Patient actions and reactions after receiving negative results from expanded carrier screening.

With the expansion of carrier screening to general preconception and prenatal patient populations, most patients will receive negative results, which we define as indicating <25% risk of having a child with a genetic condition. Because there is limited experience with expanded carrier screening, it is important to understand how receiving negative results affects patients, especially as providers, payers, and policymakers consider whether to offer it. In this mixed-methods study, we asked preconception patients enrolled in the NextGen study about their expectations and experiences receiving negative expanded carrier screening results. Participants completed surveys at study enrollment (n = 110 women, 51 male partners), after receiving carrier results (n = 100 women, 38 male partners), after receiving secondary findings (n = 98 women, 36 male partners), and 6 months after receiving results (n = 95 women, 28 male partners). We also interviewed a subset of participants 12 to 24 months after receiving results (n = 24 women, 12 male partners). We found minimal negative emotional impact and privacy concerns, increased confidence in reproductive plans, and few changes to health behaviors, although some patients made health decisions based on misunderstandings of their results. These findings suggest that expanded carrier screening causes minimal psychosocial harms, but systems are needed to reduce the risk of misinterpreting results.

Sun-induced fluorescence - a new probe of photosynthesis: First maps from the imaging spectrometer HyPlant.

Variations in photosynthesis still cause substantial uncertainties in predicting photosynthetic CO2 uptake rates and monitoring plant stress. Changes in actual photosynthesis that are not related to greenness of vegetation are difficult to measure by reflectance based optical remote sensing techniques. Several activities are underway to evaluate the sun-induced fluorescence signal on the ground and on a coarse spatial scale using space-borne imaging spectrometers. Intermediate-scale observations using airborne-based imaging spectroscopy, which are critical to bridge the existing gap between small-scale field studies and global observations, are still insufficient. Here we present the first validated maps of sun-induced fluorescence in that critical, intermediate spatial resolution, employing the novel airborne imaging spectrometer HyPlant. HyPlant has an unprecedented spectral resolution, which allows for the first time quantifying sun-induced fluorescence fluxes in physical units according to the Fraunhofer Line Depth Principle that exploits solar and atmospheric absorption bands. Maps of sun-induced fluorescence show a large spatial variability between different vegetation types, which complement classical remote sensing approaches. Different crop types largely differ in emitting fluorescence that additionally changes within the seasonal cycle and thus may be related to the seasonal activation and deactivation of the photosynthetic machinery. We argue that sun-induced fluorescence emission is related to two processes: (i) the total absorbed radiation by photosynthetically active chlorophyll; and (ii) the functional status of actual photosynthesis and vegetation stress.

Pain and fatigue as mediators of the relationship between mobility aid usage and depressive symptomatology in ambulatory individuals with SCI.

STUDY DESIGN: Cross-sectional cohort study. OBJECTIVES: To investigate a mediational model where pain (intensity and interference) and fatigue mediate the relationship between the use of mobility aids and moderate-to-severe depressive symptomatology among ambulatory participants with spinal cord injury (SCI). SETTING: A medical university in the southeastern United States. METHODS: Ambulatory adults (N=652) with chronic SCI responded to a mail-in survey. The Patient Health Questionnaire-9 was used to assess moderate-to-severe depressive symptomatology. The Brief Pain Inventory was used to assess pain intensity and interference, and the Modified Fatigue Impact Scale-5-item version was used to assess fatigue. Participants self-reported use of mobility aids. RESULTS: On examining mobility aids used for ambulation, 65% were found to have used at least one aid. Severe pain intensity was reported by 11%, and 14% reported severe pain interference. Disabling fatigue was reported by 10% of the participants. Twenty-one percent (n=138) reported moderate-to-severe levels of depressive symptoms. On examining the relationships between mobility aids and depressive symptomatology, using people as a mobility aid was associated with increased odds of depressive symptomatology (2.6) and always using a wheelchair was associated with lower odds (0.3). However, these relationships were no longer significant after controlling for the mediating variables pain intensity, pain interference and fatigue. CONCLUSIONS: Pain and fatigue mediate the relationship between usage of certain mobility aids and depressive symptomatology. The use of people to assist in ambulation is associated with greater odds of moderate-to-severe depressive symptomatology, while always using a wheelchair is associated with lower odds.

Cutaneous effects of BRAF inhibitor therapy: a case series.

BACKGROUND: The cutaneous effects of rapidly accelerated fibrosarcoma kinase B (BRAF) inhibitors are not well understood. Squamous cell carcinoma (SCC), keratoacanthoma, and photosensitivity have been described in patients taking BRAF inhibitors. PATIENTS AND METHODS: To characterize the timing and frequency of skin lesions in patients receiving BRAF inhibitor therapy, we utilized a retrospective case review of 53 patients undergoing treatment with BRAF inhibitors for 4-92 weeks of therapy. Patients were evaluated at baseline, and then followed at 4- to 12-week intervals. Charts were retrospectively reviewed, and the morphology and timing of cutaneous events were recorded. RESULTS: Thirty-three of the 53 charts met exclusion/inclusion criteria, 15 were treated with vemurafenib, and 18 were treated with GSK 2118436/GSK 1120212. Of 33 patients treated with BRAF inhibitor, 13 developed photosensitivity (39.4%), 10 developed actinic keratoses (30.3%), 10 developed warts (30.3%), and 6 developed SCC (18.2%). CONCLUSIONS: Multiple cutaneous findings were observed in the 33 patients taking BRAF inhibitors. The previously described association with SCC and photosensitivity was observed in these patients as well. Over half of the observed SCCs were invasive in nature. Photosensitivity continues to be frequent with BRAF inhibitors. Patients taking BRAF inhibitors should have regular full body skin exams. Further studies are necessary to better elucidate the rates of these adverse cutaneous effects.

Residency and space use estimation methods based on passive acoustic telemetry data.

Acoustic telemetry has helped overcome many of the challenges faced when studying the movement ecology of aquatic species, allowing to obtain unprecedented amounts of data. This has made it into one of the most widely used methods nowadays. Many ways to analyse acoustic telemetry data have been made available and deciding on how to analyse the data requires considering the type of research objectives, relevant properties of the data (e.g., resolution, study design, equipment), habits of the study species, researcher experience, among others. To ease this decision process, here we showcase (1) some of the methods used to estimate pseudo-positions and positions from raw acoustic telemetry data, (2) methods to estimate residency and (3) methods to estimate two-dimensional home and occurrence range using geometric or hull-based methods and density-distribution methods, a network-based approach, and three-dimensional methods. We provide examples of some of these were tested using a sample of real data. With this we intend to provide the necessary background for the selection of the method(s) that better fit specific research objectives when using acoustic telemetry.

Dose rate dependence for different dosimeters and detectors: TLD, OSL, EBT films, and diamond detectors.

PURPOSE: The use of laser accelerators in radiation therapy can perhaps increase the low number of proton and ion therapy facilities in some years due to the low investment costs and small size. The laser-based acceleration technology leads to a very high peak dose rate of about 10(11) Gy∕s. A first dosimetric task is the evaluation of dose rate dependence of clinical dosimeters and other detectors. METHODS: The measurements were done at ELBE, a superconductive linear electron accelerator which generates electron pulses with 5 ps length at 20 MeV. The different dose rates are reached by adjusting the number of electrons in one beam pulse. Three clinical dosimeters (TLD, OSL, and EBT radiochromic films) were irradiated with four different dose rates and nearly the same dose. A faraday cup, an integrating current transformer, and an ionization chamber were used to control the particle flux on the dosimeters. Furthermore two diamond detectors were tested. RESULTS: The dosimeters are dose rate independent up to 4●10(9) Gy∕s within 2% (OSL and TLD) and up to 15●10(9) Gy∕s within 5% (EBT films). The diamond detectors show strong dose rate dependence. CONCLUSIONS: TLD, OSL dosimeters, and EBT films are suitable for pulsed beams with a very high pulse dose rate like laser accelerated particle beams.

Calorimeter with Bayesian unfolding of spectra of high-flux broadband x rays.

We report the development of a multipurpose differential x-ray calorimeter with a broad energy bandwidth. The absorber architecture is combined with a Bayesian unfolding algorithm to unfold high energy x-ray spectra generated in high-intensity laser-matter interactions. Particularly, we show how to extract absolute energy spectra and how our unfolding algorithm can reconstruct features not included in the initial guess. The performance of the calorimeter is evaluated via Monte Carlo generated data. The method accuracy to reconstruct electron temperatures from bremsstrahlung is shown to be 5% for electron temperatures from 1 to 50 MeV. We study bremsstrahlung generated in solid target interaction showing an electron temperature of 0.56 ± 0.04 MeV for a 700 µm Ti titanium target and 0.53 ± 0.03 MeV for a 50 µm target. We investigate bremsstrahlung from a target irradiated by laser-wakefield accelerated electrons showing an endpoint energy of 551 ± 5 MeV, inverse Compton generated x rays with a peak energy of 1.1 MeV, and calibrated radioactive sources. The total energy range covered by all these sources ranges from 10 keV to 551 MeV.

Tetraspanins CD9 and CD81 are molecular partners of trimeric FcɛRI on human antigen-presenting cells.

BACKGROUND: Most functions of tetraspanins are not related to cell-surface receptor ligand binding, but are mediated by direct interactions with their partner proteins. Functions of trimeric FcɛRI, expressed by antigen-presenting cells (APCs), range from amplification of allergic inflammatory reactions to their active suppression. Cell-type-specific protein-protein interactions might play a role in the regulation of these bidirectional tasks. Therefore, we intended to study the interactions of trimeric FcɛRI with tetraspanins. METHODS: The expression levels of tetraspanins CD9, CD37, CD53, CD63, CD81, CD82, and CD151 on skin dendritic cells of atopic dermatitis (AD) patients or healthy individuals were detected by flow cytometry. Tetraspanin expression on FcɛRI(pos) and FcɛRI(neg) monocyte subpopulations was evaluated. Flow cytometry, confocal microscopy, immunoprecipitation, and immunoblotting experiments were performed to observe the relationship between tetraspanins CD9 and CD81 and FcɛRI. Furthermore, plate stimulation experiments were performed, and cytokines in the supernatants were detected. RESULTS: We found that human FcɛRI(pos) APCs expressed high amounts of tetraspanins and that the tetraspanins CD9 and CD81 were associated with FcɛRI. Concomitant activation of FcɛRI and CD9 on human monocytes increased FcɛRI-mediated cytokine release. CONCLUSION: Taken together, we show for the first time that CD9 and CD81 act as molecular partners of trimeric FcɛRI on human APC, which might be of importance in allergic diseases such as AD.

Horizontal and vertical angle kappa.

BACKGROUND: The aim of this study is to report the geometric range of angle kappa formation in patients with and without strabismus. PATIENTS AND METHODS: This is a retrospective study of three patients with angle kappa in different planes. Routine eye examinations, including visual acuity, slit-lamp examination, and ophthalmoscopy, were performed. A thorough orthoptic examination revealed a notable difference between the prism and alternate-cover test and the Hirschberg measurements. RESULTS: The first patient exhibited a bilateral vertical angle kappa into opposite directions due to retinochoroidal scars. Two other patients presented with horizontal angle kappa deviations. In one patient a true accommodative esotropia was exaggerated by a right negative angle kappa. The other patient had a pseudoexotropia due to bilateral positive angle kappa. Macular ectopia was noted in all cases. CONCLUSIONS: The patients herein reported demonstrate a marked variability of angle kappa occurrence in the horizontal and vertical plane. The angle kappa can exaggerate or conceal the size of the true heterotropia.

Proton beam quality enhancement by spectral phase control of a PW-class laser system.

We report on experimental investigations of proton acceleration from solid foils irradiated with PW-class laser-pulses, where highest proton cut-off energies were achieved for temporal pulse parameters that varied significantly from those of an ideally Fourier transform limited (FTL) pulse. Controlled spectral phase modulation of the driver laser by means of an acousto-optic programmable dispersive filter enabled us to manipulate the temporal shape of the last picoseconds around the main pulse and to study the effect on proton acceleration from thin foil targets. The results show that applying positive third order dispersion values to short pulses is favourable for proton acceleration and can lead to maximum energies of 70 MeV in target normal direction at 18 J laser energy for thin plastic foils, significantly enhancing the maximum energy compared to ideally compressed FTL pulses. The paper further proves the robustness and applicability of this enhancement effect for the use of different target materials and thicknesses as well as laser energy and temporal intensity contrast settings. We demonstrate that application relevant proton beam quality was reliably achieved over many months of operation with appropriate control of spectral phase and temporal contrast conditions using a state-of-the-art high-repetition rate PW laser system.

Broad Feshbach resonance in the 6Li-40K mixture.

We study the widths of interspecies Feshbach resonances in a mixture of the fermionic quantum gases 6Li and 40K. We develop a model to calculate the width and position of all available Feshbach resonances for a system. Using the model, we select the optimal resonance to study the {6}Li/{40}K mixture. Experimentally, we obtain the asymmetric Fano line shape of the interspecies elastic cross section by measuring the distillation rate of 6Li atoms from a potassium-rich 6Li/{40}K mixture as a function of magnetic field. This provides us with the first experimental determination of the width of a resonance in this mixture, DeltaB=1.5(5) G. Our results offer good perspectives for the observation of universal crossover physics using this mass-imbalanced fermionic mixture.

Hot electrons transverse refluxing in ultraintense laser-solid interactions.

We have analyzed the coupling of ultraintense lasers (at ∼2×10{19} W/cm{2}) with solid foils of limited transverse extent (∼10 s of µm) by monitoring the electrons and ions emitted from the target. We observe that reducing the target surface area allows electrons at the target surface to be reflected from the target edges during or shortly after the laser pulse. This transverse refluxing can maintain a hotter, denser and more homogeneous electron sheath around the target for a longer time. Consequently, when transverse refluxing takes places within the acceleration time of associated ions, we observe increased maximum proton energies (up to threefold), increased laser-to-ion conversion efficiency (up to a factor 30), and reduced divergence which bodes well for a number of applications.

Perceived parental rearing in subjects with obsessive-compulsive disorder and their siblings.

OBJECTIVE: Perceived parenting in patients suffering from obsessive-compulsive disorder (OCD) is examined. We attempted to overcome some methodological limitations of prior studies by taking age of onset, parental OCD and comorbid depression into consideration. In addition, we included data from unaffected siblings to corroborate information on parental rearing. METHOD: One hundred and twenty-two cases with OCD and 41 of their siblings as well as 59 healthy controls and 45 of their siblings completed the German short-version of the EMBU (FEE). RESULTS: Obsessive-compulsive disorder cases reported less parental warmth and more parental rejection and control. Further analyses indicated that parenting is also associated with OCD in cases with late onset and cases without parents affected by OCD. OCD cases with comorbid depression described their parents particularly negatively. Data from siblings indicated good validity of perceived parenting in OCD. CONCLUSION: This study provides further evidence for dysfunctional child rearing being relevant to the development of OCD and depression.

Lung tumor development and spontaneous regression in lambs coinfected with Jaagsiekte sheep retrovirus and ovine lentivirus.

Ovine pulmonary adenocarcinoma (OPA) is a naturally occurring and experimentally inducible lung cancer of sheep caused by Jaagsiekte sheep retrovirus (JSRV). The first aim of this study was to monitor the development of OPA with minimally invasive, real-time observations of animals experimentally infected with JSRV as well as ovine lentivirus (maedi-visna virus). Worldwide, simultaneous infection of sheep with these 2 retroviruses is a common occurrence, naturally and experimentally; consequently, the lung tumor homogenates used as inocula contained both viruses. Following inoculation, computed tomography was used to detect tumor nodules early, before the onset of clinical signs, and to monitor tumor advancement. However, not only was OPA disease progression observed, but the apparent spontaneous regression of OPA was witnessed. In fact, regression was more common than progression following JSRV inoculation of neonatal lambs. Immune responses were detected, particularly involving CD3(+) T cells and the production of antibodies against JSRV that may mediate the spontaneous regression of JSRV-induced OPA. The second aim of this study was to determine whether OPA tumors harbor genetic alterations similar to those found in human lung adenocarcinoma. No mutations were found in the tyrosine kinase domain of the epidermal growth factor receptor, KRAS codons 12 and 13, or the DNA-binding domain of p53 in tumor DNA from naturally occurring and experimentally-induced OPA cases. Overall, the genetic profile combined with the disease development data provides further important characterization of OPA and describes, for the first time, spontaneous regression of OPA tumors in experimentally infected sheep.

Immunoglobulin A: localization in rectal mucosal epithelial cells.

Immunofluorescence studies with monospecific antiserums to human serum immunoglobulins consistently revealed immunoglobulin A within the apical portion of the cytoplasm of rectal mucosal epithelial cells in normal subjects, as well as in patients with various bowel diseases. Immunoglobulins M, G, and D were not demonstrated within mucosal epithelial cells. The predominance of lymphoid cells containing immunoglobulin A in the lamina propria of intestinal tissues was confirmed.

Intraoperative intorsional traction test of the inferior oblique.

PurposeWe present a novel variation of the traction test of the inferior oblique (IO) muscle. We demonstrate the correlation between the traction test and clinically graded IO overaction and describe the utility of this test to confirm IO weakening.MethodsWe performed a retrospective chart review on all patients who underwent IO surgery and intraoperative intorsion traction tests by a single surgeon over a 10-year period. We compared the traction test results, in 'clock hours' of freedom, before and after IO surgery. We correlated the torsion test at start of surgery with clinical observed IO overaction (scale 0 to +4) in 67 IO operations (56 myectomies, 6 anterior transpositions, 4 myotomies, and 1 recession) and compared to a control group of 23 eyes with minimal or no IO overaction.ResultsThe mean intorsion freedom in the eyes undergoing IO surgery was less than in control eyes (1.63 vs 1.89 clock hour; P<0.00005). There was a significant inverse relationship between grading of clinical IO action and the intorsion test result (Pearson rank coefficient, (r=-0.45; P<0.00001)). Myectomy produced the greatest change in torsion freedom (mean 1.32 clock hour), with all myectomies showing at least 1 clock hour extra freedom after the surgery.ConclusionsThe intorsion traction test confirmed that the IO stiffness correlated with pre-operative IO overaction grade. While it can be helpful in confirming that the entire IO muscle was weakened, it does not substitute for the careful inspection at the end of surgery to ensure there are no remaining IO fibers.

The high-affinity IgE receptor (FcepsilonRI) blocks apoptosis in normal human monocytes.

Monocytes have a limited life span, and their homeostasis is regulated by apoptosis in vivo. When cultured in the absence of appropriate exogenous stimuli, they undergo apoptosis, but under the influence of survival signals, these cells differentiate into macrophages or dendritic cells. Here we show that ligation of the high-affinity IgE receptor (FcepsilonRI) on human monocytes from nonatopic individuals markedly reduces apoptosis induced by serum deprivation or by CD95/Fas ligation. Aggregation of FcepsilonRI reduces its own expression but fails to modulate CD95/Fas expression. In contrast, FcepsilonRI ligation enhances the expression of the antiapoptotic molecules Bcl-2 and Bcl-xL, but not Mcl-1, in monocytes. Incubation of unstimulated cells with culture supernatants of FcepsilonRI-activated monocytes prolongs their life span, whereas CD95/Fas expression remains unaffected. The incidence of apoptosis is restored considerably when the supernatant is depleted of TNF-alpha, whereas elimination of IL-1beta, GM-CSF, or IL-12 has no effect. These results indicate that FcepsilonRI mediates signals preventing monocyte apoptosis directly by increasing the levels of Bcl-2 and Bcl-xL, and indirectly by means of TNF-alpha in an autocrine and paracrine fashion. This process may contribute to the establishment of chronic allergic disorders such as atopic dermatitis.

IgE receptors.

IgE receptors are implicated as important components of the immunological pathway in allergic and inflammatory diseases. Recent investigations have begun to unravel the structure, signal transduction and function of IgE receptors from different cell types in rodent and human systems. Studies of the mechanisms involved might provide opportunities for therapeutic intervention strategies in the treatment of allergic and hypersensitivity reactions.

Referrals for movement disorder surgery: under-representation of females and reasons for refusal.

OBJECTIVE: Referral of movement disorder patients for deep brain stimulation surgery was examined to determine whether referred patients were representative of gender proportions in our population, and reasons why patients do not proceed to surgery. METHODS: Demographic information on referrals to the surgical program was retrospectively reviewed from our database and from a detailed chart review. RESULTS: Although almost equal numbers of movement disorder patients are male and female, of the 91 patients referred for surgery, only 31% were female. Sixty-one percent of referred patients did not undergo surgery. Of these, the majority were denied for medical reasons, including cognitive decline (21%), psychiatric concerns (5%) and neurological reasons (42%). CONCLUSIONS: Almost one-third of patients referred for movement disorder surgery were denied for medical reasons. This underscores the importance of evaluation of all potential patients by a multidisiplinary team to fully assess suitablity for stereotactic surgery. Interestingly, women were under-represented in those referred. In order that all appropriate patients have the opportunity to consider surgery, education of both physicians and patients, and different strategies to approach females regarding surgery may allow more patients to benefit from this treatment.