The impact of Cognitive Processing Therapy on stigma among survivors of sexual violence in eastern Democratic Republic of Congo: results from a cluster randomized controlled trial.

BACKGROUND: Sexual violence is associated with a multitude of poor physical, emotional, and social outcomes. Despite reports of stigma by sexual violence survivors, limited evidence exists on effective strategies to reduce stigma, particularly in conflict-affected settings. We sought to assess the effect of group Cognitive Processing Therapy (CPT) on stigma and the extent to which stigma might moderate the effectiveness of CPT in treating mental health problems among survivors of sexual violence in the Democratic Republic of Congo. METHODS: Data were drawn from 405 adult female survivors of sexual violence reporting mental distress and poor functioning in North and South Kivu. Women were recruited through organizations providing psychosocial support and then cluster randomized to group CPT or individual support. Women were assessed at baseline, the end of treatment, and again six months later. Assessors were masked to women's treatment assignment. Linear mixed-effect regression models were used to estimate (1) the effect of CPT on feelings of perceived and internalized (felt) stigma, and (2) whether felt stigma and discrimination (enacted stigma) moderated the effects of CPT on combined depression and anxiety symptoms, posttraumatic stress, and functional impairment. RESULTS: Participants receiving CPT experienced moderate reductions in felt stigma relative to those in individual support (Cohen's D = 0.44, p = value = 0.02) following the end of treatment, though this difference was no longer significant six-months later (Cohen's D = 0.45, p = value = 0.12). Neither felt nor enacted stigma significantly moderated the effect of CPT on mental health symptoms or functional impairment. CONCLUSIONS: Group cognitive-behavioral based therapies may be an effective stigma reduction tool for survivors of sexual violence. Experiences and perceptions of stigma did not hinder therapeutic effects of group psychotherapy on survivors' mental health. TRIAL REGISTRATION: ClinicalTrials.gov NCT01385163.

Functional characterisation of different MLL fusion proteins by using inducible Sleeping Beauty vectors.

Our focus is the identification, characterisation and functional analysis of different MLL fusions. In general, MLL fusion proteins are encoded by large cDNA cassettes that are difficult to transduce into haematopoietic stem cells. This is due to the size limitations of the packaging process of those vector-encoded RNAs into retro- or lentiviral particles. Here, we present our efforts in establishing a universal vector system to analyse different MLL fusions. The universal cloning system was embedded into the backbone of the Sleeping Beauty transposable element. This transposon has no size limitation and displays no integration preference, thereby avoiding the integration into active genes or their promoter regions. We utilised this novel system to test different MLL fusion alleles (MLL-NEBL, NEBL-MLL, MLL-LASP1, LASP1-MLL, MLL-MAML2, MAML2-MLL, MLL-SMAP1 and SMAP1-MLL) in appropriate cell lines. Stable cell lines were analysed for their growth behaviour, focus formation and colony formation capacity and ectopic Hoxa gene transcription. Our results show that only 1/4 tested direct MLL fusions, but 3/4 tested reciprocal MLL fusions exhibit oncogenic functions. From these pilot experiments, we conclude that a systematic analysis of more MLL fusions will result in a more differentiated picture about the oncogenic capacity of distinct MLL fusions.

Dual roles for Spt5 in pre-mRNA processing and transcription elongation revealed by identification of Spt5-associated proteins.

During transcription elongation, eukaryotic RNA polymerase II (Pol II) must contend with the barrier presented by nucleosomes. The conserved Spt4-Spt5 complex has been proposed to regulate elongation through nucleosomes by Pol II. To help define the mechanism of Spt5 function, we have characterized proteins that coimmunopurify with Spt5. Among these are the general elongation factors TFIIF and TFIIS as well as Spt6 and FACT, factors thought to regulate elongation through nucleosomes. Spt5 also coimmunopurified with the mRNA capping enzyme and cap methyltransferase, and spt4 and spt5 mutations displayed genetic interactions with mutations in capping enzyme genes. Additionally, we found that spt4 and spt5 mutations lead to accumulation of unspliced pre-mRNA. Spt5 also copurified with several previously unstudied proteins; we demonstrate that one of these is encoded by a new member of the SPT gene family. Finally, by immunoprecipitating these factors we found evidence that Spt5 participates in at least three Pol II complexes. These observations provide new evidence of roles for Spt4-Spt5 in pre-mRNA processing and transcription elongation.

fMRI response during visual motion stimulation in patients with late whiplash syndrome.

After whiplash trauma, up to one fourth of patients develop chronic symptoms including head and neck pain and cognitive disturbances. Resting perfusion single-photon-emission computed tomography (SPECT) found decreased temporoparietooccipital tracer uptake among these long-term symptomatic patients with late whiplash syndrome. As MT/MST (V5/V5a) are located in that area, this study addressed the question whether these patients show impairments in visual motion perception. We examined five symptomatic patients with late whiplash syndrome, five asymptomatic patients after whiplash trauma, and a control group of seven volunteers without the history of trauma. Tests for visual motion perception and functional magnetic resonance imaging (fMRI) measurements during visual motion stimulation were performed. Symptomatic patients showed a significant reduction in their ability to perceive coherent visual motion compared with controls, whereas the asymptomatic patients did not show this effect. fMRI activation was similar during random dot motion in all three groups, but was significantly decreased during coherent dot motion in the symptomatic patients compared with the other two groups. Reduced psychophysical motion performance and reduced fMRI responses in symptomatic patients with late whiplash syndrome both point to a functional impairment in cortical areas sensitive to coherent motion. Larger studies are needed to confirm these clinical and functional imaging results to provide a possible additional diagnostic criterion for the evaluation of patients with late whiplash syndrome.

Oligonucleotide-directed assembly of materials: defined oligomers.

A nano-architectural system that has high variability while maintaining component specificity is described. Tetraphenylcyclobutadiene(cyclopentadienyl)cobalt complexes and phenyleneethynylene trimers were synthesized and subsequently modified with oligonucleotides utilizing standard phosphoramidite chemistry. The resulting oligonucleotide modified organics (OMOs) were characterized by UV-vis spectroscopy, fluorescence spectroscopy, and phosphate analysis. Hybridization of these OMOs resulted in a series of self-assembled oligomeric hybrids of varying length and topology. These hybrids were characterized by melting temperature, polyacrylamide gel electrophoresis, and fluorescence spectroscopy. This model system demonstrates the power of DNA to self-assemble modules of interest-independent of the module itself.

[Dorsal V-ligament reconstruction in scapholunate instability]. / Die dorsale V-Bandplastik zur Therapie der posttraumatischen skapholunären Instabilität.

In dynamic and static scapholunate instability after trauma, the repair of the scapholunate ligament is important to avoid scapholunate advanced collapse of the wrist. Direct suture even of fresh-torn ligaments can be technically demanding and occasionally unreliable, thus reconstruction may require additional tissue beside the ligament. Eighteen patients suffering from dynamic (n = 10) and static (n = 8) scapholunate instability were treated by a dorsal ligament reconstruction six months after trauma. A clinical wrist score according to Cooney showed an average of 86 points (maximum 100) within a follow-up of nineteen months after surgery. X-ray films documented no significant loss of scapholunate reduction. Using local tissue only, this method is always possible, very reliable and easy to perform.

Correlation bias in U.S. census adjustment.

One form of error that can affect census adjustments is correlation bias, reflecting people who are doubly missing--from the census and from the adjusted counts as well. This article presents a method for estimating the total national number of doubly-missing people and their distribution by race and sex. Application to the 1990 U.S. census adjustment leads to an estimate of 3 million doubly-missing people. Correlation bias is likely to be a serious problem for census adjustment in 2000. The methods of this article are well suited for measuring its magnitude.

Evolutionary demographic models for mortality plateaus.

Plateaus in the age pattern of hazard functions at extreme ages have been discovered in large populations of medflies, Drosophila, nematodes, and people. Mueller and Rose [(1996) Proc. Natl. Acad. Sci. USA 93, 15249-15253] have proposed several age-structured demographic models to represent effects of mutation accumulation and antagonistic pleiotropy on randomly evolving schedules of demographic rates. They assert that "evolutionary theory [as embodied in their models] predicts late-life mortality plateaus." This paper defines a class of Markovian models that includes those of Mueller and Rose and obtains a characterization of the possible limiting states. For the basic model, the result implies that schedules with late-life mortality plateaus above a minimal threshold are not limiting states. The models fail, but not for reasons previously conjectured. Transient states, visited early by the process, do display mortality plateaus. Other models from this class may have a role to play in reconciling observed plateaus with evolutionary theory.

PET and SPECT in whiplash syndrome: a new approach to a forgotten brain?

Whiplash associated disorders are a medicolegally controversial condition becoming increasingly worrisome in the western world. This study was designed to evaluate perfusion and glucose metabolism in whiplash brain. Using Tc-99m-bicisate (ECD) single photon emission computed tomography (SPECT) and F-18-fluorodeoxyglucose (FDG) PET, six clinically and neuropsychologically controlled patients (patient group) with whiplash syndrome and 12 normal controls (control group) were investigated. Standardised elliptical regions of interest (ROIs) were determined in three adjacent transaxial slices in the frontal, parietal, temporal, and parieto-occipital cortex, cerebellum, brain stem, basal ganglia, and thalamus. For PET, the glucose metabolic index (GMI; =ROI uptake/global uptake at the level of the basal ganglia) and, for SPECT, the perfusion index (PI; =ROI/global) were calculated. In the patient group there was significant hypometabolism and hypoperfusion in the parieto-occipital regions (on the right (R) and left (L) side) compared with the control group: PET data: GMI parieto-occipital R: control 1.066 (0.081) (mean (SD)), patient 0.946 (0.065); P=0.0092, Mann Whitney. GMI parieto-occipital L: control 1.034 (0.051), patient 0.922 (0.073); p=0.0067. SPECT data: PI parieto-occipital R: control 1.262 (0.066), patient 1.102 (0.063); P=0.0039. PI parieto-occipital L: control 1.226 (0.095), patient 1.098 (0.075); P=0.0273. In some patients there was hypometabolism (>2 SD of control) in regions other than the parieto-occipital region. It is hypothesised that parieto-occipital hypometabolism may be caused by activation ofnociceptive afferent nerves from the upper cervical spine.

Kinship resources for the elderly.

As population ageing strains social insurance systems, cohorts whose own fertility was low will be reaching elderly status, leaving close biological kin in short supply. However, there is a countervailing trend, inasmuch as burgeoning divorce, remarriage and family blending have expanded the numbers and varieties of step-kin and other non-standard kinship ties. Methods of computer microsimulation in conjunction with richer sample surveys can help us to foresee the contours of kin numbers and kinship relations in the future. Prime areas include the likely frequency of kin-deprived elderly, the overlap with economic deprivation and the interaction between kin frequency and intensity of contact. Step-ties may be weaker but nonetheless critical in raising the probability of at least one compatible member with whom one can choose to maintain contact and rely on. Kinship networks extended through half- and step-links, by stretching across racial and economic lines, may promote social cohesion.

Muscle damping measured with a modified pendulum test in patients with fibromyalgia, lumbago, and cervical syndrome.

STUDY DESIGN: Muscle tension with tenderness may be localized or generalized as in fibromyalgia. Wartenberg's pendulum test might be appropriate for quantitating muscle damping, at least in generalized cases. OBJECTIVE: Damping values provide a quantitative measure of muscle tension and of the response to various treatments. SUMMARY OF THE BACKGROUND DATA: According to recent anatomic and experimental works, intrafusal muscle fibers are double-innervated by gamma motoneurons and sympathetic fibers. With electromyograph recording, the activity of extrafusal fibers and gamma motoneurons (reflexes) can be assessed and separated from the action of the sympathetic system. METHODS: An electrogoniometer registers the movements of the freely swinging leg. On the oscilloscope, the patient's nodular curve is compared with an ideal calculated dampened curve to find the damping value. Electromyograph surface electrodes from the knee extensors and flexors detect the activity of extrafusal fibers and the occurrence of reflexes. RESULTS: In longstanding severe fibromyalgia, damping values are almost always elevated, at least in one leg. Half or more of patients with chronic lumbago and cervical syndrome present with increased damping. The surface electromyograph remains silent (in contrast to spastic patients). CONCLUSION: The findings support the hypothesis that muscle tension in rheumatic patients results from overactivity of the sympathetic system (or part of it). Even in clinically localized pain syndromes, muscle damping is often increased in the legs. The test is valuable for quantitating muscle tension and the effectiveness of therapeutic methods.

Evaluating the Slavonian census of 1698. Part I: structure and meaning.

"Microsimulation, other demographic tools, and evidence of history and ethnography are used to evaluate an important 17th century household census [in Slavonia, which is modern Croatia]. Linguistic, ethnographic, and internal evidence allow adjustment of anomalies in census categories. Microsimulation based on historically and ethnographically plausible rates and household formation scenarios produces simulated households in accord with those of the adjusted census. Results permit estimation of the true population of the region, of the kinship and age composition of households under frontier conditions, and the probable future composition of households as the frontier stabilized and land shortage began to exert pressure for greater density and household complexity. Part I concentrates on historical, ethnographic, and linguistic evidence." (SUMMARY IN FRE)

The cohort feedback model with symmetric net maternity.

"In this paper we consider the simplest and most widely used demographic feedback model, the birth-response cohort feedback model. In the case of symmetric net maternity, we put the model into a form in which one of the rare global bifurcation theorems in the mathematical literature can be brought to bear. As a consequence, we prove that the model has solutions with period exactly twice the mean age of net maternity for at least a specified range of parameter values which include cycles of non-infinitesimal amplitude." (SUMMARY IN FRE)

Synchronization of hormonal time series: analytical approaches.

Comparison of the patterns of episodic secretion of two or more hormones measured simultaneously often suggests that peak levels tend to occur at around the same time. This visual impression can be misleading, however, as some peaks will occur simultaneously due to chance alone. Traditional cross-correlation methods are suitable for evaluating linkages among circadian and other smoothly varying rhythms, but are less well suited to correlating ultradian peaks. This paper proposes a method which entails identifying peaks of hormone secretion as discrete events in several different series, and counting the frequency of simultaneous and near-simultaneous peaks in temporal 'windows' of increasing width. The expected rates of random coincidences can be assessed by a variety of methods, including simulations and probability calculations. The method described utilizes simple techniques which make few assumptions about the character or stationarity of the series, comparing coincidence rates in the appropriately paired series with those in which a series in one subject is deliberately 'mismatched' with that of another subject. Using this approach, a significant excess of simultaneous peaks of luteinizing hormone (LH) and prolactin was found in normal subjects as compared with mismatched series (17% versus 6%; p less than 0.05). Hypogonadotrophic men treated with pulsatile gonadotrophin-releasing hormone (GnRH) have an even higher coincidence rate (26%). By contrast, the rate of coincidence between pulses of LH and cortisol is not significantly greater than that which would be expected due to chance.

Pre-procreative ages in population stability and cyclicity.

"Humans' protracted maturation before childbearing is an extreme example of a general characteristic of higher organisms: a positive lower bound on ages of procreation. The pre-procreative span, much discussed for its evolutionary and social ramifications, has consequences also for the mathematics of population renewal.... This paper proves the presence of a pre-procreative span sufficient, in and of itself, to guarantee the existence condition for bifurcation for all models in one important class. The class includes the best-studied examples of age-specific systems with and without homeostatic feedback in purely discrete and in purely continuous formulations."

U.S. births and limit cycle models.

Lee's (1974) formal demographic feedback models summarize the implications for births and age-structure of neo-Malthusian theories of baby booms such as those of Easterlin. For some parameter values, such models imply sustained cycles, so-called "limit cycles", in births. Frauenthal and Swick recently reestimated a continuous-age version of Lee's basic cohort model with U.S. series and, contrary to Lee's original findings, concluded that "limit cycles oscillations have been occurring in U.S. births." This article disputes their conclusion, ascribing it to an inconsistency in detrending procedures. Furthermore, it corrects Lee's original conclusion by showing that his alternative period labor-force feedback model, estimated from U.S. series, leads to cycles of implausibly long period. This article thus reopens the question of whether any feedback model could account for the observed cycles in U.S. births.

Methods for assessing the linkage between pulsatile hormone profiles.

Although the different anterior pituitary hormones are generally considered to be regulated independently, examination of their patterns in blood suggests that pulsatile secretion of several of these hormones may be synchronized. Traditional methods of cross-correlation analysis may not be adequate for quantifying this linkage. Since some simultaneity may arise by chance, expected rates of random coincidences must also be estimated to determine if apparent concordance rates significantly exceed those due to chance. A method of estimating linkage by counting simultaneous and near-simultaneous events within temporal 'windows' of varying width is proposed and tested against 11 series of luteinizing hormone (LH) and prolactin measurements from normal men. Rates of concordance in series drawn from different subjects rather than the same subject, or series scrambled in time, do not contain meaningful simultaneous events and so can be used to estimate the rate of random synchrony. By these standards, a clear excess of concordant prolactin and luteinizing hormone (LH) peaks was observed in normal men, suggesting significant physiological synchrony between these pulses of secretion. This method can be applied to a variety of hormonal systems.