Use of diffusion spectrum imaging in preliminary longitudinal evaluation of amyotrophic lateral sclerosis: Development of an imaging biomarker

Previous diffusion tensor imaging (DTI) studies have shown white matter pathology in amyotrophic lateral sclerosis (ALS), predominantly in the motor pathways. Further these studies have shown that DTI can be used longitudinally to track pathology over time, making white matter pathology a candidate as an outcome measure in future trials. DTI has demonstrated application in group studies, however its derived indices, for example fractional anisotropy, are susceptible to partial volume effects, making its role questionable in examining individual progression. We hypothesize that changes in the white matter are present in ALS beyond the motor tracts, and that the affected pathways and associated pattern of disease progression can be tracked longitudinally using automated diffusion connectometry analysis. Connectometry analysis is based on diffusion spectrum imaging and overcomes the limitations of a conventional tractography approach and DTI. The identified affected white matter tracts can then be assessed in a targeted fashion using High definition fiber tractography (a novel white matter MR imaging technique). Changes in quantitative and qualitative markers over time could then be correlated with clinical progression. We illustrate these principles toward developing an imaging biomarker for demonstrating individual progression, by presenting results for five ALS patients, including with longitudinal data in two. Preliminary analysis demonstrated a number of changes bilaterally and asymmetrically in motoric and extramotoric white matter pathways. Further the limbic system was also affected possibly explaining the cognitive symptoms in ALS. In the two longitudinal subjects, the white matter changes were less extensive at baseline, although there was evidence of disease progression in a frontal pattern with a relatively spared postcentral gyrus, consistent with the known pathology in ALS. © 2014 Abhinav, Yeh, El-Dokla, Ferrando, Chang, Lacomis, Friedlander and Fernandez-Miranda

Controllability and controller-observer design for a class of linear time-varying systems

“The final publication is available at Springer via http://dx.doi.org/10.1007/s10852-012-9212-6"In this paper a class of linear time-varying control systems is considered. The time variation consists of a scalar time-varying coefficient multiplying the state matrix of an otherwise time-invariant system. Under very weak assumptions of this coefficient, we show that the controllability can be assessed by an algebraic rank condition, Kalman canonical decomposition is possible, and we give a method for designing a linear state-feedback controller and Luenberger observer

Deciphering interplay between Salmonella invasion effectors

Bacterial pathogens have evolved a specialized type III secretion system (T3SS) to translocate virulence effector proteins directly into eukaryotic target cells. Salmonellae deploy effectors that trigger localized actin reorganization to force their own entry into non-phagocytic host cells. Six effectors (SipC, SipA, SopE/2, SopB, SptP) can individually manipulate actin dynamics at the plasma membrane, which acts as a ‘signaling hub’ during Salmonella invasion. The extent of crosstalk between these spatially coincident effectors remains unknown. Here we describe trans and cis binary entry effector interplay (BENEFIT) screens that systematically examine functional associations between effectors following their delivery into the host cell. The results reveal extensive ordered synergistic and antagonistic relationships and their relative potency, and illuminate an unexpectedly sophisticated signaling network evolved through longstanding pathogen–host interaction

Coherent spinor dynamics in a spin-1 Bose condensate

Collisions in a thermal gas are perceived as random or incoherent as a consequence of the large numbers of initial and final quantum states accessible to the system. In a quantum gas, e.g. a Bose-Einstein condensate or a degenerate Fermi gas, the phase space accessible to low energy collisions is so restricted that collisions be-come coherent and reversible. Here, we report the observation of coherent spin-changing collisions in a gas of spin-1 bosons. Starting with condensates occupying two spin states, a condensate in the third spin state is coherently and reversibly created by atomic collisions. The observed dynamics are analogous to Josephson oscillations in weakly connected superconductors and represent a type of matter-wave four-wave mixing. The spin-dependent scattering length is determined from these oscillations to be -1.45(18) Bohr. Finally, we demonstrate coherent control of the evolution of the system by applying differential phase shifts to the spin states using magnetic fields.Comment: 19 pages, 3 figure

Psychological processes mediating the association between developmental trauma and specific psychotic symptoms in adults: a systematic review and meta-analysis

Experiencing psychological trauma during childhood and/or adolescence is associated with an increased risk of psychosis in adulthood. However, we lack a clear knowledge of how developmental trauma induces vulnerability to psychotic symptoms. Understanding the psychological processes involved in this association is crucial to the development of preventive interventions and improved treatments. We sought to systematically review the literature and combine findings using meta‐analytic techniques to establish the potential roles of psychological processes in the associations between developmental trauma and specific psychotic experiences (i.e., hallucinations, delusions and paranoia). Twenty‐two studies met our inclusion criteria. We found mediating roles of dissociation, emotional dysregulation and post‐traumatic stress disorder (PTSD) symptoms (avoidance, numbing and hyperarousal) between developmental trauma and hallucinations. There was also evidence of a mediating role of negative schemata, i.e. mental constructs of meanings, between developmental trauma and delusions as well as paranoia. Many studies to date have been of poor quality, and the field is limited by mostly cross‐sectional research. Our findings suggest that there may be distinct psy­chological pathways from developmental trauma to psychotic phenomena in adulthood. Clinicians should carefully ask people with psychosis about their history of developmental trauma, and screen patients with such a history for dissociation, emotional dysregulation and PTSD symptoms. Well conducted research with prospective designs, including neurocognitive assessment, is required in order to fully understand the biopsychosocial mechanisms underlying the association between developmental trauma and psychosis

Evaluation of the influence of kyphosis and scoliosis on intervertebral disc extrusion in French bulldogs

Although thoracic vertebral malformations with kyphosis and scoliosis are often considered incidental findings on diagnostic imaging studies of screw-tailed brachycephalic breeds, they have been suggested to interfere with spinal biomechanics and intervertebral disc degeneration. It is however unknown if an abnormal spinal curvature also predisposes dogs to develop clinically relevant intervertebral disc herniations. The aim of this study was to evaluate if the occurrence of thoracic vertebral malformations, kyphosis or scoliosis would be associated with a higher prevalence of cervical or thoracolumbar intervertebral disc extrusion in French bulldogs

Constitutive cytoplasmic localization of p21Waf1/Cip1 affects the apoptotic process in monocytic leukaemia

In the present study, we analysed the expression and localization of p21Waf1/Cip1 in normal and malignant haematopoietic cells. We demonstrate that in normal monocytic cells, protein kinase C (PKC)-induced p21 gene activation, which is nuclear factor-κB (NF-κB) independent, results in predominantly cytoplasmic localized p21 protein. In acute monocytic leukaemia (M4, M5), monocytic blasts (N=12) show constitutive cytoplasmic p21 expression in 75% of the cases, while in myeloid leukaemic blasts (N=10), low nuclear and cytoplasmic localization of p21 could be detected, which is also PKC dependent. Constitutive p21 expression in monocytic leukaemia might have important antiapoptotic functions. This is supported by the finding that in U937 cells overexpressing p21, VP16-induced apoptosis is significantly reduced (20.0±0.9 vs 55.8±3.8%, P<0.01, N=5), reflected by a reduced phosphorylation of p38 and JNK. Similarly, AML blasts with high cytoplasmic p21 were less sensitive to VP16-induced apoptosis as compared to AML cases with low or undetectable p21 expression (42.25 vs 12.3%, P<0.01). Moreover, complex formation between p21 and ASK1 could be demonstrated in AML cells, by means of coimmunoprecipitation. In summary, these results indicate that p21 has an antiapoptotic role in monocytic leukaemia, and that p21 expression is regulated in a PKC-dependent and NF-κB independent manner.

Implementation and evaluation of a harm-reduction model for clinical care of substance using pregnant women

<p>Abstract</p> <p>Background</p> <p>Methamphetamine (MA) use during pregnancy is associated with many pregnancy complications, including preterm birth, small for gestational age, preeclampsia, and abruption. Hawaii has lead the nation in MA use for many years, yet prior to 2007, did not have a comprehensive plan to care for pregnant substance-using women. In 2006, the Hawaii State Legislature funded a pilot perinatal addiction clinic. The Perinatal Addiction Treatment Clinic of Hawaii was built on a harm-reduction model, encompassing perinatal care, transportation, child-care, social services, family planning, motivational incentives, and addiction medicine. We present the implementation model and results from our first one hundred three infants (103) seen over 3 years of operation of the program.</p> <p>Methods</p> <p>Referrals came from community health centers, hospitals, addiction treatment facilities, private physician offices, homeless outreach services and self-referral through word-of-mouth and bus ads. Data to describe sample characteristics and outcome was obtained prospectively and retrospectively from chart abstraction and delivery data. Drug use data was obtained from the women's self-report and random urine toxicology during the pregnancy, as well as urine toxicology at the time of birth on mothers, and urine and meconium toxicology on the infants. Post-partum depression was measured in mothers with the Edinburgh Post-Partum depression scale. Data from Path clinic patients were compared with a representative cohort of women delivering at Kapiolani Medical Center for Women and Children during the same time frame, who were enrolled in another study of pregnancy outcomes. Ethical approval for this study was obtained through the University of Hawaii Committee for Human Studies.</p> <p>Results</p> <p>Between April 2007 and August 2010, 213 women with a past or present history of addiction were seen, 132 were pregnant and 97 delivered during that time. 103 live-born infants were delivered. There were 3 first-trimester Spontaneous Abortions, two 28-week intrauterine fetal deaths, and two sets of twins and 4 repeat pregnancies. Over 50% of the women had lost custody of previous children due to substance use. The majority of women who delivered used methamphetamine (86%), either in the year before pregnancy or during pregnancy. Other drugs include marijuana (59.8%), cocaine (33%), opiates (9.6%), and alcohol (15.2%). Of the women served, 85% smoked cigarettes upon enrollment. Of the 97 women delivered during this period, all but 4 (96%) had negative urine toxicology at the time of delivery. Of the 103 infants, 13 (12.6%) were born preterm, equal to the state and national average, despite having many risk factors for prematurity, including poverty, poor diet, smoking and polysubstance use. Overwhelmingly, the women are parenting their children, > 90% retained custody at 8 weeks. Long-term follow-up showed that women who maintained custody chose long-acting contraceptive methods; while those who lost custody had a very high (> 50%) repeat pregnancy rate at 9 months post delivery.</p> <p>Conclusion</p> <p>Methamphetamine use during pregnancy doesn't exist is isolation. It is often combined with a multitude of other adverse circumstances, including poverty, interpersonal violence, psychiatric comorbidity, polysubstance use, nutritional deficiencies, inadequate health care and stressful life experiences. A comprehensive harm reduction model of perinatal care, which aims to ameliorate some of these difficulties for substance-using women without mandating abstinence, provides exceptional birth outcomes and can be implemented with limited resources.</p

Melting of a 2D Quantum Electron Solid in High Magnetic Field

The melting temperature ($T_m$) of a solid is generally determined by the pressure applied to it, or indirectly by its density ($n$) through the equation of state. This remains true even for helium solids\cite{wilk:67}, where quantum effects often lead to unusual properties\cite{ekim:04}. In this letter we present experimental evidence to show that for a two dimensional (2D) solid formed by electrons in a semiconductor sample under a strong perpendicular magnetic field\cite{shay:97} ($B$), the $T_m$ is not controlled by $n$, but effectively by the \textit{quantum correlation} between the electrons through the Landau level filling factor $\nu$=$nh/eB$. Such melting behavior, different from that of all other known solids (including a classical 2D electron solid at zero magnetic field\cite{grim:79}), attests to the quantum nature of the magnetic field induced electron solid. Moreover, we found the $T_m$ to increase with the strength of the sample-dependent disorder that pins the electron solid.Comment: Some typos corrected and 2 references added. Final version with minor editoriol revisions published in Nature Physic

Quantum Point Contacts and Coherent Electron Focusing

I. Introduction II. Electrons at the Fermi level III. Conductance quantization of a quantum point contact IV. Optical analogue of the conductance quantization V. Classical electron focusing VI. Electron focusing as a transmission problem VII. Coherent electron focusing (Experiment, Skipping orbits and magnetic edge states, Mode-interference and coherent electron focusing) VIII. Other mode-interference phenomenaComment: #3 of a series of 4 legacy reviews on QPC'