Consecutive Trial Research Articles

Comparative study of two different horizontal stabilisation methods in arthroscopically assisted coracoclavicular stabilisation for acute acromioclavicular joint dislocations-Good clinical outcome and no correlation to recurrent anteroposterior instability.

The hypothesis of this study was that acromioclavicular K-wire transfixation is noninferior to horizontal FiberTape cerclage in terms of vertical and horizontal stability in the short follow-up period of acute acromioclavicular joint (ACJ) dislocations fixed with an arthroscopically assisted coracoclavicular single bundle endobutton cerclage system. The secondary aim was to investigate the impact of postoperative recurrent instability on clinical outcomes in these populations. In this consecutive clinical trial, all patients who underwent surgery for acute AC joint dislocation between January 2017 and December 2021 were included. Two groups were formed according to the additional AC stabilisation technique (K-wire group, cerclage group). Clinical examination and bilateral radiologic analysis (Zanca stress view, Alexander view) were performed with a follow-up period of at least 12 months. Satisfaction, return to sports, active range of motion, global shoulder scores and specific shoulder scores including constant score, disabilities of the arm, shoulder and hand (DASH) score and ACJ instability score (ACJI) were evaluated. Complications, including recurrent instability, and revision rate were assessed. Included were 59 patients (32 K-wire group, 27 cerclage group, 92% male, median follow-up 33 months). No significant differences were found in the clinical outcome parameters between the different techniques, except for the DASH value (superior in the K-wire group). Recurrent anteroposterior instability was radiographically detected in 27% of patients. No correlation was found between anteroposterior instability and clinical outcome parameters. There was no revision surgery due to chronic ACJ instability. Horizontal ACJ stabilisation with temporary K-wire transfixation does not appear to be inferior to a FiberTape cerclage technique in acute ACJ dislocations stabilised in an arthroscopically assisted single bundle DogBone technique. Recurrent ACJ instability detected radiographically does not necessarily correlate with the functional outcome and can be well compensated. Level III.

Abstract 4171: Utilizing biopsy-free virtual histology for improved clinical efficiency in the dermatologic surgical setting

Abstract The ability to accurately define tumor margins may enhance tissue sparing and increase efficiency in the dermatologic surgery process, but no device exists that serves this role. Reflectance Confocal Microscopy (RCM) provides non-invasive cellular resolution of the skin. The only clinically-approved RCM device is bulky, non-portable, and requires a tissue cap which makes mapping of the underlying tissue impossible. We recently combined “virtual histology”, a machine learning algorithm with RCM images from this standard RCM device to generate biopsy-free histology to overcome these limitations. Whether virtual histology can be used with a portable, handheld RCM device to scan for residual tumor and tumor margins is currently unknown. We hypothesize that combining a handheld RCM device with virtual histology could provide accurate tumor margin assessment. We determined whether our established virtual histology algorithm could be applied to images from a portable RCM device and whether these pseudo-stained virtual histology images correlated with histology from skin specimens. The study was conducted as a prospective, consecutive non-randomized trial at a Veterans Affairs Medical Center dermatologic surgery clinic. All patients greater than 18 years of age with previously biopsied BCC, SCC, or SCCis were included. Successive confocal images from the epidermis to the dermis were obtained 1.5 microns apart from the handheld RCM device to detect residual skin cancer. The handheld, in-vivo RCM images were processed through a conditional generative adversarial network-based machine learning algorithm to digitally convert the images into H&E pseudo-stained virtual histology images. Virtual histology of in-vivo RCM images from unbiopsied skin captured with the portable RCM device were similar to those obtained with the standard RCM device and virtual histology applied to portable RCM images correctly correlated with frozen section histology. Residual tumors detected with virtual histology generated from the portable RCM images accurately corresponded with residual tumors shown in the frozen surgical tissue specimen. Residual tumor was also not detected when excised tissue was clear of tumor following surgical procedure. Thus, the combination of virtual histology with portable RCM may provide accurate histology-quality data for evaluation of residual skin cancer prior to surgery. Combining machine learning-based virtual histology with handheld RCM images demonstrates promise in providing insights into tumor characteristics and has the potential to assist the surgeon and better guide practice decisions to more efficiently serve patients, leading to decreased layers and appointment times. Future work is needed to provide real time virtual histology, convert horizontal/confocal sections into vertical or 3D sections, and to perform clinical studies to map tumors in tissue. Citation Format: Rachel Wahhab, Nelly Kokikian, Jingxi Li, Jason Garfinkel, Stephanie Martin, David Beynet, Aydogan Ozcan, Philip Scumpia. Utilizing biopsy-free virtual histology for improved clinical efficiency in the dermatologic surgical setting [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 4171.

Third-Generation Transcatheter Aortic Heart Valve with Reverse Parachute Sealing Cuff in Patients with Aortic Valve Disease

The Navitor (Abbott Inc, IL, USA) transcatheter heart valve is a novel third-generation self-expanding bioprosthesis with specific features to mitigate paravalvular regurgitation (PVR). Owing to its novelty, there is a paucity of data on its application in clinical practice. Consecutive cohort analysis of the use of the Navitor system in an as-treated clinical setting at a quaternary heart hospital. Sixty consecutive non-clinical trial patients treated with Navitor were identified. All patients underwent a successful procedure. The mean age was 79.3 years (±SD 7.82), 56.67% (n=34) were female, and the mean STS score was 4.87 (±SD 5.70). At 30 days post-procedure, all patients were alive with no readmissions for heart failure. One patient had a major vascular complication (1.7%). Four patients (7.14% of patients without a pre-existing pacemaker) received a new permanent pacemaker. Two patients (3.4%) had a non-disabling stroke. PVR at 30 days was trivial or none in 75% of patients, and no patient had worse than mild PVR. The Navitor system in this as-treated cohort was associated with favourable clinical, haemodynamic, and safety outcomes.

Straw strip mulch improves soil moisture similar to plastic film mulch but with a higher net income

Soil surface mulch is an important measure for conserving more moisture and increasing yield in rainfed agroecosystems. Straw strip mulch (SM) is a new mulching technique for clean production, but the regulation mechanisms of SM on soil moisture and potato yield formation is lack of systematic understanding yet. Therefore, a five-year (2018–2022) consecutive field trial on potato (Solanum tuberosum L.) was conducted in the semiarid rainfed region of Northwest China, using three treatments: full-field black plastic film mulch (PM), SM with 42% of the field area mulched using whole corn stalks, and no mulch as the control (NM). Relative to NM, on average across five growing seasons of potato, SM increased (P < 0.05) the soil moisture in 0–200 cm depth by 6.6%, fresh tuber yield ha−1 by 15.0%, dry tuber yield ha−1 by 23.6%, weight per tuber by 13.3%, net income by 26.3% (8268 ¥ ha−1), and output / input ratio by 10.5%, biomass by 16.5%, water use efficiency 28.5%, but reduced the total water consumption (ET) throughout the potato growth period by 12.9 mm. SM had a similar (P > 0.05) soil moisture in 0–200 cm depth, the total ET, the dry tuber yield and WUE as PM but with a 10.7% (2455 ¥ ha−1) higher net income. Mulching practices not only increased the soil moisture at different growth stages, but also regulated its utilization. Compared with NM, the maximum increase of soil moisture in SM and PM occurred at tuber formation stage. SM and PM decreased water consumptions in early period (sowing to tuber formation) and late period (tuber bulking to maturity), as well as their ratios to total ET, but increased them in middle period (tuber formation to tuber bulking). The increased weight per tuber was the primary yield component that leads to the increased yield in SM and PM. It was concluded that mulching practices improve soil moisture by inhibiting evaporation, increase transpiration ratio to ET, reduce water consumption of early period and its ratio to total ET while increasing them of middle period, resulting in significant increases in biomass and weight per tuber, which were the main mechanisms for yield increases in SM and PM compared to NM. SM is suitable to be popularized in a semiarid rainfed agroecosystem for potato production as an alternative to PM.

Manual dexterity in school-age children measured by the Grooved Pegboard test: Evaluation of training effect and performance in dual-task

BackgroundManual dexterity is the ability to manipulate objects using the hands and fingers for a specific task. Although manual dexterity is widely investigated in the general and special population at all ages, numerous aspects still remain to be explored in children. The aim of this study was to assess the presence of the training effect of the execution of the Grooved Pegboard test (GPT) and to measure the performance of the GPT in dual-task (DT), i.e., during a motor task and a cognitive task. MethodsIn this observational, cross-sectional study manual dexterity was assessed in children aged between 6 and 8. The procedure consisted of two phases: (1) the execution of five consecutive trials of the GPT to evaluate the training effect; (2) the execution of one trial of the GPT associated with a motor task (finger tapping test, GPT-FTT), and one trial of the GPT associated with a cognitive task (counting test, GPT-CT) to evaluate the performance in DT. ResultsAs for the training effect, a significant difference (p < 0.001) between the five trials of the GPT (i.e., GPT1, GPT2, GPT3, GPT4, GPT5) was detected. In particular, we found a significant difference between GPT1 and GPT3 (p < 0.05), GPT1 and GPT4 (p < 0.001), and GPT1 and GPT5 (p < 0.001), as well as between GPT2 and GPT4 (p < 0.001), and GPT2 and GPT5 (p < 0.001).As for the performance in DT, no differences between the best trial of the GPT (i.e., GPT5) and both the GPT-FTT and GPT-CT was found. ConclusionOur findings suggest that the execution of the GPT in children has a training effect up to the third consecutive trial. Furthermore, the administration of the GPT in DT does not affect GPT performance.

Fault-tolerant design of non-linear iterative learning control using neural networks

The design of neural-network-based iterative learning control for non-linear systems is addressed in the setting of a fault tolerant control regime. Taking advantage of the repetitive character of the control task, the inherent uncertainty related to a potential faulty system state can be properly accommodated in terms of a data-driven iterative learning scheme with neural networks used for forward/inverse modeling as well as for controller synthesis. The resulting control technique is supposed to be flexible enough to accurately compensate the faults occurring on both the sensors and actuators and, additionally, take into account the disturbances and noise acting on the system. A complete characterization of the novel fault-tolerant iterative learning scheme is provided including system identification, fault detection and accommodation. Also, the painstaking convergence analysis is presented and the resulting sufficient conditions can be constructively used to determine the update of control law in the consecutive process trial. The excellent performance of the developed control scheme is illustrated by a nontrivial example of tracking control for a magnetic brake system on various scenarios involving actuator and/or sensor faults.

Autumn Film Mulched Ridge Microfurrow Planting Improves Yield and Nutrient-Use Efficiency of Potatoes in Dryland Farming

Potatoes (Solanum tuberosum) are the most important noncereal crop in the world. Increasing potato production is critical for future global food security. China is the world’s largest potato producer, and potato productivity is constrained by water scarcity and poor fertilizer use efficiency (NUEF). Recently, autumn film mulched ridge microfurrow rainwater harvesting (ARF) tillage has been successfully applied in potato production in dryland farming in Northwest China. However, the effects of ARF on the use efficiency (NUEF) of applied nitrogen (N), phosphorus (P), and potassium (K) nutrients in potatoes have not been systematically studied. A 3-year, consecutive field trial with four treatments, including moldboard planting without fertilizer application (control, CK), spring and autumn film mulched ridge microfurrow rainwater harvesting planting (SRF and ARF), and standard film mulched ridge-furrow planting (FRF), was conducted during 2018–2020. ARF greatly increased the water levels in the 0–200 cm soil profile at potato harvest compared to SRF, FRF, and CK. ARF and SRF significantly increased the levels of soil organic carbon (SOC), total and available NPK (TN, TP, TK and AN, AP, AK) compared to FRF and CK, with ARF being the most efficient at increasing the levels of the AN, AP, and AK. ARF significantly improved the soil water and nutrient activity and contributed the most to potato tuber and biomass yield and hence the NUEF. Under ARF, significant and positive associations were observed between the soil fertility traits, soil water storage (SWS), potato tuber yield, biomass yield, and NUEF. Soil fertility traits and the SWS were positively correlated with potato tuber and biomass yield. The SWS, potato tuber, and biomass yield positively correlated with the partial factor productivity (PFP) and the recovery efficiency (RE) of the applied NPK nutrients. Increased nutrient levels and their combination increased the NUEF and NUEF’s components. The TN and AN contributed more significantly to the PEP and agronomic efficiency (AE) of the applied NPK nutrients; the TP was significantly positively correlated with the AE (AEN, AEP, and AEK), while the AP was correlated with PEP (PFPN, PFPP, and PFPK) and RE (REN, REP, and REK); the TK was significantly positively correlated with the PFP and RE of the applied PK nutrients, while the AK was significantly positively correlated with the PEP, AE, and RE of the applied K nutrients. Therefore, ARF results in a synchronous increase in yield and NUEF and is the most efficient planting system for potato production in dryland farming.

Response to electroconvulsive therapy in treatment-resistant depression: nationwide observational follow-up study.

Previous studies have not investigated response rates after electroconvulsive therapy (ECT) in patients with non-psychotic treatment-resistant depression (TRD). To assess and compare the response rate of ECT for patients with TRD and non-TRD, in a large and clinically representative patient sample. Patients aged ≥18 years, who were treated for a unipolar, non-psychotic depressive episode with at least one ECT session as part of a first-time, index ECT series between 1 January 2011 and 31 December 2017 were included from the Swedish National Quality Register for ECT. Patients who had initiated a third consecutive trial of antidepressants or add-on medications before start of ECT were classified as having TRD. Patients not meeting criteria for TRD were classified as non-TRD. The main outcome was response to ECT according to the Clinical Global Impressions - Improvement Scale (CGI-I), scored as 1 or 2 ('very much' or 'much improved' after ECT, respectively). Logistic regression was used to compare outcome measures between TRD and non-TRD, adjusting for potential confounders. A total of 4244 patients were included. Of these, 1121 patients had TRD and 3123 patients had non-TRD. The CGI-I response rate was 65.9% in the TRD group compared with 75.9% in the non-TRD group (adjusted odds ratio 0.64, 95% CI 0.54-0.75). Older age and more severe depression were predictors of response in patients with TRD. A clear majority of patients with TRD, as well as patients with non-TRD, responded to ECT, although the response rate was somewhat lower for TRD.

Additional Mutational Events at Diagnosis of CML Confer Inferior Failure-Free Survival and Molecular Response for Patients Treated with Frontline Imatinib but Not for Patients Treated with Frontline Second-Generation Tyrosine Kinase Inhibitors

Background We previously performed an integrative genomic analysis for 47 chronic phase (CP)-CML patients at diagnosis who were specifically selected based on optimal or very poor outcome to tyrosine kinase inhibitors (TKIs). Patients who subsequently progressed to blast phase (BP) had a significantly higher frequency of cancer-related gene mutations at diagnosis compared with patients who achieved an optimal response (54% versus 16%). A novel mutational subtype associated with the formation of the Philadelphia (Ph) chromosome, termed Ph-associated rearrangements, were also described and included novel fusions, deletions and inversions adjacent to the BCR::ABL1 junction. These occurred at a higher frequency of patients who progressed to BP compared to those with an optimal response (33% versus 11%). Consequently, we sought to investigate the true incidence and effect of cancer-gene mutations and Ph-associated rearrangements (collectively termed additional mutational events, AMEs) detected at diagnosis and whether outcomes differ based on the TKI initiated. Aim To assess the impact on outcome and molecular response of AMEs detected at diagnosis for patients consecutively treated with imatinib compared to patients treated with second-generation TKIs (2G-TKI). Methods A recently validated hybridization capture sequencing method targeting genes involved in both myeloid and lymphoid malignancies was applied to available diagnostic RNA of consecutive clinical trial patients treated with either frontline imatinib or 2G-TKIs. The 200 imatinib-treated patients (TIDEL II; CML9) were commenced on 600mg daily of imatinib and managed with a highly proactive treatment intervention strategy for suboptimal response, which was either imatinib dose increase or switch to nilotinib. The 2G-TKI patients were enrolled in either DIRECT;CML12 (n=72), where patients commenced dasatinib 100mg daily before dose modification, or either ENESTxtnd or PINNACLE;CML11 (n=44) where patients commenced nilotinib 300mg twice daily. Variants in cancer genes with variant allele frequencies ≥5%, including single nucleotide variants, RNA splice altering variants, small insertions/deletions, gene fusions and focal gene deletions were assessed for pathogenicity using strict criteria. Ph-associated rearrangements were identified. Clinically relevant variants were confirmed as somatic and validated. Kaplan-Meier and cumulative incidence analyses were performed to assess the effect of AMEs on failure-free survival and key molecular outcomes by 36 months. Failure events were as defined by the European LeukemiaNet 2020. Results The incidence of AMEs for imatinib-treated patients was 31% (61/200): 33 (16%) cancer gene mutations and 36 (18%) Ph-associated rearrangements; 8 patients had both subtypes. In the 2G-TKI group, 41 AMEs were identified in 29% (34/116) of patients: 20 (17%) cancer gene mutations and 16 (14%) Ph-associated rearrangements; 2 patients had both subtypes. In total, 14 cancer genes were mutated. Consistent with other studies, ASXL1 mutations were most frequently detected: 18/200 imatinib patients (9%) and 9/116 2G-TKI patients (8%). Using 36-month outcomes as comparison, imatinib-treated patients with AMEs had inferior failure-free survival (84% versus 69%, P=.03), major molecular response (84% versus 72%, P=.02) and MR4 (62% versus 37%, P=.001). In contrast, outcomes in the 2G-TKI cohort were similar irrespective of the presence of AMEs, with regards to failure-free survival (94% versus 91%, P=.47) and achievement of major molecular response (88% versus 83%, P=.71). Interestingly, achievement of MR4 was delayed for patients with AMEs compared to those without AMEs at diagnosis: 51% versus 69%, P=.02 by 24 months; and 63% versus 70%, P=.40 by 36 months. No differences were observed for overall survival or transformation-free survival in either the frontline imatinib or 2G-TKI cohorts. Conclusion These results indicate that while the presence of AMEs do predict for inferior outcomes and molecular responses when patients are treated with frontline imatinib, the more potent 2G-TKIs may overcome the negative impact of the AMEs. The effect for imatinib treated patients was evident despite a starting dose of 600mg and more stringent treatment intervention than currently recommended. This supports a strategy of mutation analysis at diagnosis of CP-CML for optimal TKI selection. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Evaluation of Botanical Soaps for the Management of Pigeonpea Insect Pests

A two year consecutive trial was conducted during kharif 2014-15 and kharif 2015-16 to evaluate neem and pungam soaps @ 10 g l-1 in alone and in combination with indoxacarb (0.5 ml l-1). First spray was given during flowering and second spray was given after fifteen days of the first spray. In both the field trials, neem soap followed by indoxacarb was effective against pigeonpea pod damaging insects followed by pungam soap and indoxacarb. During kharif 2014-15, two sprays of neem soap was on par in efficacy with pungam soap followed by indoxacarb against H. armigera and M. vitrata. When the damage of the pod damaging insects in botanical sprays alone treatments and untreated control was compared, these treatments were effective and good control was achieved. During kharif 2015-16, two sprays of neem soap was on par with NSKE followed by indoxacarb and pungam soap followed by indoxacarb in reducing the damage of H. armigera. In case of M. vitrata, two sprays of neem soap and two sprays of NSKE recorded 50.4 and 44.9% reduction over control and were on par with NSKE followed by indoxacarb in effectiveness. Against plume moth, two sprays of neem soap (4.3% damage) and two sprays of NSKE (5% damage) were on par with pungam soap followed by indoxacarb (4.7% damage).

Evaluation of dendroremediation potential of ten Quercus spp. for heavy metals contaminated soil: A three-year field trial

Woody plants have gained considerable attention for remediating soils contaminated with heavy metals because of their cost-efficient and ecologically friendly nature. However, most studies on potential phytoremediation evaluation are limited to short-term experiments in greenhouse or field, meaning that differences may exist between laboratory results and application in natural environment. In this study, ten Quercus spp. were tested in a consecutive 3-year field trial (2018–2020) to assess their dendroremediation abilities for Cd and Zn contaminated soil. The results revealed that nine Quercus spp. demonstrated good survival ability without any stress, except for Quercus velutina Lam., in the 3-year growth period. In 2020, Quercus texana Buckley and Quercus fabri Hance plants produced the greatest biomass (2100 and 1880 g plant−1) among the nine Quercus spp. Quercus texana had the highest total Cd accumulation (39.3 mg plant−1) in 2020, which was 8.5 times higher than that in 2018, followed by Quercus pagoda Raf. (8.85 mg plant−1) and Q. fabri (8.07 mg plant−1) plants, respectively, whereas Cd accumulation increased by 7.4 times for Q. pagoda and 22 times for Q. fabri compared to 2018. The results from 2020 indicated that Q. fabri had the highest Zn accumulation (205 mg plant−1), followed by Quercus nigra L. (149 mg plant−1) and Q. texana (140 mg plant−1), respectively, and these values increased 14, 6.4, and 6.2 times in comparison to 2018. The comprehensive bioaccumulation index (CBAI) was proposed to evaluate the dendroremediation potential of Quercus spp., suggesting that Q. texana and Q. fabri had the most outstanding potential for remediation of Cd and Zn polluted soil, with the values of 0.82 and 0.60, respectively. In summary, Q. texana and Q. fabri are ideal for remediating Cd/Zn-contaminated soil, and long-term field trials and the CBAI method are helpful for comprehensively evaluating the remediation capacity of trees.

Impact of Polymorphism in the β2-Receptor Gene on Metabolic Responses to Repeated Hypoglycemia in Healthy Humans.

The Arg16 variant in the β2-receptor gene is associated with increased risk of severe hypoglycemia in subjects with type 1 diabetes mellitus. We hypothesized that the Arg16 variant is associated with decreased metabolic and symptomatic responses to recurrent hypoglycemia. Twenty-five healthy male subjects selected according to ADRB2 genotype and being homozygous for either Arg16 (AA; n = 13) or Gly16 (GG; n = 12) participated in 2 consecutive trial days with 3 periods of hypoglycemia (H1-H3) induced by a hyperinsulinemic hypoglycemic clamp. The main outcome measure was mean glucose infusion rate (GIR) during H1-H3. During H1-H3, there was no difference between AA or GG subjects in GIR, counter-regulatory hormones (glucagon, epinephrine, cortisol, growth hormone), or substrate levels of lactate, glycerol, and free fatty acids (FFAs), and no differences in symptom response score or cognitive performance (trail making test, Stroop test). At H3, lactate response was reduced in both genotype groups, but AA subjects had decreased response (mean ± standard error of the mean of area under the curve) of glycerol (-13.1 ± 3.8 μmol L-1 hours; P = .0052), FFA (-30.2 ± 11.1 μmol L-1 hours; P = .021), and β-hydroxybutyrate (-0.008 ± 0.003 mmol L-1 hour; P = .027), while in GG subjects alanine response was increased (negative response values) (-53.9 ± 20.6 μmol L-1 hour; P = .024). There was no difference in GIR between genotype groups, but secondary outcomes suggest a downregulation of the lipolytic and β-hydroxybutyrate responses to recurrent hypoglycemia in AA subjects, in contrast to the responses in GG subjects.

Cattle manure and bio-nourishing royal jelly as alternatives to chemical fertilizers: Potential for sustainable production of organic Hibiscus sabdariffa L.

For sustainable and organic farming, organic manures such as cattle manure (CMn) and bio-nutritious substances such as royal jelly (RJ) should be used as complete or at least partial alternatives to chemical fertilizers (CFs). Therefore, two consecutive trial seasons (2018 and 2019) were conducted to study the effect of soil fertilization with CMn and/or CFs in combination with foliar spraying with RJ on growth, yield, and chemical composition of roselle (Hibiscus sabdariffa L.) plant and seed. The results indicated that spraying roselle plants with RJ resulted in a significant increase in all parameters studied over the control; however, this increase was enhanced when RJ was combined with soil fertilization. The highest values for most of the growth traits, chemical composition of seeds, sepal anthocyanin and vitamin C contents, and sepal acidity were obtained by applying 2 or 4 g RJ L−1 + (30 m3 CMn ha−1 + 50 % dose CFs). In addition, the highest values for yield components and plant chemical composition were obtained by applying 2 or 4 g RJ L−1 + (0 m3 CMn ha−1 + full dose CFs). The results also indicated that applying CMn in combination with RJ gave values mostly close to those of CFs treatment. In conclusion, the results recommend the use of RJ (2 g L−1 as a foliar feeding) along with CMn (30 m3 ha−1) as a partial alternative to chemical fertilizers for sustainably producing healthy roselle sepals.

Excess deaths in treatment-resistant depression.

Background:Patients with treatment-resistant depression (TRD) have an increased mortality risk compared with other patients with depression, but it is not known how this translates into absolute numbers of excess deaths.Methods:Swedish national registers were used to identify a cohort of 118,774 antidepressant initiators 18–69 years old with a depression diagnosis. Patients who initiated a third consecutive treatment trial were classified as having TRD. Flexible parametric survival models were used to estimate the mortality risk due to all causes and external causes (suicides and accidents), comparing TRD patients with patients with other depression while adjusting for clinical and sociodemographic covariates and including interactions with TRD, age, and Charlson comorbidity index (CCI) for a number of somatic comorbidities. Standardized survival was estimated, as were numbers of excess deaths among TRD patients within each age and comorbidity category.Results:Compared with the mortality risk of other depressed patients, patients with TRD experienced excess deaths in most age and comorbidity categories in the range of 7–16 deaths per 1000 patients during 5 years. Highest numbers for all-cause excess deaths were found among patients 18–29 years old with CCI 1, where 16 [95% confidence interval 5–28] of the expected 37 [25–48] deaths per 1000 patients were excess deaths. The majority of the excess deaths were due to external causes.Conclusion:Patients with TRD experience significant numbers of excess deaths compared with other patients with depression.

Roles of the prefrontal cortex in learning to time the onset of pre-existing motor programs

The prefrontal cortex (PFC) is involved in cognitive control of motor activities and timing of future intensions. This study investigated the cognitive control of balance recovery in response to unpredictable gait perturbations and the role of PFC subregions in learning by repetition. Bilateral dorsolateral (DLPFC), ventrolateral (VLPFC), frontopolar (FPFC) and orbitofrontal (OFC) cortex hemodynamic changes induced by unpredictable slips were analyzed as a function of successive trials in ten healthy young adults. Slips were induced by the acceleration of one belt as the participant walked on a split-belt treadmill. A portable functional near-infrared spectroscope monitored PFC activities quantified by oxyhemoglobin (ΔO2Hb) and deoxyhemoglobin (ΔHbR) during the consecutive trial phases: standing, walking, slip-recovery. During the first 3 trials, the average oxyhemoglobin (ΔO2Hbavg) in the DLPFC, VLPFC, FPFC, and OFC cortex was significantly higher during slip-recovery than unperturbed walking or the standing baseline. Then, ΔO2Hbavg decreased progressively from trial-to-trial in the DLPFC, VLPFC, and FPFC, but increased and then remained constant in the OFC. The average deoxyhemoglobin (ΔHbRavg) presented mirror patterns. These changes after the third trial were paralleled by the progressive improvement of recovery revealed by kinematic variables. The results corroborate our previous hypothesis that only timing of the onset of a “good enough recovery motor program” is learned with practice. They also strongly support the assumption that the PFC contributes to the recall of pre-existing motor programs whose onset timing is adjusted by the OFC. Hence, learning is clearly divided into two steps delineated by the switch in activity of the OFC. Additionally, motor processes appear to share the working memory as well as decisional and predictive resources of the cognitive system.

Ammonia mitigation effects from the cow housing and manure storage chain on the nitrogen and carbon footprints of a typical dairy farm system on the North China Plain

Atmospheric ammonia is an important air pollutant, while dairy production is a significant source of ammonia emissions. The aim of the present dairy manure management study was to analyze: 1) the impacts of acidification of the manure surface and/or a vermiculite cover on ammonia, nitrous oxide and methane emissions from animal housing and manure storage stages, 2) the potential influence on the reactive nitrogen (N) and carbon (C) footprints of milk from cradle-to-farm-gate. It was based on a consecutive incubation trial and a life cycle assessment approach for a typical dairy farm system on the North China Plain. Trial results showed that surface-acidification of manure under a slatted floor could reduce ammonia emission by 98 and 22% from housing (one day) and storage stages (38 days), respectively, with small effects on nitrous oxide and methane emissions. The vermiculite cover (storage stage only) reduced ammonia emissions by 98% and methane by 58%, but increased nitrous oxide emissions from storage by almost six times with small absolute losses. The combination of the two mitigations retained 90% of the manure N post-storage relative to that at the start of the housing stage. Life cycle assessment indicated that the reactive-N footprint (NF, i.e. reactive N loss per kg fat- and protein-corrected milk) of milk production was dominated by ammonia emissions and was reduced by 10, 33 and 38% in the manure acidification, manure cover and combination treatments, respectively. Acidification of the manure surface, the vermiculite cover and combination treatments decreased the C footprint (CF, i.e. total greenhouse gas emissions per kg fat- and protein-corrected milk) by 1.0, 1.9 and 2.4%, respectively. This holistic analysis, combining incubation trials and life cycle assessment, indicates that surface-acidification of manure under the slatted floor and a vermiculite cover during manure storage can reduce ammonia emission from a dairy farm system, with an overall positive influence on reduction of NF and CF for dairy farm systems.

The execution of the Grooved Pegboard test in a Dual-Task situation: A pilot study

BackgroundManual dexterity is an important aspect in everyday life, which is widely studied through the Grooved Pegboard Test (GPT). Since Dual-Tasks (DT) activities are widely investigated and important to simulate everyday life situations, the objectives of the present pilot study were the evaluation of the effect of a cognitive task and a motor task during the performance of the GPT and the feasibility of the GPT in a DT contest. A secondary objective was to evaluate the training effect of the GPT. MethodsA total of 31 young adults (20 man and 11 woman, age (SD): 27.7 (2.5)) performed the GPT eight times to understand the presence of a training effect before performing the GPT in DT. The additional tasks were a secondary cognitive task and a secondary motor task. ResultsAll participants were able to complete the required conditions. The GPT performed in motor DT were significantly slower than those performed singularly (p < 0.01). The GPT performed with the cognitive task was slower than the secondary motor task (p < 0.05). A training effect was present up to the 4th consecutive trial. ConclusionsThe GPT can be executed with a cognitive or motor task to increase the difficulty of the trial to better evaluate manual dexterity and cognitive capacities.

Maximal force production requires OPTIMAL conditions

The OPTIMAL theory of motor learning identifies several motivational and attentional factors that draw out latent motor performance capabilities. One implication of the OPTIMAL theory of motor learning (Wulf & Lewthwaite, 2016) is that standardized motor performance assessments likely do not reflect maximal capabilities unless they are "optimized" with appropriate testing conditions. The present study examined the effects of three key motivational (enhanced expectancies, EE, and autonomy support, AS) and attentional (external focus, EF) variables in the OPTIMAL theory on maximum force production. In Experiment 1, a handgrip strength task was used. EE, AS, and EF were implemented, in a counterbalanced order, on consecutive trial blocks in an optimized group. A control group performed all blocks under neutral conditions. While there were no group differences on Block 1 (baseline), the optimized group outperformed the control group on all other blocks. In Experiment 2, participants performed two one-repetition maximum (1-RM) squat lift tests, separated by one week. Two groups, an optimized group and control group, had similar 1-RM values on the first test performed under neutral conditions. However, on the second test, a group performing under optimized conditions (EE, AS, EF) showed an increase in 1-RM, while there was no change from the first to the second test for a control group. We argue that standard test conditions may not produce true maximal performance. The findings corroborate the importance of key factors in the OPTIMAL theory and should be applied to ensure accurate strength performance assessment.

Prediction of pathological complete response in breast cancer patients during neoadjuvant chemotherapy: Is shear wave elastography a useful tool in clinical routine?

ObjectiveTo compare the validity of Shear Wave Elastography (SWE) for the preoperative assessment of pathological complete response (pCR) to standard clinical assessment in breast cancer patients undergoing neoadjuvant chemotherapy (NACT). Materials and MethodsThis prospective, consecutive clinical trial was conducted under routine clinical practice. Analysis included 134 patients. SWE served as index test, final pathology from surgical specimen as reference standard. PCR (ypT0) was defined as primary endpoint. Elasticity changes were compared for the pCR- vs. non-pCR group. To determine the validity of shear wave velocity (Vs), ROC analyses and diagnostic accuracy parameters were calculated and compared to the final standard clinical assessment by physical examination, mammography and B-mode ultrasound (ycT + vs. ycT0). ResultsVs was significantly reduced in pCR and non-pCR groups during NACT (pCR: ΔVs(abs) = 3.90 m/s, p < 0.001; non-pCR: ΔVs(abs) = 3.10 m/s, p < 0.001). The pCR-group showed significant lower Vs for all control visits (t1,2,END: p < 0.001). ROC analysis of Vs yielded moderate AUCs for the total population (t0: 0.613, t1: 0.745, t2: 0.685, tEND: 0.718). Compared to standard clinical assessment, Vs(tEND) (cut-off: ≤3.35 m/s) was superior in sensitivity (79.6 % vs. 54.5 %), NPV (86.4 % vs. 77.5 %), FNR (20.4 % vs. 45.5 %), inferior in specificity (58.6 % vs. 77.5 %), PPV (46.3 % vs. 54.5 %), FPR (41.4 % vs. 22.5 %). ConclusionSWE measures significant differences in tumour elasticity changes in pCR vs. non-pCR cases. SWE shows improved sensitivity compared to standard clinical assessment, high NPV and low FNR, but failed in specificity in order to predict pCR under routine conditions.

A novel porous Fe3O4/Titanosilicate/g-C3N4 ternary nanocomposites: Synthesis, characterization and their enhanced photocatalytic activity on Rhodamine B degradation under sunlight irradiation

A magnetically separable Fe3O4/porous Titanosilicate/g-C3N4 hybrid nanocomposite (FTSCN) has been synthesized by a facile in-situ method. The synthesized nanocomposites are characterized by PXRD, FE-SEM, TEM, BET-Surface area, FT-IR, UV–vis., photoluminescence, magnetic susceptibility and photocatalytic activity. XRD, FE-SEM, TEM, FT-IR, results of FTSCN show that the formation of finely distributed Fe3O4 nanoparticles in the titanosilicate matrix and g-C3N4. BET-surface area shows that the enhancement of surface area on heterojunction. The bandwidth is calculated from diffuse reflectance ultraviolet-visible spectroscopy. The enhancement of electron-hole pair formation is observed fluorescence spectroscopy. The magnetic behaviour is also observed by magnetic susceptibility test of the nanocomposite. FTSCN nanocomposite exhibit improved photodegradation of Rhodamine B sunlight light irradiation. The ideal photocatalytic activity of FTSCN3.5 in presence of sunlight is nearly 4 to 5-fold greater than pure Fe3O4 (FO), pure titanosilicate (TS) and g-C3N4 respectively. We confirmed that the prepared FTSCN3.5 hybrid photocatalyst is very stable even after five consecutive trial runs are observed by XRD spectral data. The enhanced photocatalytic behaviour of the FTSCN3.5 hybrid nanocomposite in the presence of sunlight is because of the synergistic effect of the Fe3O4, pure titanosilicate and g-C3N4. A plausible, structure of heterojunction, physical and chemical catalytic mechanisms are also proposed.