of currently available bolus advisors on glycaemic parameters in adults with diabetes. MATERIALS AND METHODS: An electronic search of PubMed, Embase, CINAHL, Cochrane Library and ClinicalTrials.gov was conducted in December 2022. The risk of bias was assessed using the revised Cochrane Risk of Bias tool. (Standardized) mean difference (MD) was selected to determine the difference in continuous outcomes between the groups. A random-effects model meta-analysis and meta-regression were performed. This systematic review was registered on PROSPERO (CRD42022374588). RESULTS: A total of 18 RCTs involving 1645 adults (50% females) with a median glycated haemoglobin (HbA1c) concentration of 8.45% (7.95%-9.30%) were included. The majority of participants had type 1 diabetes (N = 1510, 92%) and were on multiple daily injections (N = 1173, 71%). Twelve of the 18 trials had low risk of bias. The meta-analysis of 10 studies with available data on HbA1c showed that the use of a bolus advisor modestly reduced HbA1c compared to standard treatment (MD -011%, 95% confidence interval -0.22 to -0.01; I2 = 0%). This effect was accompanied by small improvements in low blood glucose index and treatment satisfaction, but not with reductions in hypoglycaemic events or changes in other secondary outcomes. CONCLUSION: Use of a bolus advisor is associated with slightly better glucose control and treatment satisfaction in people with diabetes on intensive insulin treatment. Future studies should investigate whether personalizing bolus advisors using artificial intelligence technology can enhance these effects.

Taxonomy of teaching methods and their use in health professions education: a scoping review protocol.

INTRODUCTION: Applying the lens of social constructivist theory, teaching methods facilitate the process of learning and may be used differently across settings to align learning goals. Teaching methods are used across disciplines, occupations and learning settings, yet terminology, descriptions and application for use vary widely. This scoping review will identify eligible literature of reported teaching methods with documented descriptions across disciplines with a focus of how teaching methods are applied to health professions education. A literary description of a teaching method was used as a basis from which to select eligible articles based on two criteria, a specified method and delivery of that teaching by a teacher figure. METHODS AND ANALYSIS: Using the extension of the Joanna Briggs Institute methodology aligned to Arksey and O'Malley's six-stage framework and the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews guidelines, this scoping review will systematically search ERIC, Embase, Web of Science and PubMed databases. The search strategy was supported by an information specialist. Eligible studies will be identified in a two-stage screening process with four researchers. To complement eligible peer-reviewed literature, we will also search out relevant grey literature including University Websites, Conference Programmes and handsearched reference lists. Data extraction will be performed using a developed data extraction tool. A narrative summary will accompany charted results and describe the results aligned to the study objectives. ETHICS AND DISSEMINATION: As no intervention or patient recruitment is required for this research, ethics board approval is not required. Results will be disseminated via publication in a peer-reviewed journal, conference presentations and where feasible reaching out to those organisations and universities with published glossaries of terms for teaching.

Social competence improves the performance of biomimetic robots leading live fish.

Collective motion is commonly modeled with static interaction rules between agents. Substantial empirical evidence indicates, however, that animals may adapt their interaction rules depending on a variety of factors and social contexts. Here, we hypothesized that leadership performance is linked to the leader's responsiveness to the follower's actions and we predicted that a leader is followed longer if it adapts to the follower's avoidance movements. We tested this prediction with live guppies that interacted with a biomimetic robotic fish programmed to act as a 'socially competent' leader. Fish that were avoiding the robot were approached more carefully in future approaches. In two separate experiments we then asked how the leadership performance of the socially competent robot leader differed to that of a robot leader that either approached all fish in the same, non-responsive, way or one that did change its approach behavior randomly, irrespective of the fish's actions. We found that (1) behavioral variability itself appears attractive and that socially competent robots are better leaders which (2) require fewer approach attempts to (3) elicit longer average following behavior than non-competent agents. This work provides evidence that social responsiveness to avoidance reactions plays a role in the social dynamics of guppies. We showcase how social responsiveness can be modeled and tested directly embedded in a living animal model using adaptive, interactive robots.

Intraperitoneal drug delivery systems releasing cytostatic agents to target gastro-intestinal peritoneal metastases in laboratory animals: a systematic review.

For peritoneal metastases (PM), there are few curative treatment options, and they are only available for a select patient group. Recently, new therapies have been developed to deliver intraperitoneal chemotherapy for a prolonged period, suitable for a larger patient group. These drug delivery systems (DDSs) seem promising in the experimental setting. Many types of DDSs have been explored in a variety of animal models, using different cytostatics. This review aimed to provide an overview of animal studies using DDSs containing cytostatics for the treatment of gastro-intestinal PM and identify the most promising therapeutic combinations. The review was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines and Systematic Review Center for Laboratory Animal Experimentation (SYRCLE) guidelines. The 35 studies included revealed similar results: using a cytostatic-loaded DDS to treat PM resulted in a higher median survival time (MST) and a lower intraperitoneal tumor load compared to no treatment or treatment with a 'free' cytostatic or an unloaded DDS. In 65% of the studies, the MST was significantly longer and in 24% the tumor load was significantly lower in the animals treated with cytostatic-loaded DDS. The large variety of experimental setups made it impossible to identify the most promising DDS-cytostatic combination. In most studies, the risk of bias was unclear due to poor reporting. Future studies should focus more on improving the clinical relevance of the experiments, standardizing the experimental study setup, and improving their methodological quality and reporting.

Temporal trends of sex differences for COVID-19 infection, hospitalisation, severe disease, intensive care unit (ICU) admission and death: a meta-analysis of 229 studies covering over 10M patients.

Background: This review aims to investigate the association of sex with the risk of multiple COVID-19 health outcomes, ranging from infection to death. Methods: Pubmed and Embase were searched through September 2020. We considered studies reporting sex and coronavirus disease 2019 (COVID-19) outcomes. Qualitative and quantitative data were extracted using standardised electronic data extraction forms with the assessment of Newcastle Ottawa Scale for risk of bias. Pooled trends in infection, hospitalization, severity, intensive care unit (ICU) admission and death rate were calculated separately for men and women and subsequently random-effects meta-analyses on relative risks (RR) for sex was performed. Results: Of 10,160 titles, 229 studies comprising 10,417,452 patients were included in the analyses. Methodological quality of the included studies was high (6.9 out of 9). Men had a higher risk for infection with COVID-19 than women (RR = 1.14, 95%CI: 1.07 to 1.21). When infected, they also had a higher risk for hospitalization (RR = 1.33, 95%CI: 1.27 to 1.41), higher risk for severe COVID-19 (RR = 1.22, 95%CI: 1.17 to 1.27), higher need for Intensive Care (RR = 1.41, 95%CI: 1.28 to 1.55), and higher risk of death (RR = 1.35, 95%CI: 1.28 to 1.43). Within the period studied, the RR for infection and severity increased for men compared to women, while the RR for mortality decreased for men compared to women. Conclusions: Meta-analyses on 229 studies comprising over 10 million patients showed that men have a higher risk for COVID-19 infection, hospitalization, disease severity, ICU admission and death. The relative risks of infection, disease severity and death for men versus women showed temporal trends with lower relative risks for infection and severity of disease and higher relative risk for death at the beginning of the pandemic compared to the end of our inclusion period. PROSPERO registration: CRD42020180085 (20/04/2020).

Sedentary behaviour, physical activity and cardiometabolic health in highly trained athletes: A systematic review and meta-analysis.

Prolonged periods of sedentary time appear to increase the risk for the development of several chronic conditions and all-cause mortality, even when moderate-to-vigorous physical activity (MVPA) is taken into consideration. However, whether the beneficial health effects of MVPA in highly active individuals remain present when leisure time is spent sedentary remains speculative. Therefore, we systematically evaluated off-training sedentary behaviour and physical activity levels in athletes. Studies were collected from four bibliographic databases (PubMed, Embase, Web of Science and The Cochrane Central Register of Controlled Trials). Studies were eligible for inclusion if they evaluated sedentary behaviour and physical activity levels among athletes. Data from athletes were compared with the general population and pooled using a random-effects model. After deduplication 3104 were identified of which 13 studies met inclusion criteria. Compared to the general population, athletes spent significantly more time in sedentary behaviour (+79 min/day; 95% confidence interval [CI]: [41, 65] min/day; p<0.001). In addition, athlete individuals spent less time in light intensity physical activity (-92 min/day; 95% CI: [-117, -66] min/day; p<0.001) and had increased levels of MVPA (+62 min/day; 95% CI: [38, 85] min/day; p<0.001) compared to the general population. Athletes exceed the average time spend sedentary per day and make them even more sedentary compared to the general population.

Deep-time climate legacies affect origination rates of marine genera.

Biodiversity dynamics are shaped by a complex interplay between current conditions and historic legacy. The interaction of short- and long-term climate change may mask the true relationship of evolutionary responses to climate change if not specifically accounted for. These paleoclimate interactions have been demonstrated for extinction risk and biodiversity change, but their importance for origination dynamics remains untested. Here, we show that origination probability in marine fossil genera is strongly affected by paleoclimate interactions. Overall, origination probability increases by 27.8% [95% CI (27.4%, 28.3%)] when a short-term cooling adds to a long-term cooling trend. This large effect is consistent through time and all studied groups. The mechanisms of the detected effect might be manifold but are likely connected to increased allopatric speciation with eustatic sea level drop caused by sustained global cooling. We tested this potential mechanism through which paleoclimate interactions can act on origination rates by additionally examining a proxy for habitat fragmentation. This proxy, continental fragmentation, has a similar effect on origination rates as paleoclimate interactions, supporting the importance of allopatric speciation through habitat fragmentation in the deep-time fossil record. The identified complex nature of paleoclimate interactions might explain contradictory conclusions on the relationship between temperature and origination in the previous literature. Our results highlight the need to account for complex interactions in evolutionary studies both between and among biotic and abiotic factors.

Extinction risk controlled by interaction of long-term and short-term climate change.

Assessing extinction risk from climate drivers is a major goal of conservation science. Few studies, however, include a long-term perspective of climate change. Without explicit integration, such long-term temperature trends and their interactions with short-term climate change may be so dominant that they blur or even reverse the apparent direct relationship between climate change and extinction. Here we evaluate how observed genus-level extinctions of arthropods, bivalves, cnidarians, echinoderms, foraminifera, gastropods, mammals and reptiles in the geological past can be predicted from the interaction of long-term temperature trends with short-term climate change. We compare synergistic palaeoclimate interaction (a short-term change on top of a long-term trend in the same direction) to antagonistic palaeoclimate interaction such as long-term cooling followed by short-term warming. Synergistic palaeoclimate interaction increases extinction risk by up to 40%. The memory of palaeoclimate interaction including the climate history experienced by ancestral lineages can be up to 60 Myr long. The effect size of palaeoclimate interaction is similar to other key factors such as geographic range, abundance or clade membership. Insights arising from this previously unknown driver of extinction risk might attenuate recent predictions of climate-change-induced biodiversity loss.

Demographic risk factors for COVID-19 infection, severity, ICU admission and death: a meta-analysis of 59 studies.

OBJECTIVE: We aimed to describe the associations of age and sex with the risk of COVID-19 in different severity stages ranging from infection to death. DESIGN: Systematic review and meta-analysis. DATA SOURCES: PubMed and Embase through 4 May 2020. STUDY SELECTION: We considered cohort and case-control studies that evaluated differences in age and sex on the risk of COVID-19 infection, disease severity, intensive care unit (ICU) admission and death. DATA EXTRACTION AND SYNTHESIS: We screened and included studies using standardised electronic data extraction forms and we pooled data from published studies and data acquired by contacting authors using random effects meta-analysis. We assessed the risk of bias using the Newcastle-Ottawa Scale. RESULTS: We screened 11.550 titles and included 59 studies comprising 36.470 patients in the analyses. The methodological quality of the included papers was high (8.2 out of 9). Men had a higher risk for infection with COVID-19 than women (relative risk (RR) 1.08, 95% CI 1.03 to 1.12). When infected, they also had a higher risk for severe COVID-19 disease (RR 1.18, 95% CI 1.10 to 1.27), a higher need for intensive care (RR 1.38, 95% CI 1.09 to 1.74) and a higher risk of death (RR 1.50, 95% CI 1.18 to 1.91). The analyses also showed that patients aged 70 years and above have a higher infection risk (RR 1.65, 95% CI 1.50 to 1.81), a higher risk for severe COVID-19 disease (RR 2.05, 95% CI 1.27 to 3.32), a higher need for intensive care (RR 2.70, 95% CI 1.59 to 4.60) and a higher risk of death once infected (RR 3.61, 95% CI 2.70 to 4.84) compared with patients younger than 70 years. CONCLUSIONS: Meta-analyses on 59 studies comprising 36.470 patients showed that men and patients aged 70 and above have a higher risk for COVID-19 infection, severe disease, ICU admission and death. PROSPERO REGISTRATION NUMBER: CRD42020180085.

Can consumer wearable activity tracker-based interventions improve physical activity and cardiometabolic health in patients with chronic diseases? A systematic review and meta-analysis of randomised controlled trials.

BACKGROUND: To date, it is unclear if consumer wearable activity trackers (CWATs), with or without behaviour multi-component strategies, effectively improve adherence to physical activity and health outcomes under free living conditions in populations with chronic diseases. Therefore, we systematically evaluated the efficacy of CWAT-based interventions to promote physical activity levels and cardiometabolic health in populations with chronic diseases. METHODS: Randomised controlled trials were collected from five bibliographic databases (PubMed, Embase, Web of Science, The Cochrane Central Register of Controlled Trials and CINAHL). Studies were eligible for inclusion if they evaluated a CWAT-based counselling intervention versus control intervention among patients with chronic respiratory diseases, type 2 diabetes mellitus, cardiovascular diseases, overweight/obesity, cognitive disorders, or sedentary older adults. Data were pooled using a random-effects model. RESULTS: After deduplication 8147 were identified of which 35 studies met inclusion criteria (chronic respiratory diseases: 7, type 2 diabetes mellitus: 12, cardiovascular diseases: 6, overweight/obesity: 3, cognitive disorders: 1, sedentary older adults: 6). Compared to control groups, CWAT-based interventions significantly increased physical activity by 2123 steps per day (95% confidence interval [CI], [1605-2641]; p < 0.001). In addition, CWAT-based interventions in these populations significantly decreased systolic blood pressure (- 3.79 mm Hg; 95% CI: [- 4.53, - 3.04] mm Hg; p < 0.001), waist circumference (- 0.99 cm; 95% CI: [- 1.48, - 0.50] cm; p < 0.001) and low-density lipoprotein cholesterol concentration (- 5.70 mg/dl; 95% CI: [- 9.24, - 2.15] mg/dl; p = 0.002). CONCLUSION: CWAT-based interventions increase physical activity and have beneficial effects on important health-related outcomes such as systolic blood pressure, waist circumference and LDL cholesterol concentration in patients with chronic diseases.

Challenges of dosimetry of ultra-short pulsed very high energy electron beams.

Very high energy electrons (VHEE) in the range from 100 to 250MeV have the potential of becoming an alternative modality in radiotherapy because of their improved dosimetric properties compared with 6-20MV photons generated by clinical linear accelerators (LINACs). VHEE beams have characteristics unlike any other beams currently used for radiotherapy: femtosecond to picosecond duration electron bunches, which leads to very high dose per pulse, and energies that exceed that currently used in clinical applications. Dosimetry with conventional online detectors, such as ionization chambers or diodes, is a challenge due to non-negligible ion recombination effects taking place in the sensitive volumes of these detectors. FLUKA and Geant4 Monte Carlo (MC) codes have been employed to study the temporal and spectral evolution of ultrashort VHEE beams in a water phantom. These results are complemented by ion recombination measurements employing an IBA CC04 ionization chamber for a 165MeV VHEE beam. For comparison, ion recombination has also been measured using the same chamber with a conventional 20MeV electron beam. This work demonstrates that the IBA CC04 ionization chamber exhibits significant ion recombination and is therefore not suitable for dosimetry of ultrashort pulsed VHEE beams applying conventional correction factors. Further study is required to investigate the applicability of ion chambers in VHEE dosimetry.

Recurrent fetal complex ovarian cysts with rupture followed by simple cyst in the neonatal period with no adverse sequelae.

Fetal ovarian cysts are the most frequent type of abdominal tumors in female fetuses with prenatal detection rate of more than 30%. The etiology of fetal ovarian cysts is unclear, but hormonal stimulation as well as presence of maternal diabetes, hypothyroidism, Rh iso-immune hemolytic disease and toxemia has been generally considered responsible for the disease. Complications of fetal ovarian cysts include compression of other viscera, cyst rupture, hemorrhage and, most frequently, ovarian torsion with consequent loss of the ovary. Management is controversial with several options described in the literature, including watchful expectancy, antenatal aspiration of simple cysts to prevent torsion and ovarian loss and finally, resection of all complex cysts in the neonatal period. To date, no case report has described recurrent complex cysts with rupture in the fetal period and recurrence of simple cyst in neonatal period. By presenting this case, we wanted to show that surgical intervention in case of prenatally diagnosed fetal ovarian cyst should be considered postnatally and only in symptomatic or complicated cases.

Dewatering behavior of sewage screenings.

Screenings from municipal sewage treatment plants have increased in importance in recent years, particularly in Germany, where laws prohibit depositing of screenings in landfill. This paper presents basic investigations of sewage screenings, especially the structure and dewatering behavior. Two standard experiments are conducted. First, the relationship between pressure and water content is determined. Secondly the flow resistance as a function of pressure is evaluated. The results help to derive simulation models in order to understand how the material behaves inside a wash press.

Monthly itraconazole versus classic homeopathy for the treatment of recurrent vulvovaginal candidiasis: a randomised trial.

OBJECTIVE: Antimycotics effectively treat sporadic and recurrent vulvovaginal candidiasis (RVVC). Classic homeopathy (CH) is also used to treat this condition. We compared the efficacy of CH and itraconazole in reducing the frequency of RVVC episodes. DESIGN: Single-centre, prospective, randomised trial. SAMPLE: One hundred-and-fifty patients with a history of RVVC and an acute episode of VVC. METHODS: Women were randomised into 3 groups: itraconazole with lactobacilli (group 1), itraconazole without lactobacilli (group 2) and CH (group 3). Itraconazole treatment of acute infection was followed by a 6-month maintenance regimen with monthly single-day itraconazole (200 mg bid). Women in group 1 were given additional vaginal lactobacilli for 6 days per month throughout the maintenance regimen Thereafter, patients were followed without treatment for 6 months. CH treatment was performed for 12 months. RESULTS: Women in groups 1 and 2 reached a culture-free status significantly earlier than women in group 3 (log-rank test; P < 0.0001). Specifically, before the start of the maintenance regimen, 44 of 49 women (89.8%) in group 1 and 40 of 47 women (85%) in group 2 were free of Candida detectable by culture, 22 of 46 (47%) women in group 3 reached a culture-free status after the first visit, but had a recurrence significantly earlier compared with women in groups 1 and 2 (log-rank test; P = 0.002). After 12 months, 19 of 25 (76%) women in group 1, 18 of 23 (78%) women in group 2 and 9 of 23 (39%) women in group 3 were free of culture-detectable Candida. Assessment of RVVC-associated complaints by VAS score showed that women in group 3 had a significantly higher level of discomfort (36.8, 25.1 and 27.7 respectively; P < 0.001) and were significantly less satisfied (59.2, 68.2 and 71.7 respectively; P < 0.001) than patients in groups 1 and 2. CONCLUSIONS: Monthly cycle-dependent itraconazole is more effective than CH in the treatment of RVVC. Lactobacilli do not confer an added benefit.

Generation of ultrafast terahertz radiation pulses on metallic nanostructured surfaces.

A resonant "incoherent" rectification process is presented relying on the excitation of surface plasmons on a nanostructured metal surface. Excitation of gold and silver films with 800-nm femtosecond laser pulses results in the emission of terahertz radiation with an angle-dependent efficiency and an approximately third-order power dependence. It is shown that the source of this terahertz pulse generation is the surface-plasmon-assisted multiphoton ionization and ponderomotive acceleration in the evanescent field of the surface plasmon. Simple models are used to understand the forces and dynamics near the surface.

200 ns pulse high-voltage supply for terahertz field emission.

We present a method of generating 200 ns high-voltage (up to 40 kV) pulses operating at repetition rates of up to 100 kHz, which may be synchronized with laser pulses. These supplies are simple to make and were developed for ultrafast terahertz pulse generation from GaAs photoconductive antennas using a high-repetition-rate regeneratively amplified laser. We also show an improvement in signal-to-noise ratio over a continuous dc bias field and application of the supply to terahertz pulse generation.

Terahertz-pulse emission through laser excitation of surface plasmons in a metal grating.

The second-order processes of optical-rectification and photoconduction are well known and widely used to produce ultrafast electromagnetic pulses in the terahertz frequency domain. We present a new form of rectification that relies on the excitation of surface plasmons in metal films deposited on a shallow grating. Multiphoton ionization and ponderomotive acceleration of electrons in the enhanced evanescent field of the surface plasmons results in a femtosecond current surge and emission of terahertz electromagnetic radiation. Using gold, this rectification process is third or higher-order in the incident field.

The detection of HPV DNA improves the recognition of cervical intraepithelial lesions.

UNLABELLED: Reasons that influence the efficacy of cervical cancer screening are failure to screen all women at risk, as well as inherent technical limitations of the conventional cervical smear. HPV DNA testing is a supplementary, objective test less independent on sampling failure. The aim of this study was to compare results of HPV DNA screening to cytological smears (CS) and histological diagnosis. From January 1995 to January 1999, cytological smears, cells for HPV DNA analysis and cervical biopsies were obtained from 280 women included in this study. STATISTICAL METHODS: Fisher's exact test (2x2 contingency tables, P<0.01), Pearson Chi-square, P< 0.05, Spearman's rank correlation R. Sixty patients (21.4%) tested positive for low-risk (LR-HPV), 227 (81.1%) positive for high-risk HPV (HR-HPV). The CS proved to be a strong predictor for the histological diagnosis, reaching a sensitivity of 93.4%, a specificity of 65.8% and a positive predictive value (PPV) of 77.4%. By combining cytology and HPV DNA testing, the sensitivity could be considerably enhanced (99.0%), though at a price of loss in specificity (30.1%). HPV DNA testing, available as a commercially standardized product, leads to a significant rise in sensitivity when used as an additional diagnostic tool to cytological screening methods and thus contributes to reduce the incidence of cervical carcinomas.

Port site metastases after laparoscopic lymph node staging of cervical carcinoma.

The literature revealed only six cases of cervical carcinoma metastatic to a port site after laparoscopic lymphadenectomy. A woman with a poorly differentiated squamous cell carcinoma of the cervix had port site metastases after laparoscopic lymph node staging. The frequency of this event might be higher than expected. Therefore, surgeons should reduce mechanical irritation of port sites and spillage of tumor cells.