Search

T. C. Chao (1888–1979) was a leading Chinese Protestant theologian renowned for his creative works of Chinese theology. Although scholars have traced significant changes and shifts in Chao's theology in the 1940s, a particular formal aspect of his mature thinking has not received the attention it deserves. Chao began to emphasise and practise a particular form of Chinese theology in the 1940s and early 1950s, namely, doctrinal or dogmatic theology. This paper traces the development of Chao's dogmatic theology and examines one representative dogmatic locus in his thinking, the doctrine of the Trinity. It argues that Chao's turn to dogmatics not only richly illuminates a crucial aspect of his mature life and thought, but also sheds light on the legacy of Andrew Walls, whose work highlights Christianity's cross-cultural diffusion and the gospel's encounter with the cultural worlds it takes root within. [ABSTRACT FROM AUTHOR]

Issues addressed: To determine cardiovascular health benefits in Indigenous men following short‐duration small‐sided games. Methods: Fourteen sedentary Indigenous males (35.6 SD 7.2 years), randomly assigned to a small‐sided games (SSG) or a non‐exercising control. Small‐sided 20‐minute (4 × 5 minute bouts) games of touch football were played 2 x/week for 9 weeks. Waist and hip circumferences, height, total body mass (kg), fat (%), fat free mass (kg), muscle mass (kg), resting heart rate (bpm), systolic blood pressure (mmHg), total cholesterol and high‐density lipid concentrations were measured and waist‐hip ratios, body mass index (BMI), heart rate variability (HRV), metabolic age and Framingham risk calculated before and after the exercise intervention. Between group differences were examined using unpaired t tests (welch corrected) and described using Cohen's effect size (ES) differences (corrected to determine hedges g). Results: Significant between group differences favouring the SSG group were observed in body mass (P =.039, ES = 0.18), BMI (P =.031, ES = 0.22) and metabolic age (P =.033, ES = 0.29) and in HRV parameters of approximate entropy (ApEN; P =.01, ES = 1.65) and sample entropy (SampEN; P =.0193, ES = 1.40). Conclusion: Middle‐aged Indigenous men can gain cardiovascular health benefits following short bouts of small‐sided game play accumulating in 40‐minutes of exercise each week. So what?: Short‐duration SSG may address many exercise barriers, and offer a sustainable form of exercise to improve cardiovascular health amongst Indigenous men. [ABSTRACT FROM AUTHOR]

"Untimely Love" reassesses the aesthetic choices and political implications of Edith Wharton's The Age of Innocence (1920), first by highlighting a surprising overlap between Wharton and the anarcho-feminist Emma Goldman. Wharton's novelistic critique of New York society's marriage rituals, spurred by an unconsummated affair between Newland Archer and his wife's cousin Ellen Olenska, follows Goldman in positing an antagonism between the hierarchies of marriage and the equalizing nature of love. For Wharton, however, this antagonism will not be resolved with free love one day triumphing. To explain her position, the article turns to Jacques Ranciere's unresolvable antagonism between "politics" and "the police,"which has an aesthetic analogue in the clash between the formally anarchic modern novel and premodern hierarchies of genre. Wharton unearths 1870s New York like an archeologist to expose how its patriarchal logic polices women's sexuality within and outside marriage, making expressions of love quite rare. Wharton unleashes the disruptive power of love through formal experimentation, temporarily subverting her own historical realism, when she has Ellen and Archer visit the Metropolitan Museum of Art in Central Park, which did not yet exist in the novel's timeframe. The Met's impossible location and its uncataloged holdings open to public viewing upset New York's social and aesthetic hierarchies. It is in this anachronistic anddemocratic context that Archer first sees "love visible" in the world, rearranging his entire worldview. Wharton, in a related political gesture of aesthetic dissensus, aligns her untimely lovers with themuseum's suddenly visible ghosts of history. [ABSTRACT FROM AUTHOR]

Negative capacitance FETs (NCFETs) have attracted significant interest due to their steep-switching capability at a low voltage and the associated benefits for implementing energy-efficient Boolean logic. While most existing works aim to avoid the ID – VG hysteresis in NCFETs, this paper exploits this hysteresis feature for logic-memory synergy and presents a custom-designed nonvolatile NCFET D flip-flop (DFF) that maintains its state during power outages. This paper also presents an NCFET fabricated for this purpose, showing <10 mV/decade steep hysteresisedges and high, up to seven orders inmagnitude, R\text {DS} ratio between the two polarization states. With a device-circuit codesign that takes advantage of the embedded nonvolatility and the high R\text {DS} ratio, the proposed DFF consumes negligible static current in backup and restore operations, and remains robust even with significant global and local ferroelectric material variations across a wide 0.3–0.8 V supply voltage range. Therefore, the proposed DFF achieves energy-efficient and low-latency backup and restore operations. Furthermore, it has an ultralow energy-delay overhead, below 2.1% in normal operations, and operates using the same voltage supply as the Boolean logic elements with which it connects. This promises energy-efficient nonvolatile computing in energy-harvesting and power-gating applications. [ABSTRACT FROM PUBLISHER]

A literary criticism of the novel "The Bostonians," by Henry James is presented. Topics discussed include the visits of the windows of the home of activist Olive Chancellor to catch the view and environments of Boston, Massachusetts, the introduction given by literary critic Irving Howe to the book, and the architecture and the voice of women considered by James in the book.

Objective: Firefighter physical aptitude tests were administered to unskilled subjects and operational firefighters to evaluate the impact that testing bias associated with gender, age, activity-specific skills, or task familiarity may have upon establishing performance thresholds. Methods: These tests were administered in sequence, simulating hazmat incidents, ventilation fan carriage (stairs), motor-vehicle rescues, bushfire incidents, fire attacks, and a firefighter rescue. Participants included two unskilled samples (jV=14 and 22) and 143 firefighters. Results: Firefighter performance was not significantly different from the unskilled subjects. Participants from both genders passed the test, with scores unrelated to performance skill or age; however, familiarization significantly improved performance when the test was repeated. Conclusion: These outcomes confirmed this test to be gender-, age-, and skill-neutral. Familiarization effects could be removed through performing a single, pre-selection trial of the test battery. [ABSTRACT FROM AUTHOR]

The article offers information on the U.S. Uniform Interstate Family Support Act aimed to establish and modify child support orders and addresses the enforcement of child support obligations within the country.

This investigation examines pacing during intermittent team sports. Sixteen junior Rugby League players participated in eight different small-sided offside touch games. All games were 24 min, but bout durations differed in continuous (1 × 24 min) or repeated (2 × 12, 3 × 8, 4 × 6, 6 × 4, 8 × 3, 12 × 2 or 24 × 1 min) formats. Repeat bouts were interspersed by 2 min of passive rest, and participants were informed of the bout duration immediately prior to the game. Heart rates, ratings of perceived exertion and data gathered from global positioning system devices were used to investigate the pacing strategies employed within each game. No significant (P > 0.05) between-game differences were observed in total distance; however, during the 1-min bouts, high-speed movement was significantly (P < 0.05) increased, during the first and second quarters of the 24 × 1-min game compared to all other formats (effect size range: 0.75 ± 0.61–1.38 ± 0.47). Furthermore, the rate of decline in high-speed movement over-time was greatest during the 24 × 1-min game with large differences observed between the first and third quarters (effect size: 0.90 ± 0.58). Greater moderate-speed (effect size range: 0.62 ± 0.63–1.56 ± 0.40) and less low-speed (effect size range: 0.69 ± 0.62–1.54 ± 0.40) distances were also observed during the 1-min bouts, yet heart rates were higher during the continuous 1 × 24-min game. Pacing strategies during intermittent activities are influenced by the number and duration of exercise bouts. Practitioners should consider within-game bout durations when prescribing game-based activities to improve aerobic capacity. [ABSTRACT FROM AUTHOR]

Background: Preclinical studies in mice have demonstrated that the prophylactic depletion of immunosuppressive regulatory T-cells (TRegs) through targeting the high affinity interleukin-2 (IL-2) receptor (IL-2Rα/CD25) can enhance antitumor immunotherapy. However, therapeutic approaches are complicated by the inadvertent inhibition of IL-2Rα expressing anti-tumor effector T-cells. Objective: To determine if changes in the cytokine milieu during lymphopenia may engender differential signaling requirements that would enable unarmed anti-IL-2Rα monoclonal antibody (MAbs) to selectively deplete TRegs while permitting vaccine-stimulated immune responses. Methodology: A randomized placebo-controlled pilot study was undertaken to examine the ability of the anti-IL-2Rα MAb daclizumab, given at the time of epidermal growth factor receptor variant III (EGFRvIII) targeted peptide vaccination, to safely and selectively deplete TRegs in patients with glioblastoma (GBM) treated with lymphodepleting temozolomide (TMZ). Results and Conclusions: Daclizumab treatment (n = 3) was well-tolerated with no symptoms of autoimmune toxicity and resulted in a significant reduction in the frequency of circulating CD4+Foxp3+ TRegs in comparison to saline controls (n = 3)( p = 0.0464). A significant (p<0.0001) inverse correlation between the frequency of TRegs and the level of EGFRvIII specific humoral responses suggests the depletion of TRegs may be linked to increased vaccine-stimulated humoral immunity. These data suggest this approach deserves further study. [ABSTRACT FROM AUTHOR]

Despite advances in conventional treatment modalities for malignant brain tumors-surgery, radiotherapy, and chemotherapy- the prognosis for patients with high-grade astrocytic tumor remains dismal. The highly heterogeneous and diffuse nature of astrocytic tumors calls for the development of novel therapies. Advances in genomic and proteomic research indicate that treatment of brain tumor patients can be increasingly personalized according to the characteristics of the targeted tumor and its environment. Consequently, during the last two decades, a novel class of investigative drug candidates for the treatment of central nervous system neoplasia has emerged: recombinant fusion protein conjugates armed with cytotoxic agents targeting tumor-specific antigens. The clinical applicability of the tumor-antigen-directed cytotoxic proteins as a safe and viable therapy for brain tumors is being investigated. Thus far, results fromongoing clinical trials are encouraging, as disease stabilization and patient survival prolongation have been observed in at least 109 cases. This paper summarizes the major findings pertaining to treatment with the different antiglioma cytotoxins at the preclinical and clinical stages. [ABSTRACT FROM AUTHOR]

The article discusses the law regarding child custody among divorced parents in Texas. According to the new Texas Family Code, the court may appoint a custodian who must be a suitable, competent adult, or a parent, or an authorized agency, in any suit affecting the parent-child relationship. The Code further states that a parent shall be appointed the custodian of the child unless the court finds that appointment of the parent would not be in the best interest of the child.

The author discusses the effectiveness of the intermediate-frequency alternating electric fields (AEFs) for glioblastoma treatment. Topics mentioned include the importance of public health management, the several treatment for cancer such as the maximal surgical resection, regional or systemic chemotherapy, and high-dose external-beam radiation therapy, and the patients health management.

Abstract: Conventional therapies for malignant gliomas (MGs) fail to target tumor cells exclusively, such that their efficacy is ultimately limited by non-specific toxicity. Immunologic targeting of tumor-specific gene mutations, however, may allow more precise eradication of neoplastic cells. The epidermal growth factor receptor variant III (EGFRvIII) is a consistent tumor-specific mutation that is widely expressed in MGs and other neoplasms. This mutation encodes a constitutively active tyrosine kinase that enhances tumorgenicity and migration and confers radiation and chemotherapeutic resistance. This in-frame deletion mutation splits a codon resulting in the creation of a novel glycine at the fusion junction between normally distant parts of the molecule and producing a sequence re-arrangement which creates a tumor-specific epitope for cellular or humoral immunotherapy in patients with MGs. We have previously shown that vaccination with a peptide that spans the EGFRvIII fusion junction is an efficacious immunotherapy in syngeneic murine models, but patients with MGs have a profound immunosuppression that may inhibit the ability of antigen presenting cells (APCs), even those generated ex vivo, to induce EGFRvIII-specific immune responses. In this report, we summarize our results in humans targeting this mutation in two consecutive and one multi-institutional Phase II immunotherapy trials. These trials demonstrated that vaccines targeting EGFRvIII are capable of inducing potent T- and B-cell immunity in these patients, and lead to an unexpectedly long survival time. Most importantly, vaccines targeting EGFRvIII were universally successful at eliminating tumor cells expressing the targeted antigen without any evidence of symptomatic collateral toxicity. These studies establish the tumor-specific EGFRvIII mutation as a novel target for humoral- and cell-mediated immunotherapy in a variety of cancers. The recurrence of EGFRvIII-negative tumors in our patients, however, highlights the need for targeting a broader repertoire of tumor-specific antigens. [Copyright &y& Elsevier]

The article discusses various uniform acts and model acts relating to the family law recommended by the U.S. Uniform Law Commission. The Uniform Child Abduction Prevention Act provides a valuable tool for deterring both domestic and international child abductions by parents and persons acting on behalf of the parents. The Uniform Child Custody Jurisdiction and Enforcement Act regulates interstate kidnapping of a child by the noncustodial parent. The Uniform Child Witness Testimony by Alternative Methods Act provides procedures in taking the testimony of children in criminal or civil proceedings. The Uniform Disposition of Community Property Rights at Death Act aims to preserve the rights of each spouse in property that was community property prior to a change of domicile.

This section provides information on the amendments to the Uniform Parentage Act (UPA) (2002). In August 2000, the National Conference of Commissioners on Uniform State Laws approved a totally revised version of the UPA, as originally promulgated in 1973. After the Act was withdrawn in February 2001, extended, sometimes dilatory, contact between the National Conference of Commissioners on Uniform State Laws and the American Bar Association entities continued for more than a year. Face-to-face negotiations were finally scheduled for a meeting on September 13-14, 2002 in Washington, D.C. between officials of the involved agencies. The Act was endorsed and co-sponsored by the Family Law Section, the Section of Individual Rights and Responsibilities, and the Steering Committee on Unmet Legal Needs of Children. Key to the agreed settlement is that a child born to an unmarried man and woman, including children born through assisted reproduction or in the context of a gestational agreement, should have the same rights and relationship with his or her parents or intended parents as a child born to a married couple. The promulgation of the UPA in 2000, as amended in 2002, is now the official recommendation of the Conference on the subject of parentage. There are eight articles contained in the UPA, some of which are as follows. Article 1, General Provisions, adds many new definitions to clarify the participants in determinations of parentage and adapt the Act to recent scientific developments. Article 2, Parent-Child Relationship, will look familiar to past users of UPA because it continues a number of the 1973 provisions with little or no change, while eliminating the ambiguous term natural to describe a genetic parent.

Describes a credit-card-debt activity for teaching college-level algebra students. Approach used to studying the mathematics of finance; How a teacher should begin the activity; Details on mathematical formulas.

Presents information on a study which demonstrated that he tumor-specific monoclonal antibody Y10 recognizes a murine homologue of epidermal growth factor receptor vIII. DNA synthesis and tumor cell proliferation of Y10; Materials and methods; Results and discussion.

Determines what barriers the immunogically privileged central nervous system (CNS) would pose to cytokine-assisted tumor vaccines and what cytokines would be most efficacious against tumors within the CNS. Granulocyte-macrophage colony stimulating factor (GM-CSF) and increases in mice survival; Vaccination with B16 cells producing interleukin-4.

The article offers information on oncolytic virotherapy (OV) using an oxidative stress inhibition. It informs that OV is the manipulation of replication-competent virus to selectively infect and lyse malignant cells while leaving normal cells untouched. OV represents a novel, tumor-targeted therapy for a variety of cancers intractable to current multimodality standards of care. Glioblastoma (GBM), the most aggressive of brain tumors.

Introduction The injury definitions and surveillance methods commonly used in Army basic military training (BMT) research may underestimate the extent of injury. This study therefore aims to obtain a comprehensive understanding of injuries sustained during BMT by employing recording methods to capture all physical complaints. Materials and methods Six hundred and forty-six recruits were assessed over the 12-week Australian Army BMT course. Throughout BMT injury, data were recorded via (1) physiotherapy reports following recruit consultation, (2) a member of the research team (third party) present at physical training sessions, and (3) recruit daily self-reports. Results Two hundred and thirty-five recruits had ≥1 incident injury recorded by physiotherapists, 365 recruits had ≥1 incident injury recorded by the third party, and 542 recruits reported ≥1 injury-related problems via the self-reported health questionnaire. Six hundred twenty-one, six hundred eighty-seven, and two thousand nine hundred sixty-four incident injuries were recorded from a total of 997 physiotherapy reports, 1,937 third-party reports, and 13,181 self-reported injury-related problems, respectively. The lower extremity was the most commonly injured general body region as indicated by all three recording methods. Overuse accounted for 79% and 76% of documented incident injuries from physiotherapists and the third party, respectively. Conclusions This study highlights that injury recording methods impact injury reporting during BMT. The present findings suggest that traditional injury surveillance methods, which rely on medical encounters, underestimate the injury profile during BMT. Considering accurate injury surveillance is fundamental in the sequence of injury prevention, implementing additional injury recording methods during BMT may thus improve injury surveillance and better inform training modifications and injury prevention programs. [ABSTRACT FROM AUTHOR]

Preoperative assessment is important for neurosurgical risk stratification, but the level of evidence for individual screening tests is low. In preoperative urinalysis (UA), testing may significantly increase costs and lead to inappropriate antibiotic treatment. We prospectively evaluated whether eliminating preoperative UA was noninferior to routine preoperative UA as measured by 30-day readmission for surgical site infection in adult elective neurosurgical procedures. A single-institution prospective, pragmatic study of patients receiving elective neurosurgical procedures from 2018 to 2020 was conducted. Patients were allocated based on same-day versus preoperative admission status. Rates of preoperative UA and subsequent wound infection were measured along with detailed demographic, surgical, and laboratory data. The study included 879 patients. The most common types of surgery were cranial (54.7%), spine (17.4%), and stereotactic/functional (19.5%). No preoperative UA was performed in 315 patients, while 564 underwent UA. Of tested patients, 103 (18.3%) met criteria for suspected urinary tract infection, and 69 (12.2%) received subsequent antibiotic treatment. There were 14 patients readmitted within 30 days (7 without UA [2.2%] vs. 7 with UA [1.2%]) for subsequent wound infection with a risk difference of 0.98% (95% confidence interval −0.89% to 2.85%). The upper limit of the confidence interval exceeded the preselected noninferiority margin of 1%. In this prospective study of preoperative UA for elective neurosurgical procedures using a pragmatic, real-world design, risk of readmission due to surgical site infection was very low across the study cohort, suggesting a limited role of preoperative UA for elective neurosurgical procedures. [ABSTRACT FROM AUTHOR]

Football academy settings may pose risks to adolescent athletes achieving sufficient sleep because of the contextual challenges these players face (e.g., psychosocial pressure, changes in training, competition, and academic stress). Given the importance of sleep to overall health as well as physical athletic development and injury risk, this study aimed to investigate whether differences in training schedules (morning vs. evening training sessions) affected objective measures of sleep in adolescent academy football (soccer) players. Twelve academy players (mean age 14.18 ± 1.36 years) wore an ActiGraph accelerometer on nights before, and nights of, training days in 2 separate weeks where morning (09:00-11:00 hours) and evening (18:00-20:00 hours) training occurred. Objective sleep parameters and training load data were collected. Night-time sleep periods were categorized as sleep preceding morning training, preceding evening training, or after evening training. One-way univariate and multivariate analyses of variance for repeated measures were performed to determine the impact of the training schedule on sleep. Significance levels were set at p < 0.05. The total sleep time was below the recommended guidelines (<8 hours) across conditions. A large significant effect of the training schedule on time attempted to fall asleep (p = 0.004, effect size [ES] = 0.40) and time of sleep (p = 0.003, ES = 0.41) was present, with post-evening sessions resulting in the latest times. Overall, the players' sleep behavior was resilient to changes in training schedules. However, the low sleep durations (and potential risks to physical performance/injury) suggest that sleep education coupled with practical interventions are required in this cohort. [ABSTRACT FROM AUTHOR]

Adolescent elite-level footballers are exposed to unique physical and psychological stressors which may increase injury risk, with fluctuating injury prevalence and burden. This study investigates the patterns of injury incidence and burden from 2017 to 2020 within combined pre-, start-of-, mid- and end-of-season and school-holiday phases in U13-U18 Australian male academy players. Injury incidence rate and burden were calculated for medical attention (MA), full and partial time-loss (TL) and non-time-loss (non-TL) injuries. Injury rate ratios (IRR) for injury incidences were assessed using Generalised Linear Mixed Models, and 99% confidence intervals for injury burden differences between phases. MA and non-TL injury incidence rates were higher during pre-season (IRR 1.65, p = 0.01; IRR 2.08, p = 0.02, respectively), and mid-season showed a higher non-TL incidence rate (IRR 2.15, p = 0.02) and burden (69 days with injury/1000 hrs, CI 47–103) compared to end-of-season (25 days with injury/1000 hrs, CI 15–45). MA injury rates and partial TL injury burden were higher during school compared to holiday periods (IRR 0.6, p = 0.04; 61 partial days lost/1000 hrs, CI 35–104; 13 partial days lost/1000 hrs, CI 8–23). Season phase and return-to-school may increase injury risks for elite academy footballers, and considering these phases may assist in developing injury prevention systems. [ABSTRACT FROM AUTHOR]

Several Phase II and III clinical trials have demonstrated that immunotherapy can induce objective responses in otherwise refractory malignancies in tumors outside the central nervous system. In large part, effector T cells mediate much of the antitumor efficacy in these trials, and potent antitumor T cells can be generated through vaccination, immune checkpoint blockade, adoptive transfer, and genetic manipulation. However, activated T cells must still traffic to, infiltrate, and persist within tumor in order to mediate tumor lysis. These requirements for efficacy pose unique challenges for brain tumor immunotherapy, due to specific anatomical barriers and populations of specialized immune cells within the central nervous system that function to constrain immunity. Both autoimmune and infectious diseases of the central nervous system provide a wealth of information on how T cells can successfully migrate to the central nervous system and then engender sustained immune responses. In this review, we will examine the commonalities in the efferent arm of immunity to the brain for autoimmunity, infection, and tumor immunotherapy to identify key factors underlying potent immune responses. [ABSTRACT FROM AUTHOR]

Glioblastoma is highly aggressive and remains difficult to treat despite being the most common malignant primary brain tumor in adults. Current standard-of-care treatment calls for maximum resection of the tumor mass followed by concurrent chemotherapy and radiotherapy and further adjuvant chemotherapy if necessary. Despite this regimen, prognosis remains grim. Immunotherapy has shown promising success in a variety of solid tumor types, but efficacy in glioblastoma is yet to be demonstrated. Barriers to the success of immunotherapy in glioblastoma include: a heterogeneous tumor cell population, a highly immunosuppressive microenvironment, and the blood–brain barrier, to name a few. Several immunotherapeutic approaches are actively being investigated and developed to overcome these limitations. In this review, we present different classes of immunotherapy targeting glioblastoma, their most recent results, and potential future directions. [ABSTRACT FROM AUTHOR]

In adoptive T cell transfer therapy (ACT), the antitumor efficacy of cytotoxic CD8+T lymphocytes (CTLs) has been limited by tumor-induced immunosuppression. We have demonstrated that miR-23a blockade in tumor-specific CTLs conferred resilience to TGFβ-mediated immunosuppression, resulting in superior tumor control. Our studies highlight miR-23a in tumor-specific CTLs as a clinically relevant target to enhance ACT. [ABSTRACT FROM PUBLISHER]

Objective To evaluate accuracy of a computed tomography (CT)–guided frameless stereotactic drilling and catheter system. Methods A prospective, single-arm study was performed using human cadaver heads to evaluate placement accuracy of a novel, flexible intracranial catheter and stabilizing bone anchor system and drill kit. There were 20 catheter placements included in the analysis. The primary endpoint was accuracy of catheter tip location on intraoperative CT. Secondary endpoints included target registration error and entry and target point error before and after drilling. Measurements are reported as mean ± SD (median, range). Results Target registration error was 0.46 mm ± 0.26 (0.50 mm, −1.00 to 1.00 mm). Two (10%) target point trajectories were negatively impacted by drilling. Intracranial catheter depth was 59.8 mm ± 9.4 (60.5 mm, 38.0–80.0 mm). Drilling angle was 22° ± 9 (21°, 7°–45°). Deviation between planned and actual entry point on CT was 1.04 mm ± 0.38 (1.00 mm, 0.40–2.00 mm). Deviation between planned and actual target point on CT was 1.60 mm ± 0.98 (1.40 mm, 0.40–4.00 mm). No correlation was observed between intracranial catheter depth and target point deviation (accuracy) (Pearson coefficient 0.018) or between technician experience and accuracy (Pearson coefficient 0.020). There was no significant difference in accuracy with trajectories performed for different cadaver heads ( P = 0.362). Conclusions Highly accurate catheter placement is achievable using this novel flexible catheter and bone anchor system placed via frameless stereotaxy, with an average deviation between planned and actual target point of 1.60 mm ± 0.98 (1.40 mm, 0.40–4.00 mm). [ABSTRACT FROM AUTHOR]

Human cytomegalovirus (CMV) is purportedly present in glioblastoma (GBM) while absent from the normal brain, making CMV antigens potentially ideal immunological anti-GBM targets. We recently demonstrated that patient-derived CMV pp65-specific T cells are capable of recognizing and killing autologous GBM tumor cells. This data supports CMV antigen-directed immunotherapies against GBM. [ABSTRACT FROM PUBLISHER]

Introduction Subjective measures may offer practitioners a relatively simple method to monitor recruit responses to basic military training (BMT). Yet, a lack of agreement between subjective and objective measures may presents a problem to practitioners wishing to implement subjective monitoring strategies. This study therefore aims to examine associations between subjective and objective measures of workload and sleep in Australian Army recruits. Materials and Methods Thirty recruits provided daily rating of perceived exertion (RPE) and differential RPE (d-RPE) for breathlessness and leg muscle exertion each evening. Daily internal workloads determined via heart rate monitors were expressed as Edwards training impulse (TRIMP) and average heart rate. External workloads were determined via global positioning system (PlayerLoadTM) and activity monitors (step count). Subjective sleep quality and duration was monitored in 29 different recruits via a customized questionnaire. Activity monitors assessed objective sleep measures. Linear mixed-models assessed associations between objective and subjective measures. Akaike Information Criterion assessed if the inclusion of d-RPE measures resulted in a more parsimonious model. Mean bias, typical error of the estimate (TEE) and within-subject repeated measures correlations examined agreement between subjective and objective sleep duration. Results Conditional R 2 for associations between objective and subjective workloads ranged from 0.18 to 0.78, P  < 0.01, with strong associations between subjective measures of workload and TRIMP (0.65–0.78), average heart rate (0.57–0.73), and PlayerLoadTM (0.54–0.68). Including d-RPE lowered Akaike Information Criterion. The slope estimate between objective and subjective measures of sleep quality was not significant. A trivial relationship (r =  0.12; CI −0.03, 0.27) was observed between objective and subjective sleep duration with subjective measures overestimating (mean bias 25 min) sleep duration (TEE 41 min). Conclusions Daily RPE offers a proxy measure of internal workload in Australian Army recruits; however, the current subjective sleep questionnaire should not be considered a proxy measure of objective sleep measures. [ABSTRACT FROM AUTHOR]

Objective: In this third communication, the processes for converting criterion occupational tasks into bona fide pre-employment selection tests are presented using urban firefighters as the worked example. Methods: A total of 14 individuals participated in potential screening tests that targeted three loaded movement categories: single-sided load carriage (4 tests), dragging loads (2 tests), and overhead pushing and holding objects (5 tests). Results: Seven tests emerged, one performed as an isolated pass/fail barrier test (ladder raise) and six incorporated into a sequential, timed circuit simulating hazmat incidents, ventilation fan carriage (stairs), motor-vehicle rescues, bushfire incidents, fire attacks, and a firefighter rescue. Conclusion: Because three tests provided predicted performance speeds to replicate the oxygen cost of firefighters performing the corresponding occupational simulations, notional performance thresholds could be projected and recommended for the final phase of this research. [ABSTRACT FROM AUTHOR]

Objective: The physiological demands of 15 essential, physically demanding fire-fighting tasks were investigated to identify criterion tasks for bona fide recruit selection. Methods: A total of 51 operational firefighters participated in discrete, field-based occupational simulations, with physiological responses measured throughout. Results: The most stressful tasks were identified and classified according to dominant fitness attributes and movement patterns. Three movement classes (single-sided load carriage [5 tasks], dragging loads [4 tasks], and overhead pushing and holding objects [2 tasks]) and one mandatory strength task emerged. Seven criterion tasks were identified. Load holding and carriage dominated these movement patterns, yet no task accentuated whole-body endurance. Conclusion: Material handling movements from each classification must appear within a physical aptitude (selection) test for it to adequately represent the breadth of tasks performed by Australian urban firefighters. [ABSTRACT FROM AUTHOR]

Quality problem or issue: Inadequate observance of basic processes in patient care such as patient monitoring and documentation practices are potential impediments to the timely diagnoses and management of patients. These gaps exist in low resource settings such as Sierra Leone and can be attributed to a myriad of factors such as workforce and technology deficiencies. Initial assessment: In the study site, only 12.4% of four critical vital signs were documented in the pre-intervention period. Choice of solution: Implement a failure mode and effects analysis (FMEA) to improve documentation of four patient vital signs: temperature, blood pressure, pulse rate and respiratory rate. Implementation: FMEA was implemented among a subpopulation of health workers who are involved in monitoring and documenting patient vital signs. Pre- and post-FMEA monitoring and documentation practice were compared with a control site. Evaluation: Participants identified a four-step process to monitoring and documenting vital signs, three categories of failure modes and four potential solutions. Based on 2100 patient days of documentation compliance data from 147 patients between July and November 2012, staff members at the study site were 1.79 times more likely to document all four patient vital signs in the postimplementation period (95% CI [1.35, 2.38]). Lessons learned: FMEA is a feasible and effective strategy for improving quality and safety in an austere medical environment. Documentation compliance improved at the intervention facility. To evaluate the scalability and sustainability of this approach, programs targeting the development of these types of process improvement skills in local staff should be evaluated. [ABSTRACT FROM AUTHOR]

The article presents a study on the multiepitope supramolecular peptide nanofibers extract coordinated with humoral and cellular anti-tumor immune responses. It highlights the potential clinical benefit of vaccine-induced antibody responses for tumor treatments. It analyzes how different combinations with checkpoint blockade further improved the efficacy of nanofiber vaccine treatment.

Purpose To identify an optimal margin about the gross target volume (GTV) for stereotactic radiosurgery (SRS) of brain metastases, minimizing toxicity and local recurrence. Methods and Materials Adult patients with 1 to 3 brain metastases less than 4 cm in greatest dimension, no previous brain radiation therapy, and Karnofsky performance status (KPS) above 70 were eligible for this institutional review board–approved trial. Individual lesions were randomized to 1- or 3- mm uniform expansion of the GTV defined on contrast-enhanced magnetic resonance imaging (MRI). The resulting planning target volume (PTV) was treated to 24, 18, or 15 Gy marginal dose for maximum PTV diameters less than 2, 2 to 2.9, and 3 to 3.9 cm, respectively, using a linear accelerator–based image-guided system. The primary endpoint was local recurrence (LR). Secondary endpoints included neurocognition Mini-Mental State Examination, Trail Making Test Parts A and B, quality of life (Functional Assessment of Cancer Therapy-Brain), radionecrosis (RN), need for salvage radiation therapy, distant failure (DF) in the brain, and overall survival (OS). Results Between February 2010 and November 2012, 49 patients with 80 brain metastases were treated. The median age was 61 years, the median KPS was 90, and the predominant histologies were non–small cell lung cancer (25 patients) and melanoma (8). Fifty-five, 19, and 6 lesions were treated to 24, 18, and 15 Gy, respectively. The PTV/GTV ratio, volume receiving 12 Gy or more, and minimum dose to PTV were significantly higher in the 3-mm group (all P <.01), and GTV was similar ( P =.76). At a median follow-up time of 32.2 months, 11 patients were alive, with median OS 10.6 months. LR was observed in only 3 lesions (2 in the 1 mm group, P =.51), with 6.7% LR 12 months after SRS. Biopsy-proven RN alone was observed in 6 lesions (5 in the 3-mm group, P =.10). The 12-month DF rate was 45.7%. Three months after SRS, no significant change in neurocognition or quality of life was observed. Conclusions SRS was well tolerated, with low rates of LR and RN in both cohorts. However, given the higher potential risk of RN with a 3-mm margin, a 1-mm GTV expansion is more appropriate. [ABSTRACT FROM AUTHOR]

Objective: Medical technology designed for Western settings frequently does not function adequately or as intended when placed in an austere clinical environment because of issues such as the instability of the electrical grid, environmental conditions, access to replacement parts, level of provider training and general absence of biomedical engineering support. The purpose of this study was to demonstrate the feasibility of applying failure mode and effects analysis as part of an implementation strategy for medical devices in austere medical settings.Design: Observational case-study. SETTING/PARTICIPANTS/INTERVENTION: We conducted failure mode and effects analysis sessions with 16 biomedical engineering technicians at two tertiary-care hospitals in Freetown, Sierra Leone. The sessions focused on maintenance and repair processes for the Universal Anaesthesia Machine. Participating biomedical engineers detailed local maintenance and repair processes and failure modes, including resource availability, communication challenges, use errors and physical access to the machine.Main Outcome Measure(s): Qualitative descriptive themes in barriers perceived and solutions generated by biomedical engineers.Results: Solutions generated involved redesigned work processes to increase the efficiency of identifying machine malfunctions, clinician engagement strategies, a formal plan for acquiring spare parts and plans for improving access to the machine. Follow-up interviews indicated solutions generated were implemented and perceived to be effective.Conclusions: This study demonstrates the feasibility of using the failure mode and effects analysis approach to improve implementation of technology in austere medical environments. [ABSTRACT FROM AUTHOR]

Objective Medical technology designed for Western settings frequently does not function adequately or as intended when placed in an austere clinical environment because of issues such as the instability of the electrical grid, environmental conditions, access to replacement parts, level of provider training and general absence of biomedical engineering support. The purpose of this study was to demonstrate the feasibility of applying failure mode and effects analysis as part of an implementation strategy for medical devices in austere medical settings. Design Observational case-study. Setting/Participants/Intervention We conducted failure mode and effects analysis sessions with 16 biomedical engineering technicians at two tertiary-care hospitals in Freetown, Sierra Leone. The sessions focused on maintenance and repair processes for the Universal Anaesthesia Machine. Participating biomedical engineers detailed local maintenance and repair processes and failure modes, including resource availability, communication challenges, use errors and physical access to the machine. Main Outcome Measure(s) Qualitative descriptive themes in barriers perceived and solutions generated by biomedical engineers. Results Solutions generated involved redesigned work processes to increase the efficiency of identifying machine malfunctions, clinician engagement strategies, a formal plan for acquiring spare parts and plans for improving access to the machine. Follow-up interviews indicated solutions generated were implemented and perceived to be effective. Conclusions This study demonstrates the feasibility of using the failure mode and effects analysis approach to improve implementation of technology in austere medical environments. [ABSTRACT FROM AUTHOR]

Background: The aim of this study was to describe the utilization patterns of brain tissue oxygen (PbtO2) monitoring following severe traumatic brain injury (TBI) and determine associations with mortality, health care use, and pulmonary toxicity. Methods: We conducted a retrospective cohort study of patients from United States trauma centers participating in the American College of Surgeons National Trauma Databank between 2008 and 2016. We examined patients with severe TBI (defined by admission Glasgow Coma Scale score ≤ 8) over the age of 18 years who survived more than 24 h from admission and required intracranial pressure (ICP) monitoring. The primary exposure was PbtO2 monitor placement. The primary outcome was hospital mortality, defined as death during the hospitalization or discharge to hospice. Secondary outcomes were examined to determine the association of PbtO2 monitoring with health care use and pulmonary toxicity and included the following: (1) intensive care unit length of stay, (2) hospital length of stay, and (3) development of acute respiratory distress syndrome (ARDS). Regression analysis was used to assess differences in outcomes between patients exposed to PbtO2 monitor placement and those without exposure by using propensity weighting to address selection bias due to the nonrandom allocation of treatment groups and patient dropout. Results: A total of 35,501 patients underwent placement of an ICP monitor. There were 1,346 (3.8%) patients who also underwent PbtO2 monitor placement, with significant variation regarding calendar year and hospital. Patients who underwent placement of a PbtO2 monitor had a crude in-hospital mortality of 31.1%, compared with 33.5% in patients who only underwent placement of an ICP monitor (adjusted risk ratio 0.84, 95% confidence interval 0.76–0.93). The development of the ARDS was comparable between patients who underwent placement of a PbtO2 monitor and patients who only underwent placement of an ICP monitor (9.2% vs. 9.8%, adjusted risk ratio 0.89, 95% confidence interval 0.73–1.09). Conclusions: PbtO2 monitor utilization varied widely throughout the study period by calendar year and hospital. PbtO2 monitoring in addition to ICP monitoring, compared with ICP monitoring alone, was associated with a decreased in-hospital mortality, a longer length of stay, and a similar risk of ARDS. These findings provide further guidance for clinicians caring for patients with severe TBI while awaiting completion of further randomized controlled trials. [ABSTRACT FROM AUTHOR]

High-speed running (HSR) loads have been linked with non-contact injury risks in team-sports. This study investigated whether player-specific speed zones, reflecting individual fitness characteristics, impact the associations between non-contact injury and acute and chronic HSR loads. Semi-professional soccer players from two clubs (n = 47) were tracked over two seasons using 10 Hz GPS (5552 observations). HSR distances were calculated arbitrarily (≥5.5 m·s−1), and in an individualised fashion based on the final speed of the 30–15 intermittent fitness test. Cumulative running loads were represented by exponentially weighted moving averages with 7-(acute) and 28-day (chronic) decay parameters. Physiotherapists collected non-contact, lower-limb, time-loss injury data (n = 101). Injury models using session type (training vs matches), coach, as well as arbitrary or individualised running loads were constructed via mixed-effect logistic regression. Session type had the largest effect on injury (training vs match OR = 0.28; 95%CI:0.17–0.44). Variations in individualised or arbitrary acute and chronic HSR loads within the mid-range of the observed data had negligible effects on predicted injury risk. However, the uncertainty of estimated effects at extreme values of acute and chronic HSR loads prevented any conclusive findings. Therefore, the efficacy of using customised speed thresholds in quantifying load for injury risk mitigation purposes remains unclear. [ABSTRACT FROM AUTHOR]

Background: Early hypotension following moderate to severe traumatic brain injury (TBI) is associated with increased mortality and poor long-term outcomes. Current guidelines suggest the use of intravenous vasopressors to support blood pressure following TBI; however, guidelines do not specify vasopressor type, resulting in variation in clinical practice. Minimal data are available to guide clinicians on optimal early vasopressor choice to support blood pressure following TBI. Therefore, we conducted a multicenter study to examine initial vasopressor choice for the support of blood pressure following TBI and its association with clinical and functional outcomes after injury. Methods: We conducted a retrospective cohort study of patients enrolled in the transforming research and clinical knowledge in traumatic brain injury (TRACK-TBI) study, an 18-center prospective cohort study of patients with TBI evaluated in participating level I trauma centers. We examined adults with moderate to severe TBI (defined as Glasgow Coma Scale score < 13) who were admitted to the intensive care unit and received an intravenous vasopressor within 48 h of admission. The primary exposure was initial vasopressor choice (phenylephrine versus norepinephrine), and the primary outcome was 6-month Glasgow Outcomes Scale Extended (GOSE), with the following secondary outcomes: length of hospital stay, length of intensive care unit stay, in-hospital mortality, new requirement for dialysis, and 6-month Disability Rating Scale. Regression analysis was used to assess differences in outcomes between patients exposed to norepinephrine versus phenylephrine, with propensity weighting to address selection bias due to the nonrandom allocation of the treatment groups and patient dropout. Results: The final study sample included 156 patients, of whom 79 (51%) received norepinephrine, 69 (44%) received phenylephrine, and 8 (5%) received an alternate drug as their initial vasopressor. 121 (77%) of patients were men, with a mean age of 43.1 years. Of patients receiving norepinephrine as their initial vasopressor, 32% had a favorable outcome (GOSE 5–8), whereas 40% of patients receiving phenylephrine as their initial vasopressor had a favorable outcome. Compared with phenylephrine, exposure to norepinephrine was not significantly associated with improved 6-month GOSE (weighted odds ratio 1.40, 95% confidence interval 0.66–2.96, p = 0.37) or any secondary outcome. Conclusions: The majority of patients with moderate to severe TBI received either phenylephrine or norepinephrine as first-line agents for blood pressure support following brain injury. Initial choice of norepinephrine, compared with phenylephrine, was not associated with improved clinical or functional outcomes. [ABSTRACT FROM AUTHOR]

Military personnel are required to complete physically demanding tasks when performing work and training, which may be quantified through the physical stress imposed (external load) or the resultant physiological strain (internal load). The aim of this narrative review is to provide an overview of the techniques used to monitor work and training load in military settings, summarise key findings, and discuss important practical, analytical, and conceptual considerations. Most investigations have focused upon measuring external and internal load in military training environments; however, limited data exist in operational settings. Accelerometry has been the primary tool used to estimate external load, with heart rate commonly used to quantify internal load. Supplemental to heart rate, psychophysiological and biochemical measures have also been investigated to elucidate aspects of internal load. Broadly, investigations have revealed that military training requires personnel to perform relatively large volumes of physical activity (e.g. averaging ∼15,000 steps·day−1) of typically low-moderate intensity activity (<6 MET), although considerable temporal and inter-individual variability is observed from these gross mean estimates. There are limitations associated with these measures and, at best, estimates of external and internal load can only be inferred. These limitations are particularly pertinent for military tasks such as load carriage and manual material handling, which often involve complex activities performed individually or in teams, in a range of operational environments, with multiple layers of protection, over a protracted duration. Comprehensively quantifying external and internal loads during these functional activities poses substantial practical and analytical challenges. [ABSTRACT FROM AUTHOR]

Purpose: Patients with recurrent malignant gliomas treated with stereotactic radiosurgery (SRS) and multiagent systemic therapies were reviewed to determine the effects of patient- and treatment-related factors on survival and toxicity. Methods and Materials: A retrospective analysis was performed on patients with recurrent malignant gliomas treated with salvage SRS from September 2002 to March 2010. All patients had experienced progression after treatment with temozolomide and radiotherapy. Salvage SRS was typically administered only after multiple postchemoradiation salvage systemic therapies had failed. Results: 63 patients were treated with SRS for recurrent high-grade glioma; 49 patients had World Health Organization (WHO) Grade 4 disease. Median follow-up was 31 months from primary diagnosis and 7 months from SRS. Median overall survival from primary diagnosis was 41 months for all patients. Median progression-free survival (PFS) and overall survival from SRS (OS-SRS) were 6 and 10 months for all patients, respectively. The 1-year OS-SRS for patients with Grade 4 glioma who received adjuvant (concurrent with or after SRS) bevacizumab was 50% vs. 22% for patients not receiving adjuvant bevacizumab (p = 0.005). Median PFS for patients with a WHO Grade 4 glioma who received adjuvant bevacizumab was 5.2 months vs. 2.1 months for patients who did not receive adjuvant bevacizumab (p = 0.014). Karnofsky performance status (KPS) and age were not significantly different between treatment groups. Treatment-related Grade 3/4 toxicity for patients receiving and not receiving adjuvant BVZ was 10% and 14%, respectively (p = 0.58).On multivariate analysis, the relative risk of death and progression with adjuvant bevacizumab was 0.37 (confidence interval [CI] 0.17–0.82) and 0.45 (CI 0.21–0.97). KPS >70 and age <50 years were significantly associated with improved survival. Conclusions: The combination of salvage radiosurgery and bevacizumab to treat recurrent malignant gliomas is well tolerated and seems to be associated with improved outcomes. Prospective multiinstitutional studies are required to determine efficacy and long-term toxicity with this approach. [ABSTRACT FROM AUTHOR]

Purpose: To describe our experience and clinical strategy for stereotactic body radiotherapy (SBRT) of spinal lesions. Methods and Materials: Thirty-two patients with 33 spinal lesions underwent computed tomography–based simulation while free breathing. Gross/clinical target volumes included involved portions of the vertebral body and paravertebral/epidural tumor. Planning target volume (PTV) expansion was 6 mm axially and 3 mm radially; the cord was excluded from the PTV. Biologic equivalent dose was calculated using the linear quadratic model with α/β = 3 Gy. Treatment was linear accelerator based with on-board imaging; dose was adjusted to maintain cord dose within tolerance. Survival, local control, pain, and neurologic status were monitored. Results: Twenty-one patients are alive at 1 year (median survival, 14 months). Median follow-up is 6 months for all patients (7 months for survivors). Mean previous radiotherapy dose to 22 patients was 35 Gy, and median interval was 17 months. Renal (31%), breast, and lung (19% each) were the most common histologic sites. Three SBRT fractions (range, one to four fractions) of 7 Gy (range, 5–16 Gy) were delivered. Median cord and target biologic equivalent doses were 70 Gy3 and 34.3 Gy10, respectively. Thirteen patients reported complete and 17 patients reported partial pain relief at 1 month. There were four failures (mean, 5.8 months) with magnetic resonance imaging evidence of in-field progression. No dosimetric parameters predictive of failure were identified. No treatment-related toxicity was seen. Conclusions: Spinal SBRT is effective in the palliative/re-treatment setting. Volume expansion must ensure optimal PTV coverage while avoiding spinal cord toxicity. The long-term safety of spinal SBRT and the applicability of the linear-quadratic model in this setting remain to be determined, particularly the time-adjusted impact of prior radiotherapy. [Copyright &y& Elsevier]