Development of a platform-based approach for the clinical production of HIV gp120 envelope glycoprotein vaccine candidates

Preclinical development of vaccine candidates is an important link between the discovery and manufacture of vaccines for use in human clinical trials. Here, an exploratory clinical study utilizing multiple gp120 envelope proteins as vaccine antigens was pursued, which required a harmonized platform development approach for timely and efficient manufacture of the combined HIV vaccine product.Development of cell lines, processes, and analytical methods was initiated with a transmitted founder envelope protein (CH505TF), then applied to produce three subsequent gp120 Env (envelope) variants. Cell lines were developed using the commercially available Freedom CHO DG44 kit (Life Technologies). The fed-batch cell culture production process was based on a commercially-available medium with harmonized process parameters across the variants. A platform purification process was developed utilizing a mixed mode chromatography capture step, with ceramic hydroxyapatite and ion exchange polishing steps. A suite of analytical methods was developed to establish and monitor the Quality Target Profile (QTP), release and long-term stability testing of the vaccine products.The platform development strategy was successfully implemented to produce four gp120 envelope protein variants. In some cases, minor changes to the platform were required to optimize for a particular variant; however, baseline conditions for the processes (cell line type, media & feed system, chromatography resins, and analytical approaches) remained constant, leading to successful transfer and manufacture of all four proteins in a cGMP facility.This body of work demonstrates successful pursuit of a platform development approach to manufacture important vaccine candidates and can be used as a model for other vaccine glycoproteins, such as HIV gp140 trimers or other viral glycoproteins with global health implications.Clinical trial identifier.NCT03220724, NCT03856996.     

Tuber-to-Anterior Process Angle (TAPA): A cadaveric study and surgical technique for placing axial calcaneal screws

We describe results of a cadaveric study and an accompanying surgical technique which simplifies posterior-to-anterior axial screw placement into the calcaneus, often utilized during fixation of displaced intra-articular calcaneus fractures or calcaneal osteotomies. By defining the Tuber-to-Anterior Process Angle (TAPA), this technique facilitates axial screw placement, thereby decreasing reliance on intraoperative fluoroscopy and reducing operative time.     

Impaired Theory of Mind and psychosocial functioning among pediatric patients with Type I versus Type II bipolar disorder

Deficits in Theory of Mind (ToM) have been documented among pediatric patients with Bipolar Disorder (BD). However, fewer studies have directly examined differences between type I and type II patients and whether or not ToM deficits are related to psychosocial difficulties. Therefore, the aim of this study was to compare type I versus type II pediatric bipolar patients and matched Healthy Controls (HC) on ToM and interpersonal functioning tasks. All participants completed the Revised Mind in the Eyes Task (MET), the Cognitive and Emotional Perspective Taking Task (CEPTT), and the Index of Peer Relations (IPR). Type I BD patients reported greater peer difficulties on the IPR compared to HC, and also performed more poorly on the MET and the cognitive condition of the CEPTT, but did not differ significantly on the emotional condition. There were no significant group differences between type II BD patients and HC. More impaired ToM performance was associated with poorer interpersonal functioning. Type I BD patients show deficits in the ability to understand another's mental state, irrespective of emotional valence. Deficits in understanding others' mental states could be an important treatment target for type I pediatric patients with BD.     

Intention to quit water pipe smoking among Arab Americans: Application of the theory of planned behavior

In this study, we examined the effect of theory of planned behavior (TPB) constructs on the intention to quit water pipe smoking by using an observational, survey-based, cross-sectional study design with a convenient sample of Arab American adults in Houston, Texas. Multivariate logistic regression models were used to determine predictors of intention to quit water pipe smoking in the next year. A total of 340 participants completed the survey. Behavioral evaluation, normative beliefs, and motivation to comply were significant predictors of an intention to quit water pipe smoking adjusting for age, gender, income, marital status, and education. Interventions and strategies that include these constructs will assist water pipe smokers in quitting.     

Social cognitive correlates of device-measured and self-reported physical activity in Black and White individuals with multiple sclerosis

BackgroundThere is increasing research interest regarding physical activity behavior among persons with multiple sclerosis (MS), yet there is little known about physical activity and its correlates in Black persons with MS.ObjectiveThis cross-sectional study assessed associations among social cognitive theory (SCT) variables and device-measured and self-reported physical activity in samples of Black and White persons with MS.MethodsParticipants included 67 Black and 141 White persons with MS who wore an ActiGraph accelerometer on a belt around the waist measuring moderate-to-vigorous physical activity (MVPA) for seven days and completed a battery of questionnaires. Questionnaires included demographic and clinical characteristics, leisure-time exercise, exercise self-efficacy, overcoming barriers self-efficacy, function, social support, exercise outcome expectations, and goal setting and planning.ResultsBlack participants with MS engaged in significantly less MVPA, but not sedentary behavior or light physical activity, than the White participants with MS. Black participants further had significantly lower levels of exercise self-efficacy and outcome expectations than the White sample. All SCT correlates were significantly correlated with self-reported physical activity, but only exercise and barriers self-efficacy, perceived function, and exercise goal setting were associated with device-measured MVPA. The difference in physical activity between Black and White participants with MS was accounted for by differences in exercise self-efficacy and outcome expectations.ConclusionsResearchers should consider developing behavioral interventions that target exercise self-efficacy and outcome expectations as SCT variables for increasing physical activity in Black persons with MS.     

Chondrocytes from Different Zones Exhibit Characteristic Differences in High Density Culture

Superficial and middle/deep zone chondrocytes were isolated from goat femoral cartilage by a zonal abrasion method. The cells were expanded 100-fold through two passages, then seeded into agarose wells to form high-density constructs through a self-assembling process. After 4 weeks in culture, the superficial zone constructs contracted into a dense cell mass, while middle/deep zone chondrocytes formed constructs with four distinct regions. Middle/deep zone chondrocytes produced 250% more glycosaminoglycans per dry weight and more collagen per dry weight than superficial zone chondrocytes. The superficial and middle/deep zone chondrocytes were found to retain characteristic differences even after 100-fold expansion, as evidenced by construct morphology and extracellular matrix content. This study uniquely demonstrated the ability of expanded superficial and middle/deep zone chondrocytes to form constructs of distinct characteristics without a scaffold. The goal of tissue engineering different zones of cartilage is to eventually replicate the specific function of each zone.     

Reliability and Construct Validity of the Malay Version of Theory of Planned Behaviour (TPB) for Smoking Cessation

Objective: The aim of this study was to evaluate the psychometric properties of the Malay translated version ofthe Theory of Planned Behavior (TPB) intention to quit smoking questionnaire. Methods: A cross-sectional studywas performed involving 185 male smokers. The forward-backward translation procedure was adopted to translate thequestionnaire from English to Malay. The internal consistency and stability were assessed using Cronbach’s alpha and acorrelation analysis and Exploratory Factor Analysis was conducted. Result: The translated questionnaire showed goodinternal consistency with Cronbach’s alpha values of 0.86, 0.64, 0.74 and 0.90 for each of the four respective factors.The test-retest reliability revealed acceptable stability, with Spearman’s correlation coefficients ranging from low tomoderate (r>0.30-0.50) and a satisfactory inter class correlation coefficient (ICCs). The construct validity achieved anacceptable factor loading for each construct which ranged from 0.40 to 0.90. Conclusion: The current study providedpsychometric evidence for an appropriate, reliable and valid tool of TPB Malay version. This questionnaire could beapplied in evaluating smoking cessation interventions in Malaysia.     

江海交汇处区域经济空间结构的重构

运用克里斯塔勒中心地理论和引力模型等分析方法，以长江与南黄海交汇处的南通市为例，分析了以淤泥质海岸为主体江海交会处区域经济空间结构及内部差异形成的要素，以及此类地区沿海区域经济社会发展滞后的动力机制。论证了新一轮沿海开发和空间结构重构中，该类地区以沿江沿路经济轴带为基础，实施陆海统筹、江海陆协同发展的必然性。提出要充分利用原有基础，在不同区域利用各自优势，因地制宜实施发展战略，打造区域经济空间网络结构，实现区域空间均衡发展。力图从一个侧面探讨大的江河与淤泥质海岸交汇处区域发展问题的研究范式。     

The impact of bilateral cerebellar damage on theory of mind,empathy and decision making

The extensive infarction affecting the posterior vermis and the medial and posterior regions of both cerebellar hemispheres, as well as the small central pontine lesion, seems to have disrupted multiple cerebral and brainstem cerebellar loops. These loops process information related to many cognitive domains, behavior and emotion, including decision making, empathy and theory of mind.