Genomic-transcriptomic evolution in lung cancer and metastasis.

Intratumour heterogeneity (ITH) fuels lung cancer evolution, which leads to immune evasion and resistance to therapy1. Here, using paired whole-exome and RNA sequencing data, we investigate intratumour transcriptomic diversity in 354 non-small cell lung cancer tumours from 347 out of the first 421 patients prospectively recruited into the TRACERx study2,3. Analyses of 947 tumour regions, representing both primary and metastatic disease, alongside 96 tumour-adjacent normal tissue samples implicate the transcriptome as a major source of phenotypic variation. Gene expression levels and ITH relate to patterns of positive and negative selection during tumour evolution. We observe frequent copy number-independent allele-specific expression that is linked to epigenomic dysfunction. Allele-specific expression can also result in genomic-transcriptomic parallel evolution, which converges on cancer gene disruption. We extract signatures of RNA single-base substitutions and link their aetiology to the activity of the RNA-editing enzymes ADAR and APOBEC3A, thereby revealing otherwise undetected ongoing APOBEC activity in tumours. Characterizing the transcriptomes of primary-metastatic tumour pairs, we combine multiple machine-learning approaches that leverage genomic and transcriptomic variables to link metastasis-seeding potential to the evolutionary context of mutations and increased proliferation within primary tumour regions. These results highlight the interplay between the genome and transcriptome in influencing ITH, lung cancer evolution and metastasis.

Monolithically integrated 112 Gbps PAM4 optical transmitter and receiver in a 45†nm CMOS-silicon photonics process.

We demonstrate a transmitter and receiver in a silicon photonics platform for O-band optical communication that monolithically incorporates a modulator driver, traveling-wave Mach-Zehnder modulator, control circuitry, photodetector, and transimpedance amplifier (TIA) in the GlobalFoundries Fotonix (45SPCLO) platform. The transmitter and receiver show an open 112 Gbps PAM4 eye at a 4.3 pJ/bit energy efficiency, not including the laser. Extensive use of gain-peaking enables our modulator driver and TIA to achieve the high bandwidths needed in the 45 nm CMOS-silicon photonics process. Our results suggest an alternative to the frequent approach of bump-bonding BiCMOS drivers and TIAs to silicon photonics.

Electroconvulsive therapy, electric field, neuroplasticity, and clinical outcomes.

Electroconvulsive therapy (ECT) remains the gold-standard treatment for patients with depressive episodes, but the underlying mechanisms for antidepressant response and procedure-induced cognitive side effects have yet to be elucidated. Such mechanisms may be complex and involve certain ECT parameters and brain regions. Regarding parameters, the electrode placement (right unilateral or bitemporal) determines the geometric shape of the electric field (E-field), and amplitude determines the E-field magnitude in select brain regions (e.g., hippocampus). Here, we aim to determine the relationships between hippocampal E-field strength, hippocampal neuroplasticity, and antidepressant and cognitive outcomes. We used hippocampal E-fields and volumes generated from a randomized clinical trial that compared right unilateral electrode placement with different pulse amplitudes (600, 700, and 800 mA). Hippocampal E-field strength was variable but increased with each amplitude arm. We demonstrated a linear relationship between right hippocampal E-field and right hippocampal neuroplasticity. Right hippocampal neuroplasticity mediated right hippocampal E-field and antidepressant outcomes. In contrast, right hippocampal E-field was directly related to cognitive outcomes as measured by phonemic fluency. We used receiver operating characteristic curves to determine that the maximal right hippocampal E-field associated with cognitive safety was 112.5 V/m. Right hippocampal E-field strength was related to the whole-brain ratio of E-field strength per unit of stimulation current, but this whole-brain ratio was unrelated to antidepressant or cognitive outcomes. We discuss the implications of optimal hippocampal E-field dosing to maximize antidepressant outcomes and cognitive safety with individualized amplitudes.

Accelerated mineral bio-carbonation of coarse residue kimberlite material by inoculation with photosynthetic microbial mats.

Microbiological weathering of coarse residue deposit (CRD) kimberlite produced by the Venetia Diamond Mine, Limpopo, South Africa enhanced mineral carbonation relative to untreated material. Cultures of photosynthetically enriched biofilm produced maximal carbonation conditions when mixed with kimberlite and incubated under near surface conditions. Interestingly, mineral carbonation also occurred in the dark, under water-saturated conditions. The examination of mineralized biofilms in ca. 150 µm-thick-sections using light microscopy, X-ray fluorescence microscopy (XFM) and backscatter electron-scanning electron microscopy-energy dispersive x-ray spectrometry demonstrated that microbiological weathering aided in producing secondary calcium/magnesium carbonates on silicate grain boundaries. Calcium/magnesium sulphate(s) precipitated under vadose conditions demonstrating that evaporites formed upon drying. In this system, mineral carbonation was only observed in regions possessing bacteria, preserved within carbonate as cemented microcolonies. 16S rDNA molecular diversity of bacteria in kimberlite and in natural biofilms growing on kimberlite were dominated by Proteobacteria that are active in nitrogen, phosphorus and sulphur cycling. Cyanobacteria based enrichment cultures provided with nitrogen & phosphorus (nutrients) to enhance growth, possessed increased diversity of bacteria, with Proteobacteria re-establishing themselves as the dominant bacterial lineage when incubated under dark, vadose conditions consistent with natural kimberlite. Overall, 16S rDNA analyses revealed that weathered kimberlite hosts a diverse microbiome consistent with soils, metal cycling and hydrocarbon degradation. Enhanced weathering and carbonate-cemented microcolonies demonstrate that microorganisms are key to mineral carbonation of kimberlite.

Discovery of 17 conserved structural RNAs in fungi.

Many non-coding RNAs with known functions are structurally conserved: their intramolecular secondary and tertiary interactions are maintained across evolutionary time. Consequently, the presence of conserved structure in multiple sequence alignments can be used to identify candidate functional non-coding RNAs. Here, we present a bioinformatics method that couples iterative homology search with covariation analysis to assess whether a genomic region has evidence of conserved RNA structure. We used this method to examine all unannotated regions of five well-studied fungal genomes (Saccharomyces cerevisiae, Candida albicans, Neurospora crassa, Aspergillus fumigatus, and Schizosaccharomyces pombe). We identified 17 novel structurally conserved non-coding RNA candidates, which include four H/ACA box small nucleolar RNAs, four intergenic RNAs and nine RNA structures located within the introns and untranslated regions (UTRs) of mRNAs. For the two structures in the 3' UTRs of the metabolic genes GLY1 and MET13, we performed experiments that provide evidence against them being eukaryotic riboswitches.

Physiological responses and performance factors for double-poling and diagonal-stride treadmill roller-skiing time-trial exercise.

PURPOSE: To compare physiological responses between a self-paced 4-min double-poling (DP) time-trial (TTDP) versus a 4-min diagonal-stride (DS) time-trial (TTDS). The relative importance of peak oxygen uptake ([Formula: see text]O2peak), anaerobic capacity, and gross efficiency (GE) for projection of 4-min TTDP and TTDS roller-skiing performances were also examined. METHODS: Sixteen highly trained male cross-country skiers performed, in each sub-technique on separate occasions, an 8 × 4-min incremental submaximal protocol, to assess individual metabolic rate (MR) versus power output (PO) relationships, followed by a 10-min passive break and then the TTDP or TTDS, with a randomized order between sub-techniques. RESULTS: In comparison to TTDS, the TTDP resulted in 10 ± 7% lower total MR, 5 ± 4% lower aerobic MR, 30 ± 37% lower anaerobic MR, and 4.7 ± 1.2 percentage points lower GE, which resulted in a 32 ± 4% lower PO (all P < 0.01). The [Formula: see text]O2peak and anaerobic capacity were 4 ± 4% and 30 ± 37% lower, respectively, in DP than DS (both P < 0.01). The PO for the two time-trial (TT) performances were not significantly correlated (R2 = 0.044). Similar parabolic pacing strategies were used during both TTs. Multivariate data analysis projected TT performance using [Formula: see text]O2peak, anaerobic capacity, and GE (TTDP, R2 = 0.974; TTDS, R2 = 0.848). The variable influence on projection values for [Formula: see text]O2peak, anaerobic capacity, and GE were for TTDP, 1.12 ± 0.60, 1.01 ± 0.72, and 0.83 ± 0.38, respectively, and TTDS, 1.22 ± 0.35, 0.93 ± 0.44, and 0.75 ± 0.19, respectively. CONCLUSIONS: The results show that a cross-country skier's "metabolic profile" and performance capability are highly sub-technique specific and that 4-min TT performance is differentiated by physiological factors, such as [Formula: see text]O2peak, anaerobic capacity, and GE.

Narrative structure of A Song of Ice and Fire creates a fictional world with realistic measures of social complexity.

Network science and data analytics are used to quantify static and dynamic structures in George R. R. Martin's epic novels, A Song of Ice and Fire, works noted for their scale and complexity. By tracking the network of character interactions as the story unfolds, it is found that structural properties remain approximately stable and comparable to real-world social networks. Furthermore, the degrees of the most connected characters reflect a cognitive limit on the number of concurrent social connections that humans tend to maintain. We also analyze the distribution of time intervals between significant deaths measured with respect to the in-story timeline. These are consistent with power-law distributions commonly found in interevent times for a range of nonviolent human activities in the real world. We propose that structural features in the narrative that are reflected in our actual social world help readers to follow and to relate to the story, despite its sprawling extent. It is also found that the distribution of intervals between significant deaths in chapters is different to that for the in-story timeline; it is geometric rather than power law. Geometric distributions are memoryless in that the time since the last death does not inform as to the time to the next. This provides measurable support for the widely held view that significant deaths in A Song of Ice and Fire are unpredictable chapter by chapter.

Pneumomediastinum in COVID-19: a phenotype of severe COVID-19 pneumonitis? The results of the United Kingdom (POETIC) survey.

BACKGROUND: There is an emerging understanding that coronavirus disease 2019 (COVID-19) is associated with increased incidence of pneumomediastinum. We aimed to determine its incidence among patients hospitalised with COVID-19 in the United Kingdom and describe factors associated with outcome. METHODS: A structured survey of pneumomediastinum and its incidence was conducted from September 2020 to February 2021. United Kingdom-wide participation was solicited via respiratory research networks. Identified patients had SARS-CoV-2 infection and radiologically proven pneumomediastinum. The primary outcomes were to determine incidence of pneumomediastinum in COVID-19 and to investigate risk factors associated with patient mortality. RESULTS: 377 cases of pneumomediastinum in COVID-19 were identified from 58 484 inpatients with COVID-19 at 53 hospitals during the study period, giving an incidence of 0.64%. Overall 120-day mortality in COVID-19 pneumomediastinum was 195/377 (51.7%). Pneumomediastinum in COVID-19 was associated with high rates of mechanical ventilation. 172/377 patients (45.6%) were mechanically ventilated at the point of diagnosis. Mechanical ventilation was the most important predictor of mortality in COVID-19 pneumomediastinum at the time of diagnosis and thereafter (p<0.001) along with increasing age (p<0.01) and diabetes mellitus (p=0.08). Switching patients from continuous positive airways pressure support to oxygen or high flow nasal oxygen after the diagnosis of pneumomediastinum was not associated with difference in mortality. CONCLUSIONS: Pneumomediastinum appears to be a marker of severe COVID-19 pneumonitis. The majority of patients in whom pneumomediastinum was identified had not been mechanically ventilated at the point of diagnosis.

Postradioiodine Graves' management: The PRAGMA study.

OBJECTIVE: Thyroid status in the months following radioiodine (RI) treatment for Graves' disease can be unstable. Our objective was to quantify frequency of abnormal thyroid function post-RI and compare effectiveness of common management strategies. DESIGN: Retrospective, multicentre and observational study. PATIENTS: Adult patients with Graves' disease treated with RI with 12 months' follow-up. MEASUREMENTS: Euthyroidism was defined as both serum thyrotropin (thyroid-stimulating hormone [TSH]) and free thyroxine (FT4) within their reference ranges or, when only one was available, it was within its reference range; hypothyroidism as TSH ≥ 10 mU/L, or subnormal FT4 regardless of TSH; hyperthyroidism as TSH below and FT4 above their reference ranges; dysthyroidism as the sum of hypo- and hyperthyroidism; subclinical hypothyroidism as normal FT4 and TSH between the upper limit of normal and <10 mU/L; and subclinical hyperthyroidism as low TSH and normal FT4. RESULTS: Of 812 patients studied post-RI, hypothyroidism occurred in 80.7% and hyperthyroidism in 48.6% of patients. Three principal post-RI management strategies were employed: (a) antithyroid drugs alone, (b) levothyroxine alone, and (c) combination of the two. Differences among these were small. Adherence to national guidelines regarding monitoring thyroid function in the first 6 months was low (21.4%-28.7%). No negative outcomes (new-onset/exacerbation of Graves' orbitopathy, weight gain, and cardiovascular events) were associated with dysthyroidism. There were significant differences in demographics, clinical practice, and thyroid status postradioiodine between centres. CONCLUSIONS: Dysthyroidism in the 12 months post-RI was common. Differences between post-RI strategies were small, suggesting these interventions alone are unlikely to address the high frequency of dysthyroidism.

The Gore Cardioform Atrial Septal Defect Occluder: A novel solution to the management of severe hemolysis following transcatheter septal defect closure.

Significant hemolysis is a recognized complication of transcatheter high-velocity shunt occlusion using some Amplatzer devices. We describe a case of severe hemolysis following occlusion of an iatrogenic Gerbode defect with an Amplatzer muscular ventricular septal defect occluder successfully managed by transcatheter device removal and reocclusion with a Gore Cardioform Atrial Septal Defect Occluder.

Late Outcomes of Transcatheter Coarctation Intervention in Infants with Biventricular Anatomy.

Determine outcomes of catheter intervention for aortic coarctation in infants. Aortic coarctation in infants following surgical repair and in high surgical risk native cases remains a challenging problem. Catheter intervention is an alternative to surgical intervention. Single-center, chart review of infants with biventricular anatomy who underwent coarctation stent placement or balloon angioplasty between 04/2004 and 04/2020. Outcomes of interest included change in aortic lumen diameter, peak gradient, number of re-interventions, time to re-intervention, and adverse events. Thirty-four patients were included in analysis, of those 16 underwent stent placement. Patients' mean age was 4.0 ± 3.0 months and weight of 5.3 ± 1.9 kg. Follow-up interval was 5.4 ± 5.1 years (0.2-16.1 years). Twelve (35%) patients underwent procedure due to ventricular dysfunction; the rest were for high resting gradient. Coarctation diameter increased from 2.4 ± 1.0 to 4.5 ± 1.3 (p < 0.01) and gradient decreased from 32.0 ± 18.4 mmHg to 9.2 ± 8.8 mmHg (p < 0.01). Thirteen (81%) of the stented patients required at least one re-intervention, at an average of 1.7 ± 3.2 years from the index procedure. Five (28%) of those undergoing balloon angioplasty required repeat intervention. There was no mortality due to the procedure and one late mortality. One patient had a serious procedural adverse event. On follow-up, 12 (35%) were on anti-hypertensive medications. Catheter intervention, including stent placement, for aortic coarctation in infants is feasible with an acceptable adverse event profile. Repeat interventions are common.

Comparison of the effects of velocity-based vs. traditional resistance training methods on adaptations in strength, power, and sprint speed: A systematic review, meta-analysis, and quality of evidence appraisal.

We estimated the effectiveness of using velocity feedback to regulate resistance training load on changes in muscle strength, power, and linear sprint speed in apparently healthy participants. Academic and grey literature databases were systematically searched to identify randomised trials that compared a velocity-based training intervention to a 'traditional' resistance training intervention that did not use velocity feedback. Standardised mean differences (SMDs) were pooled using a random effects model. Risk of bias was assessed with the Risk of Bias 2 tool and the quality of evidence was evaluated using the GRADE approach. Four trials met the eligibility criteria, comprising 27 effect estimates and 88 participants. The main analyses showed trivial differences and imprecise interval estimates for effects on muscle strength (SMD 0.06, 95% CI -0.51-0.63; I2 = 42.9%; 10 effects from 4 studies; low-quality evidence), power (SMD 0.11, 95% CI -0.28-0.49; I2 = 13.5%; 10 effects from 3 studies; low-quality evidence), and sprint speed (SMD -0.10, 95% CI -0.72-0.53; I2 = 30.0%; 7 effects from 2 studies; very low-quality evidence). The results were robust to various sensitivity analyses. In conclusion, there is currently no evidence that VBT and traditional resistance training methods lead to different alterations in muscle strength, power, or linear sprint speed.

Response of US psychiatric programs to the COVID-19 pandemic and the impact on trainees.

BACKGROUND: Medical training program and hospital response to the COVID-19 pandemic has varied greatly and has impacted trainee well-being. Which factors have specifically related to trainee wellness, however, has not yet been examined in depth. The aim of the study was to understand trainee perspectives on the individual psychiatry trainee programs' hospitals' objective COVID-19 preparedness management. We also sought and to gauge how program changes, and general pandemic-related concerns, have been associated with trainee satisfaction and burnout. METHODS: A cross-sectional survey study of psychiatric trainees was distributed electronically throughout the country via various psychiatry residency program listservs in April 2020. Statistical analyses were performed utilizing simple linear regression. RESULTS: From 352 respondents (346 complete responses and 6 partial responses), the most frequent program changes were "decreased number of rotations requiring in-person patient care" and "increased call hours or duties." Of pandemic-related concerns surveyed, the two greatest were "spreading COVID-19 to family/friends" and "co-residents' burnout and anxiety." A positive relationship was found between trainee satisfaction with perceived COVID-19 departmental response and comfort level of residents/fellows in expressing concerns with attending clinicians and department leadership. CONCLUSIONS: Since the start of the COVID-19 pandemic, trainees have experienced a variety of changes to trainee program policies and guidelines. Overall, poor communication and trainee dissatisfaction with departmental response correlated with concern of infection and anxiety/burnout. Insights garnered from this study could provide scaffolding for the best practices to reduce trainee physician anxiety/burnout for the current and future pandemics of this variety and magnitude.

Using Genomic Selection to Develop Performance-Based Restoration Plant Materials.

Effective native plant materials are critical to restoring the structure and function of extensively modified ecosystems, such as the sagebrush steppe of North America's Intermountain West. The reestablishment of native bunchgrasses, e.g., bluebunch wheatgrass (Pseudoroegneria spicata [Pursh] À. Löve), is the first step for recovery from invasive species and frequent wildfire and towards greater ecosystem resiliency. Effective native plant material exhibits functional traits that confer ecological fitness, phenotypic plasticity that enables adaptation to the local environment, and genetic variation that facilitates rapid evolution to local conditions, i.e., local adaptation. Here we illustrate a multi-disciplinary approach based on genomic selection to develop plant materials that address environmental issues that constrain local populations in altered ecosystems. Based on DNA sequence, genomic selection allows rapid screening of large numbers of seedlings, even for traits expressed only in more mature plants. Plants are genotyped and phenotyped in a training population to develop a genome model for the desired phenotype. Populations with modified phenotypes can be used to identify plant syndromes and test basic hypotheses regarding relationships of traits to adaptation and to one another. The effectiveness of genomic selection in crop and livestock breeding suggests this approach has tremendous potential for improving restoration outcomes for species such as bluebunch wheatgrass.

Electrical actuation of dielectric droplets by negative liquid dielectrophoresis.

This paper presents an electrical actuation scheme of dielectric droplet by negative liquid dielectrophoresis. A general model of lumped parameter electromechanics for evaluating the electromechanical force acting on the droplets is established. The model reveals the influence of actuation voltage, device geometry, and dielectric parameter on the actuation force for both conductive and dielectric medium. Using this model, we compare the actuation forces for four liquid combinations in the parallel-plate geometry and predict the low voltage actuation of dielectric droplets by negative dielectrophoresis. Parallel experimental results demonstrate such electric actuation of dielectric droplets, including droplet transport, splitting, merging, and dispending. All these dielectric droplet manipulations are achieved at voltages < 100 Vrms . The frequency dependence of droplet actuation velocity in aqueous solution is discussed and the existence of surfactant molecules is believed to play an important role by realigning with the AC electric field. Finally, we present coplanar manipulation of oil and water droplets and formation of oil-in-water emulsion droplet by applying the same low voltage.

Comparison of the investigational device exemption and post-approval trials of the Melody transcatheter pulmonary valve.

OBJECTIVE: We compared 5-year outcomes of transcatheter pulmonary valve (TPV) replacement with the Melody TPV in the post-approval study (PAS) and the investigational device exemption (IDE) trial. BACKGROUND: As a condition of approval of the Melody TPV after the IDE trial, the Food and Drug Administration required that a PAS be conducted to evaluate outcomes of TPV replacement in a "real-world" environment. The 5-year outcomes of the PAS have not been published, and the IDE and PAS trials have not been compared. METHODS: The cohorts comprised all patients catheterized and implanted at 5 IDE sites and 10 PAS sites. Differences in trial protocols were detailed. Time-related outcomes and valve-related adverse events were compared between the two trials with Kaplan-Meier curves and log-rank testing. RESULTS: 167 patients (median age, 19 years) were catheterized and 150 underwent TPV replacement in the IDE trial; 121 were catheterized (median age, 17 years) and 100 implanted in the PAS. Freedom from hemodynamic dysfunction (p = .61) or any reintervention (p = .74) over time did not differ between trials. Freedom from stent fracture (p = .003) and transcatheter reintervention (p = .010) were longer in PAS, whereas freedom from explant (p = .020) and TPV endocarditis (p = .007) were shorter. Clinically important adverse events (AEs) were reported in 14% of PAS and 7.2% of IDE patients (p = .056); the incidence of any particular event was low in both. CONCLUSIONS: Hemodynamic and time-related outcomes in the PAS and IDE trials were generally similar, confirming the effectiveness of the Melody TPV with real-world providers. There were few significant complications and limited power to identify important differences in AEs. The lack of major differences in outcomes between the two studies questions the usefulness of mandated costly post-approval studies as part of the regulatory process for Class III medical devices.

Electroconvulsive Therapy Pulse Amplitude and Clinical Outcomes.

INTRODUCTION: Electroconvulsive therapy (ECT) pulse amplitude, which determines the induced electric field magnitude in the brain, is currently set at 800-900 milliamperes (mA) on modern ECT devices without any clinical or scientific rationale. The present study assessed differences in depression and cognitive outcomes for three different pulse amplitudes during an acute ECT series. We hypothesized that the lower amplitudes would maintain the antidepressant efficacy of the standard treatment and reduce the risk of neurocognitive impairment. METHODS: This double-blind investigation randomized subjects to three treatment arms: 600, 700, and 800 mA (active comparator). Clinical, cognitive, and imaging assessments were conducted pre-, mid- and post-ECT. Subjects had a diagnosis of major depressive disorder, age range between 50 and 80 years, and met clinical indication for ECT. RESULTS: The 700 and 800 mA arms had improvement in depression outcomes relative to the 600 mA arm. The amplitude groups showed no differences in the primary cognitive outcome variable, the Hopkins Verbal Learning Test-Revised (HVLT-R) retention raw score. However, secondary cognitive outcomes such as the Delis Kaplan Executive Function System Letter and Category Fluency measures demonstrated cognitive impairment in the 800 mA arm. DISCUSSION: The results demonstrated a dissociation of depression (higher amplitudes better) and cognitive (lower amplitudes better) related outcomes. Future work is warranted to elucidate the relationship between amplitude, electric field, neuroplasticity, and clinical outcomes.

The dose-response relationship between interval-training and VO2max in well-trained endurance runners: A systematic review.

Success in endurance running is primarily determined by maximal aerobic power (VO2max), fractional utilization, and running economy (RE). Within the literature, two training modalities have been identified to improve VO2max; continuous training (CT) and interval-training (IT). The efficacy of IT to improve VO2max in well-trained runners remains equivocal, as does whether a dose-response relationship exists between the IT training load performed and changes in VO2max. A keyword search was performed in five electronic databases. Seven studies met the inclusion criteria for this systematic review. The training impulse (TRIMP) was calculated to analyse relationships between training load and changes in VO2max, by calculating the time accumulated in certain intensity domains throughout a training intervention. Non-significant (P>0.05) improvements in VO2max were reported in six studies, with only one study reporting a significant (P<0.05) improvement following the IT interventions. A relationship between the training session impulse of the interval-training performed (IT STRIMP) and VO2max improvements were observed. The efficacy of IT to improve VO2max in well-trained runners remains equivocal, nevertheless, the novel method of training-load analysis demonstrates a relationship between the IT STRIMP and VO2max improvements. This provides practical application for the periodization of IT within the training regime of well-trained distance runners.

Development in Adolescent Middle-Distance Athletes: A Study of Training Loadings, Physical Qualities, and Competition Performance.

ABSTRACT: Jones, TW, Shillabeer, BC, Ryu, JH, and Cardinale, M. Development in adolescent middle-distance athletes: a study of training loadings, physical qualities, and competition performance. J Strength Cond Res 35(12S): S103-S110, 2021-The purpose of this study was to examine changes in running performance and physical qualities related to middle-distance performance over a training season. The study also examined relationships between training loading and changes in physical qualities as assessed by laboratory and field measures. Relationships between laboratory and field measures were also analyzed. This was a 9-month observational study of 10 highly trained adolescent middle-distance athletes. Training intensity distribution was similar over the observational period, whereas accumulated and mean distance and training time and accumulated load varied monthly. Statistically significant (p < 0.05) and large effect sizes (Cohen's d) (>0.80) were observed for improvements in: body mass (5.6%), 600-m (4.6%), 1,200-m (8.7%), and 1,800-m (6.1%) time trial performance, critical speed (7.1%), V̇o2max (5.5%), running economy (10.1%), vertical stiffness (2.6%), reactive index (3.8%), and countermovement jump power output relative to body mass (7.9%). Improvements in 1,800 m TT performance were correlated with increases in V̇o2max (r = 0.810, p = 0.015) and critical speed (r = 0.918, p = 0.001). Increases in V̇o2max and critical speed were also correlated (r = 0.895, p = 0.003). Data presented here indicate that improvements in critical speed may be reflective of changes in aerobic capacity in adolescent middle-distance athletes.

A Bivalent Meningococcal B Vaccine in Adolescents and Young Adults.

BACKGROUND: MenB-FHbp is a licensed meningococcal B vaccine targeting factor H-binding protein. Two phase 3 studies assessed the safety of the vaccine and its immunogenicity against diverse strains of group B meningococcus. METHODS: We randomly assigned 3596 adolescents (10 to 18 years of age) to receive MenB-FHbp or hepatitis A virus vaccine and saline and assigned 3304 young adults (18 to 25 years of age) to receive MenB-FHbp or saline at baseline, 2 months, and 6 months. Immunogenicity was assessed in serum bactericidal assays that included human complement (hSBAs). We used 14 meningococcal B test strains that expressed vaccine-heterologous factor H-binding proteins representative of meningococcal B epidemiologic diversity; an hSBA titer of at least 1:4 is the accepted correlate of protection. The five primary end points were the proportion of participants who had an increase in their hSBA titer for each of 4 primary strains by a factor of 4 or more and the proportion of those who had an hSBA titer at least as high as the lower limit of quantitation (1:8 or 1:16) for all 4 strains combined after dose 3. We also assessed the hSBA responses to the primary strains after dose 2; hSBA responses to the 10 additional strains after doses 2 and 3 were assessed in a subgroup of participants only. Safety was assessed in participants who received at least one dose. RESULTS: In the modified intention-to-treat population, the percentage of adolescents who had an increase in the hSBA titer by a factor of 4 or more against each primary strain ranged from 56.0 to 85.3% after dose 2 and from 78.8 to 90.2% after dose 3; the percentages of young adults ranged from 54.6 to 85.6% and 78.9 to 89.7%, after doses 2 and 3, respectively. Composite responses after doses 2 and 3 in adolescents were 53.7% and 82.7%, respectively, and those in young adults were 63.3% and 84.5%, respectively. Responses to the 4 primary strains were predictive of responses to the 10 additional strains. Most of those who received MenB-FHbp reported mild or moderate pain at the vaccination site. CONCLUSIONS: MenB-FHbp elicited bactericidal responses against diverse meningococcal B strains after doses 2 and 3 and was associated with more reactions at the injection site than the hepatitis A virus vaccine and saline. (Funded by Pfizer; ClinicalTrials.gov numbers, NCT01830855 and NCT01352845 ).