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Modern photogrammetry and remote sensing have found small Unmanned Aerial Vehicles (UAVs) to be a valuable source of data in various branches of science and industry (e.g., agriculture, cultural heritage). Recently, the growing role of laser scanning in the application of UAVs has also been observed. Laser scanners dedicated to UAVs consist of four basic components: a laser scanner (LiDAR), an Inertial Measurement Unit (IMU), a Global Navigation Satellite System (GNSS) receiver and an on-board computer. The producers of the system provide users with detailed descriptions of the accuracies separately for each component. However, the final measurement accuracy is not given. This paper reviews state-of-the-art of laser scanners developed specifically for use on a UAV, presenting an overview of several constructions that are available nowadays. The second part of the paper is focussed on analysing the influence of the sensor accuracies on the final measurement accuracy. Mathematical models developed for Airborne Laser Scanning (ALS) accuracy analyses are used to estimate the theoretical accuracies of different scanners with conditions typical for UAV missions. Finally, the theoretical results derived from the mathematical simulations are compared with an experimental use case.

This paper presents the possibilities for using an unmanned aerial system for evaluation of the condition of levees. The unmanned aerial system is equipped with two types of sensor. One is an ultra-light laser scanner, integrated with a GNSS receiver and an INS system; the other sensor is a digital camera that acquires data with stereoscopic coverage. Sensors have been mounted on the multirotor, unmanned platform the Hawk Moth, constructed by MSP company. LiDAR data and images of levees the length of several hundred metres were acquired during testing of the platform. Flights were performed in several variants. Control points measured with the use of the GNSS technique were considered as reference data. The obtained results are presented in this paper; the methodology of processing the acquired LiDAR data, which increase in accuracy when low accuracy of the navigation systems occurs as a result of systematic errors, is also discussed. The Iterative Closest Point (ICP) algorithm, as well as measurements of control points, were used to georeference the LiDAR data. Final accuracy in the order of centimetres was obtained for generation of the digital terrain model. The final products of the proposed UAV data processing are digital elevation models, an orthophotomap and colour point clouds. The authors conclude that such a platform offers wide possibilities for low-budget flights to deliver the data, which may compete with typical direct surveying measurements performed during monitoring of such objects. However, the biggest advantage is the density and continuity of data, which allows for detection of changes in objects being monitored.

Purpose. The article presents problem of the influence of local inhomogeneities of ground on the internal forces in the steel pipe. Methodology. The authors presented the differences in the distributions of earth pressures for the pipes. One of the most common methods is the microtunneling technology. The examples of numerical analysis by finite element method (FEM) have been calculated. Findings. The results of numerical analysis are presented for selected ground conditions and the distribution of internal forces in the flexible section of the steel pipe is also shown. Originality and Practical value. The obtained results clearly show the influence of flexural rigidity of the pipe on the internal forces, the influence of flexural rigidity and the soil stiffness on the size of the bending moments in the steel of pipe jacking. They depend on the interaction of soil – steel pipe.

The study involved 50 insemination boars at the age of 8–9 months at the beginning of the study. Each boar was assessed four times for its sexual activity: at the beginning of breeding service and after three, six and nine months into the insemination service. Ejaculates were collected for the purpose of the sexual activity parameters’ assessment. Physical parameters of the ejaculates were subsequently analysed. Pearson’s linear correlation was used to calculate the coefficients of a phenotypic correlation between sexual activity levels and physical parameters of the ejaculates. According to this an appropriate analysis was conducted concerning the changes in boars’ sexual activity throughout their dynamic, sexual development. It was proved, that ejaculate volume depends on the total time of copulation. The highest correlation between ejaculate volume and sexual urge levels was observed in the youngest boars at the beginning of insemination service. The correlation between the ejaculatory efficiency and a boar’s libido changes with age and sexual development. Changes in ejaculatory efficiency are the most dynamic at the age of approx. 1.5 years. At this age ejaculate volume and ejaculate sperm count dynamically increase. The insemination fitness forecasting in case of boars should include libido measurements taken at the beginning of an insemination service – within the first three months. Measurements taken at a more advanced age are of little use for the purpose of ejaculatory efficiency forecasting in case of boars.

Background: War and forced migration expose refugees to trauma and ongoing stress, often contributing to long-term psychological consequences. Typically, trauma exposure is assessed cumulatively; yet, trauma type may better predict psychological outcomes. This study examined the differential impact of cumulative trauma and trauma subtypes (victimization, death threat, accidental/injury) on postmigration trajectories of posttraumatic stress and anxiety in refugees., Method: Seventy-seven Syrian (88.3%) and Iraqi (9.1%) adult refugees self-reported prior trauma exposure and psychological symptoms at time of arrival in the United States and 2 years post. Linear mixed-effects modeling was performed to assess for associations between trauma variables and symptom trajectories. Models using cumulative trauma as a predictor were compared to models including the three trauma subtype variables as predictors, using pseudo- R ² values to compare variance explained between the two methods of trauma measurement., Results: Linear mixed-effects modeling indicated that prior exposure to victimization predicted progressively worsening posttraumatic stress disorder (PTSD) symptoms over time postmigration ( b = .97, SE = .45, t = 2.14, p = .036). Cumulative trauma also predicted increasing PTSD symptoms ( b = .124, SE = .06, t = 2.09, p = .041), but explained less variance than victimization (9% vs. 18.1%). Direct effects of cumulative trauma ( p = .009) and victimization ( p = .002) on anxiety severity emerged; however, anxiety symptoms did not change over time depending on prior trauma exposure. Accidents/injuries and death threats did not predict PTSD or anxiety., Conclusions: These findings can be leveraged toward focused identification of those at highest risk for progressive illness postmigration, thus providing empirical guidance for allocation of interventions and resources for refugees. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Background: Fear- and trauma-related conditions, such as post-traumatic stress disorder (PTSD) and social phobia, often manifest as socially avoidant behaviours, which commonly contribute to social and occupational disability transdiagnostically. While gold-standard treatments (i.e. exposure therapy, psychotropic medications) are effective, they are hindered by high dropout rates and limited impact on real-world functioning. Furthermore, most existing interventions only target symptom reduction, with few addressing avoidance-related deficits in social and occupational functioning. Objectives: This methods paper introduces an innovative augmented reality exposure therapy (ARET) technology designed to address the limitations of traditional interventions for anxiety disorders and PTSD, by directly targeting social and occupational dysfunction through exposure to real-life social contexts. Method: We introduce an ARET system, using artificial intelligence (AI)-driven, augmented reality (AR) technology, that enables exposure to realistic scenarios within the patient's real-world environment, fostering contextual generalization and functional improvement. Featuring holographic three-dimensional humans, precise surface mapping, wireless mobility, and telemedicine capabilities, the software provides customizable exposure scenarios to transform an environment into various spaces (e.g. grocery store, house party) with diverse human characters, as well as flexible AI-driven human interactions tailored to individual needs. Results: We share observations and feedback from the treatment of first responders with PTSD. Patients found the technology easy to use, with immersive realism, active engagement, and strong emotional responses needed for effective exposure therapy. Advances in AI-driven character development and AR hardware accessibility support the wider adoption of ARET by clinicians. Conclusion: By bridging the gap between clinical interventions and real-world functioning, ARET offers a transformative approach to addressing the pervasive impact of psychiatric disorders on social and occupational outcomes.

Objective: Trauma exposure-a contributor to psychological risk for refugee youth-is typically assessed using cumulative indices; however, recent findings indicate that trauma type may better predict psychological outcomes. This study investigated the utility of two methods of classifying trauma exposure-cumulative trauma and exposure to specific types of trauma (i.e., trauma subtypes)-in predicting the severity of symptoms related to posttraumatic stress disorder (PTSD) and anxiety for refugee youth., Method: 96 Syrian and Iraqi youth resettled as refugees in the United States self-reported trauma exposure and psychological symptoms. Multiple regression was used to assess the variance in symptom severity explained by specific trauma subtypes (i.e., victimization, death threat, and accidental/injury) as compared to cumulative trauma scores., Results: Multiple regression models predicting PTSD revealed cumulative trauma ( b = 0.07; p = .004) and death threat trauma ( b = 0.16; p = .001) as significant predictors of PTSD symptom severity; notably, death threat trauma was the only subtype associated with PTSD and explained more variance than cumulative trauma scores (10.3% and 8.4%, respectively). Cumulative trauma, but no specific trauma subtype, was associated with anxiety ( b = .03; p = .043); however, this relation did not survive correction for multiple comparisons., Conclusion: Focused trauma assessment-particularly consideration of death threat trauma and cumulative trauma exposures-may be useful in evaluating the risk of PTSD symptoms in refugee youth, whereas symptoms related to anxiety may be driven by other factors. These findings can be leveraged toward focused identification of youth at highest risk for PTSD symptoms, to improve prevention and early intervention efforts. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Background: War and natural disasters lead to forced migration - and increased risk of adverse psychological outcomes - in approximately 1% of the global population. Though recent years have brought a greater understanding of the consequences of war exposure on mental health outcomes for refugee children, little is known about the longitudinal and developmental impact of these experiences on youth., Aims: The aim of this study was to assess the effect of direct exposure to war and/or combat on trajectories of symptoms related to anxiety and post-traumatic stress disorder (PTSD) in Syrian and Iraqi refugee youth following resettlement. Prevalence of possible anxiety disorders and PTSD was also assessed., Method: Participants included accompanied refugee youth resettled in the state of Michigan in the U.S. ( n  = 74). Youth filled out self-report measures of trauma exposure, anxiety symptoms, and PTSD symptoms upon arrival and 2 years later. Linear mixed-effects modeling was used to assess the effect of war exposure over time., Results: Upon arrival, 38% screened positive for an anxiety disorder and 4.1% met diagnostic thresholds for PTSD. While war exposure did not predict changes to PTSD symptom trajectories ( p  = .481), anxiety symptoms increased over time among children reporting war exposure ( B  = 10.13, SE  = 4.22, t  = 2.40, p  = .019)., Conclusions: Our findings suggest that without appropriate interventions, anxiety- and trauma-related symptoms often do not decrease. Further, exposure to war trauma may lead to progressive worsening of symptoms. These findings suggest that assessing for type of trauma exposure, rather than focusing solely on migration status, may inform focused attention and interventions among trauma-exposed children resettling as refugees., Competing Interests: Conflict of interestThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

The involvement of mitochondrial dysfunction in cystatin B (CSTB) deficiency has been suggested, but its role in the onset of neurodegeneration, myoclonus, and ataxia in the CSTB-deficient mouse model ( Cstb -/- ) is yet unknown. CSTB is an inhibitor of lysosomal and nuclear cysteine cathepsins. In humans, partial loss-of-function mutations cause the progressive myoclonus epilepsy neurodegenerative disorder, EPM1. Here we applied proteome analysis and respirometry on cerebellar synaptosomes from early symptomatic ( Cstb -/- ) mice to identify the molecular mechanisms involved in the onset of CSTB-deficiency associated neural pathogenesis. Proteome analysis showed that CSTB deficiency is associated with differential expression of mitochondrial and synaptic proteins, and respirometry revealed a progressive impairment in mitochondrial function coinciding with the onset of myoclonus and neurodegeneration in ( Cstb -/- ) mice. This mitochondrial dysfunction was not associated with alterations in mitochondrial DNA copy number or membrane ultrastructure. Collectively, our results show that CSTB deficiency generates a defect in synaptic mitochondrial bioenergetics that coincides with the onset and progression of the clinical phenotypes, and thus is likely a contributor to the pathogenesis of EPM1., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Gorski, Jackson, Nyman, Rezov, Battersby and Lehesjoki.)

Pre-migration trauma, a psychological risk factor for refugees, is often measured using cumulative indices. However, recent research suggests that trauma subtypes, rather than cumulative trauma, may better predict psychological outcomes. This study investigated the predictive utility of trauma subtypes in the assessment of refugee mental health. Multiple regression was used to determine whether cumulative trauma or trauma subtypes explained more variance in depression, anxiety, and post-traumatic stress disorder (PTSD) symptom scores in 70 Syrian and Iraqi refugees. Subtype models performed better than cumulative trauma models for PTSD (cumulative R 2  = 0.138; subtype R 2  = 0.32), anxiety (cumulative R 2  = 0.061; subtype R 2  = 0.246), and depression (cumulative R 2  = 0.041; subtype R 2  = 0.184). Victimization was the only subtype significantly associated with PTSD (p < 0.001; r 2  = 0.210), anxiety (p < 0.001; r 2  = 0.162), and depression (p = 0.002; r 2  = 0.140). Cumulative trauma was predictive of PTSD symptoms only (p = 0.003; r 2  = 0.125). Trauma subtypes were more informative than cumulative trauma, indicating their utility for improving predictive efforts in research and clinical contexts., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Sebaceous glandular hyperplasia (SGH) is a benign form of skin pathology, occurring in approximately one percent of the population. Risk factors for the SGH include advanced age, male sex, exposure to UV radiation and immunosuppression. The pathogenesis of SGH involves hormonal changes, is also regulated by insulin levels, thyroid stimulating hormone (TSH) and cortisol. SGH manifests itself as solitary or multiple light-yellow lumps, 2-3 mm big, with a smooth surface and a central umbilical depression. The vulvar localization of lesions is extremely rare and presents with a polymorphous clinical picture, posing a major diagnostic problem. A 40-year-old patient presented to the clinic due to vulvar skin lesions, periodically with the swelling of the labia and itching, with the symptoms deteriorating for approximately two years. The patient has been consulted by several doctors; however, the diagnosis has not been established. She did not receive adequate treatment either. On physical examination, attention was drawn to the overgrown labia minora - especially on the right side - with a network of abnormal vessels and numerous small papular lesions. SGH was diagnosed, based on the samples collected from the vulva. The patient was recommended isotretinoin therapy and referred to a dermatologist for a consultation. The presented case of vulvar SGH is interesting and rare. It is a diagnostic challenge with no established treatment standards. Nonetheless, SGH should be considered in the differential diagnosis of vulvar skin lesions. The comprehensive and interdisciplinary care is needed to help patients struggling with this insidious condition.

Progressive myoclonus epilepsy of Unverricht-Lundborg type (EPM1) is a neurodegenerative disorder caused by loss-of-function mutations in the cystatin B ( CSTB ) gene. Progression of the clinical symptoms in EPM1 patients, including stimulus-sensitive myoclonus, tonic-clonic seizures, and ataxia, are well described. However, the cellular dysfunction during the presymptomatic phase that precedes the disease onset is not understood. CSTB deficiency leads to alterations in GABAergic signaling, and causes early neuroinflammation followed by progressive neurodegeneration in brains of a mouse model, manifesting as progressive myoclonus and ataxia. Here, we report the first proteome atlas from cerebellar synaptosomes of presymptomatic Cstb -deficient mice, and propose that early mitochondrial dysfunction is important to the pathogenesis of altered synaptic function in EPM1. A decreased sodium- and chloride dependent GABA transporter 1 (GAT-1) abundance was noted in synaptosomes with CSTB deficiency, but no functional difference was seen between the two genotypes in electrophysiological experiments with pharmacological block of GAT-1. Collectively, our findings provide novel insights into the early onset and pathogenesis of CSTB deficiency, and reveal greater complexity to the molecular pathogenesis of EPM1., (Copyright © 2020 Gorski, Spoljaric, Nyman, Kaila, Battersby and Lehesjoki.)

Pontocerebellar hypoplasia type 6 (PCH6) is a rare infantile-onset progressive encephalopathy caused by biallelic mutations in RARS2 that encodes the mitochondrial arginine-tRNA synthetase enzyme (mtArgRS). The clinical presentation overlaps that of PEHO syndrome (Progressive Encephalopathy with edema, Hypsarrhythmia and Optic atrophy). The proband presented with severe intellectual disability, epilepsy with varying seizure types, optic atrophy, axial hypotonia, acquired microcephaly, dysmorphic features and progressive cerebral and cerebellar atrophy and delayed myelination on MRI. The presentation had resemblance to PEHO syndrome but sequencing of ZNHIT3 did not identify pathogenic variants. Subsequent whole genome sequencing revealed novel compound heterozygous variants in RARS2, a missense variant affecting a highly conserved amino acid and a frameshift variant with consequent degradation of the transcript resulting in decreased mtArgRS protein level confirming the diagnosis of PCH6. Features distinguishing the proband's phenotype from PEHO syndrome were later appearance of hypotonia and elevated lactate levels in blood and cerebrospinal fluid. On MRI the proband presented with more severe supratentorial atrophy and lesser degree of abnormal myelination than PEHO syndrome patients. The study highlights the challenges in clinical diagnosis of patients with neonatal and early infantile encephalopathies with overlapping clinical features and brain MRI findings., (Copyright © 2019 Elsevier Masson SAS. All rights reserved.)

In this study, we tested the hypothesis that modulation of endogenous gonadotropin-releasing hormone (Gnrh) neuronal network activity alters the mRNA expression of nuclear receptor subfamily 5 group A member 1 (Nr5a1), through one of the component of Wnt pathway signaling - catenin beta 1 (Ctnnb1) (its co-activator), and its co-repressor nuclear receptor subfamily 0, group B member 1 (Nr0b1) in the female rat pituitary gland in vivo. Adult ovariectomized rats were given a serial infusion of Gnrh, kisspeptin-10, Gnrh + Gnrh antagonist (Antide), or kisspeptin-10 + kisspeptin antagonist (kisspeptin-234) into the third ventricle of the brain. The anterior pituitary and blood was used to mRNA and protein expression analysis. We demonstrated that Gnrh up-regulates Nr5a1 mRNA expression in the anterior pituitary and induces NR5A1 depletion in gonadotropes. Gnrh administration increased both Ctnnb1 mRNA expression and protein synthesis, and induced activation of cellular Ctnnb1 via translocation from the gonadotropes cytoplasm to nucleus. After kisspeptin-10 treatment, up-regulation of Nr0b1 mRNA and protein expression in the anterior pituitary was observed. These data indicate that Gnrh-neuron-mediated network activity alters Nr5a1 gene transcription and translation in gonadotrope cells and this effect may result from the changes induced in the Ctnnb1 and Nr0b1 gene/protein expression balance.

The molecular mechanism that regulates iron homeostasis is based on a network of signals, which reflect on the iron requirements of the body. Hereditary hemochromatosis is a heterogenic metabolic syndrome which is due to unchecked transfer of iron into the bloodstream and its toxic effects on parenchymatous organs. It is caused by the mutation of genes that encode proteins that help hepcidin to monitor serum iron. These proteins include the human hemochromatosis protein -HFE, transferrin-receptor 2, hemojuvelin in rare instances, and ferroportin. HFE-related hemochromatosis is the most frequent form of the disease. Interestingly, the low penetrance of polymorphic HFE genes results in rare clinical presentation of the disease, predominantly in middle-aged males. Taking into account the wide dispersion of HFE mutation in our population and also its unknown role in heterozygotes, we analyzed the impact of H63D HFE carriage in the developmental age, with respect to gender, on the iron status and hemoglobin concentration of carriers in comparison to those of wild-type HFE gene (12.7 ± 3.07 years, 42 boys and 41 girls). H63D carriers presented higher blood iron, transferrin saturation, and ferritin concentration than wild-type probands (p < 0.05.) Interestingly, male H63D carriers showed higher hemoglobin concentration than the unburdened children. Moreover, in the H63D carrier group, a positive correlation between iron and hemoglobin was noted. In conclusion, this study demonstrates that changes in iron metabolism occur at a young age in HFE heterozygotes., Competing Interests: The authors declare that they have no conflict of interest.

The well-recognized sensitivity of the galanin gene in the anterior pituitary gland to estrogen suggests that estrogen receptor activity may influence the galaninergic system through modulation of galanin receptor (GALR) gene expression. Here, we evaluated the following: (i) the effects of estrogen on GALR mRNA expression; (ii) the estrogen receptor subtype that is specifically involved in this activity; and (iii) the effects of progesterone in the absence or presence of estrogen on galanin concentration in anterior pituitary gland. In the first experiment, ovariectomized 4-month-old rats were pre-treated subcutaneously with 17β-estradiol (3 x 20 μg), the ESR1 (ERα) agonist propyl pyrazole triol (PPT) (3 x 5 mg), and the ESR2 (ERβ) agonist diarylpropionitrile (DPN) (3 x 0.5 mg). In the second experiment, 4-month-old ovariectomized females received daily subcutaneous injections of 17β-estradiol (3 x 20 μg), progesterone (2 x 5 mg), or combined estradiol (3 x 20 μg) and progesterone (2 x 5 mg). Anterior pituitaries were excised the day after the final 17β-estradiol injection (experiment I) and 1 hour after receiving the second progesterone dose. Relative GALR1, GALR2, and GALR3 mRNA expression was evaluated using quantitative real-time PCR, and pituitary galanin concentration was determined using a specific radioimmunoassay. The results revealed that estrogen predominantly induced a 5-fold increase in GALR3 gene transcription. To a lesser extent, 17β-estradiol also increased GALR1 mRNA expression, but had no effect on GALR2 mRNA levels. The estrogen-induced increase in GALR3 gene expression occurred exclusively through ESR1 activation. The increase in GALR1 gene expression occurred through activation of both estrogen receptor subtypes, but the ESR2 subtype was predominantly involved. Furthermore, the results revealed that progesterone regulates the activity of the pituitary galaninergic system by facilitating estradiol-induced galanin synthesis in the female rat anterior pituitary gland.

Background: The restoration of walking ability in the spinal cord injury (SCI) population is an increasingly important goal in physical therapy. Locomotor training (LT) is often implemented with the aim to restore ambulation. At this point, there are no guidelines for LT in the pediatric SCI population. Objectives: The aim of this review is to further narrow the effects of LT to the pediatric SCI population and develop recommendations for pediatric LT. Methods: A thorough search was performed using the following databases: Scopus, CINAHL, PubMed, and Ovid. Studies were selected based on the following inclusion criteria: pediatric SCI population, articles published within last 10 years, human subjects, and LT. Studies looking at other neurological disorders and subjects who were not previously ambulatory were excluded. Five students and one Faculty Research Advisor from the university's Doctor of Physical Therapy Program evaluated the inclusion criteria, conducted a risk of bias assessment using the Downs and Black checklist, and extracted the results. Results: Six studies were selected for this review. They showed gains in distance, gait speed, walking independence, and participation. There were variations in results when comparing gains in injury level based on the International Standards for Neurological Classification of Spinal Cord Injury (ISNCSCI). Conclusions: Currently there is insufficient evidence to determine the best clinical practice guidelines for rehabilitation using LT within the pediatric SCI population.

Introduction: A tear of the anterior cruciate ligament (ACL) represents a significant injury for an athlete that requires substantial time away from sport, and significant rehabilitation after reconstruction. The physical therapist is responsible to determine when a patient is capable of tolerating the physical demands of daily activities and to attempt to prevent re-injury. Physical or functional performance tests (FPTs) are one mechanism used to evaluate the athlete's physical skills and capabilities prior to returning to sports participation. The purpose of this systematic review is to critically examine the clinical utility of functional performance tests used with patients less than or equal to one year post ACL reconstruction., Methods: A systematic review of the relevant literature was performed using PRISMA guidelines. A total of twelve studies were included for analysis., Results: Two independent blinded reviewers then analyzed and rated the final included articles (n=12) utilizing the Newcastle-Ottawa Scale (NOS). Percent overall agreement between raters for the NOS was 88% with a fixed-marginal kappa (κ) of 0.80. Of the 12 included articles, the FPTs were utilized as an outcome measure within the study design (41.7%) or studied as a measure of function (58.3%). Among those studies that used FPTs as a "measure of function" 71.4% studied a battery of FPTs, while 28.6% studied a single test. None of the studies utilized FPTs as a measure to determine readiness to return to sport., Discussion: FPTs are being utilized with patients, less than or equal to one year post ACL reconstruction, either as an assessment of functional performance or as an outcome measure. No studies identified a FPT or test battery that has construct or predictive validity for "return to sport" in athletic population one-year post-ACL reconstruction. The identification of the critical elements within the return to sport construct may allow lower extremity performance tests to be developed or test batteries assembled to incorporate the appropriate tests to examine all of these elements deemed critical. Additionally the current FPTs should undergo content and predictive validation to assist the sports physical therapist in determining the readiness of the athlete for return to sport.

Background: Massachusetts has implemented reforms aimed at providing universal health care coverage and covers abortion through subsidized state insurance programs. Three Massachusetts abortion funds evaluated their referral processes for low-income women from April to October 2010 to learn about women's experiences applying for subsidized insurance and to identify barriers to obtaining insurance or its use for abortion services., Methods: Follow-up interviews were conducted with 39 low-income women thought eligible for subsidized insurance at least 1 month after their initial contact with the funds., Results: Health insurance literacy was low, and participants reported confusion distinguishing between levels of subsidized insurance. The process of applying for subsidized insurance delayed a substantial proportion of procedures. More than two thirds of the women who applied for state coverage had become insured or expected to become insured shortly, but only one third of respondents who applied were able to secure insurance in time for their abortion care. Two women were unable to obtain abortions as a result of delays. Delays also limited low-income women's ability to obtain medication abortion., Conclusion: This analysis suggests that the process for enrolling in subsidized insurance does not currently meet the goal of providing women with coverage for abortion care (and other health needs) in a timely way. Systemic improvements are needed to ensure that enrollments are processed quickly and disruptions in coverage are minimized. Information resources should be developed to help women and their families understand health insurance and coverage of services., (Copyright © 2011 Jacobs Institute of Women's Health. Published by Elsevier Inc. All rights reserved.)

B7-DC is a recently discovered member of the B7 family that binds to PD-1 and is selectively expressed by dendritic cells (DCs). It has been shown to either costimulate or inhibit T cell responses. To assess the role of B7-DC in DC-T cell interactions, DCs from B7-DC knockout (KO) mice were generated and compared with DCs from wild-type (WT) and B7-1/B7-2 double KO mice. B7-1/B7-2-deficient DCs, while strongly diminished in their ability to stimulate naive CD4+ T cells, nonetheless retain partial activity. DCs from B7-DC KO mice are diminished in their ability to activate CD4+ T cells, demonstrating that DC-expressed B7-DC serves a predominantly stimulatory rather than inhibitory function in the initiation of T cell responses. B7-DC costimulates expression of CD40L with faster kinetics than B7-1 and displays potent synergy with B7-1 and B7-2 for T cell proliferation and cytokine production, indicating that these B7 family members work in concert to stimulate T cells. Finally, costimulation with B7-DC alone or in conjunction with B7-1 is PD-1 independent, indicating that B7-DC costimulates T cells via a second receptor.

A major focus of cancer immunotherapy is to develop strategies to induce T-cell responses through presentation of tumor antigens by dendritic cells (DCs). Current vaccines are limited in their ability to efficiently transfer antigens to DCs in vivo. Ex vivo-generated DCs can be efficiently loaded with antigen but after reinjection, few DCs traffic to secondary lymphoid organs, the critical sites for antigen presentation. To enhance efficiency and durability of antigen presentation by DCs, we transduced hematopoietic stem-progenitor cells (HSCs) with a model tumor antigen and then transplanted the gene-modified cells into irradiated recipient mice, which resulted in efficient expression of the transgene in a large proportion of donor derived DCs in lymphoid organs. The combination of bone marrow transplantation (BMT) using transduced HSCs, systemic agents that generate and activate DCs, and mature T-cell infusion resulted in substantial expansion and activation of antigen-specific T cells. This tripartite strategy provided potent antigen-specific immunotherapy for an aggressive established tumor.

There is accumulating evidence that CD4(+) T cell responses are important in antitumor immunity. Accordingly, we generated CD4(+) T cells against the murine CT26 colon cancer. Three of three independent CT26-specific CD4(+) hybridomas were found to recognize the high m.w. precursor of the env gene product gp90. The CD4(+) response was completely tumor specific in that the same glycoprotein expressed by other tumors was not recognized by the CT26-specific hybridomas. The recognition of gp90 by the hybridomas was strictly dependent on the conformation of gp90. Different procedures that disrupted the conformation of the glycoprotein, such as disulfide bond reduction and thermal denaturation, completely abrogated recognition of gp90 by all three hybridomas. In CT26 cells, but not in other tumor cells tested, a large proportion of gp90 was retained in the endoplasmic reticulum, mostly bound to the endoplasmic reticulum chaperone, calreticulin. Although calreticulin was not essential for the stimulation of the gp90-specific hybridomas, most of the antigenic form of gp90 was bound to it. The antigenicity of gp90 correlated well with calreticulin binding, reflecting the fact that specificity of binding of calreticulin to its substrate required posttranslational modifications that were also necessary for the generation of this tumor-specific CD4(+) epitope.