Variable but not random: temporal pattern coding in a songbird brain area necessary for song modification.

Practice of a complex motor gesture involves motor exploration to attain a better match to target, but little is known about the neural code for such exploration. We examine spiking in a premotor area of the songbird brain critical for song modification and quantify correlations between spiking and time in the motor sequence. While isolated spikes code for time in song during performance of song to a female bird, extended strings of spiking and silence, particularly bursts, code for time in song during undirected (solo) singing, or "practice." Bursts code for particular times in song with more information than individual spikes, and this spike-spike synergy is significantly higher during undirected singing. The observed pattern information cannot be accounted for by a Poisson model with a matched time-varying rate, indicating that the precise timing of spikes in both bursts in undirected singing and isolated spikes in directed singing code for song with a temporal code. Temporal coding during practice supports the hypothesis that lateral magnocellular nucleus of the anterior nidopallium neurons actively guide song modification at local instances in time.NEW & NOTEWORTHY This paper shows that bursts of spikes in the songbird brain during practice carry information about the output motor pattern. The brain's code for song changes with social context, in performance versus practice. Synergistic combinations of spiking and silence code for time in the bird's song. This is one of the first uses of information theory to quantify neural information about a motor output. This activity may guide changes to the song.

Can quantitative computed tomography detect bone morphological changes associated with catastrophic proximal sesamoid bone fracture in Thoroughbred racehorses?

BACKGROUND: Fracture of the proximal sesamoid bones continues to be the most common fatal musculoskeletal injury in US racehorses. Identifying factors that influence fracture risk could lead to screening techniques to reduce catastrophic injury rates and improve animal welfare. OBJECTIVES: To identify morphological differences between proximal sesamoid bones of the contralateral limb of fracture and control horses and assess the feasibility of computed tomography (CT) to detect traits associated with proximal sesamoid bone fracture. We hypothesised that horses with proximal sesamoid bone fracture would have greater bone density. STUDY DESIGN: Cross-sectional cadaver morphological study. METHODS: Proximal sesamoid bone morphology was measured using high-resolution micro-CT images from 16 Thoroughbred racehorses (eight fracture, eight control) euthanised on New York racetracks. Nominal logistic regression models and receiver operating characteristic curves were created to assess the ability of CT-derived morphological traits to accurately classify fracture horses vs. controls. RESULTS: Bone volume fraction was greater in the fracture group (90.39 ± 1.76%) as compared to controls (87.20 ± 2.79%, P<0.0001). Bone volume fraction, bone width, trabecular thickness and degree of anisotropy were significantly different between fracture and control horses. Receiver operating characteristic curves showed that a combined model that incorporates bone volume fraction and width can identify fracture from control horses with an area under the curve of 0.938, indicating high accuracy at classifying fracture horses from controls. MAIN LIMITATIONS: The number of horses per group is small, although the total number of sesamoids imaged is reasonable (n = 62). In vivo CT at the resolution performed in this study is currently unattainable; however, density and width could be measured with quantitative CT. CONCLUSIONS: Differences in proximal sesamoid bone morphology were identified between fracture and control horses. As improved technology becomes accessible, quantitative CT could potentially be used as a clinical imaging technique to estimate proximal sesamoid bone fracture risk in Thoroughbred racehorses.

Genome-wide studies in multiple myeloma identify XPO1/CRM1 as a critical target validated using the selective nuclear export inhibitor KPT-276.

RNA interference screening identified XPO1 (exportin 1) among the 55 most vulnerable targets in multiple myeloma (MM). XPO1 encodes CRM1, a nuclear export protein. XPO1 expression increases with MM disease progression. Patients with MM have a higher expression of XPO1 compared with normal plasma cells (P<0.04) and to patients with monoclonal gammopathy of undetermined significance/smoldering MM (P<0.0001). The highest XPO1 level was found in human MM cell lines (HMCLs). A selective inhibitor of nuclear export compound KPT-276 specifically and irreversibly inhibits the nuclear export function of XPO1. The viability of 12 HMCLs treated with KTP-276 was significantly reduced. KPT-276 also actively induced apoptosis in primary MM patient samples. In gene expression analyses, two genes of probable relevance were dysregulated by KPT-276: cell division cycle 25 homolog A (CDC25A) and bromodomain-containing protein 4 (BRD4), both of which are associated with c-MYC pathway. Western blotting and reverse transcription-PCR confirm that c-MYC, CDC25A and BRD4 are all downregulated after treatment with KPT-276. KPT-276 reduced monoclonal spikes in the Vk*MYC transgenic MM mouse model, and inhibited tumor growth in a xenograft MM mouse model. A phase I clinical trial of an analog of KPT-276 is ongoing in hematological malignancies including MM.

Treatment intensification does not reduce residual HIV-1 viremia in patients on highly active antiretroviral therapy.

In HIV-1-infected individuals on currently recommended antiretroviral therapy (ART), viremia is reduced to <50 copies of HIV-1 RNA per milliliter, but low-level residual viremia appears to persist over the lifetimes of most infected individuals. There is controversy over whether the residual viremia results from ongoing cycles of viral replication. To address this question, we conducted 2 prospective studies to assess the effect of ART intensification with an additional potent drug on residual viremia in 9 HIV-1-infected individuals on successful ART. By using an HIV-1 RNA assay with single-copy sensitivity, we found that levels of viremia were not reduced by ART intensification with any of 3 different antiretroviral drugs (efavirenz, lopinavir/ritonavir, or atazanavir/ritonavir). The lack of response was not associated with the presence of drug-resistant virus or suboptimal drug concentrations. Our results suggest that residual viremia is not the product of ongoing, complete cycles of viral replication, but rather of virus output from stable reservoirs of infection.

Of holes and wholes: the perception of surrounded regions.

Fully enclosed regions in a two-dimensional image can often be perceived either as an object in front of a surface or as a hole through a surface. Several experiments were conducted to determine what factors affect perception of holes versus objects. Three types of factors were tested and found to influence this outcome. First, depth factors directly indicate that the enclosed region lies behind its surrounding surface. Second, grouping factors relate the enclosed region to an outer region that is generally perceived as a continuation of the surface seen through the hole. Finally, figural factors indicate whether the enclosed region is to be perceived as figure or ground. Relations among these factors and their implications for perceptual organization are discussed.

Survivors of childhood abuse: their reported experiences with professional help.

This article analyzes the self-reports of 384 adults who responded to a survey of people abused physically, sexually, or emotionally by family members in childhood. Most of the respondents sought help as adults from social workers and other mental health professionals for the long-term effects of their abusive experiences. This article analyses the reports of their help-seeking experiences against a backdrop of the reports of clinicians and researchers on working with survivors, as reported in the literature. Although survivors of childhood abuse often are described as having difficulty relating to professionals, these respondents persisted in seeking help and tended to report at least one experience with professional services that was very helpful. Their self-esteem and family functioning in adulthood was associated with having had a very helpful professional or service provider. The findings describe the responses most valued by survivors, as well as their views of the limitations of available services.

DNA ligase IV mutations identified in patients exhibiting developmental delay and immunodeficiency.

DNA ligase IV functions in DNA nonhomologous end-joining and V(D)J recombination. Four patients with features including immunodeficiency and developmental and growth delay were found to have mutations in the gene encoding DNA ligase IV (LIG4). Their clinical phenotype closely resembles the DNA damage response disorder, Nijmegen breakage syndrome (NBS). Some of the mutations identified in the patients directly disrupt the ligase domain while others impair the interaction between DNA ligase IV and Xrcc-4. Cell lines from the patients show pronounced radiosensitivity. Unlike NBS cell lines, they show normal cell cycle checkpoint responses but impaired DNA double-strand break rejoining. An unexpected V(D)J recombination phenotype is observed involving a small decrease in rejoining frequency coupled with elevated imprecision at signal junctions.

Late influences on perceptual grouping: illusory figures.

Two experiments demonstrate that grouping can be strongly influenced by the presence of figures defined by illusory contours. Rectangular arrays were constructed in which a central column of figures could group either with those on one side, on the basis of perception of figures defined by illusory contours, or with those on the other side, on the basis of physically present inducing elements. In all displays, subjects grouped according to the illusory figures significantly more often than for control displays that contained the same inducing elements, but rearranged so that illusory contours were degraded or eliminated. A second experiment showed that in objectively defined grouping tasks, subjects grouped faster by illusory figures than by inducing elements. These results indicate that grouping can occur after illusory contours have been perceived.

Responding to children's disclosure of familial abuse: what survivors tell us.

This study is based on the reports of 384 adults who were abused physically, sexually, and/or emotionally in childhood by family members. It describes the survivors' attempts, as children, to get help by disclosing the abuse to someone who might intervene; those who did not disclose explain their reasons. The results indicate that disclosure usually did not bring an end to the abuse, and that little action was taken to control the perpetrator, even after disclosure took place. The responses received by the children to their disclosure are linked to their levels of self-esteem and family functioning as adults.

Color, consciousness, and the isomorphism constraint.

The relations among consciousness, brain behavior, and scientific explanation are explored in the domain of color perception. Current scientific knowledge about color similarity, color composition, dimensional structure, unique colors, and color categories is used to assess Locke's "inverted spectrum argument" about the undetectability of color transformations. A symmetry analysis of color space shows that the literal interpretation of this argument--reversing the experience of a rainbow--would not work. Three other color to color transformations might work, however, depending on the relevance of certain color categories. The approach is then generalized to examine behavioral detection of arbitrary differences in color experiences, leading to the formulation of a principled distinction, called the "isomorphism constraint," between what can and cannot be determined about the nature of color experience by objective behavioral means. Finally, the prospects for achieving a biologically based explanation of color experience below the level of isomorphism are considered in light of the limitations of behavioral methods. Within-subject designs using biological interventions hold the greatest promise for scientific progress on consciousness, but objective knowledge of another person's experience appears impossible. The implications of these arguments for functionalism are discussed.

Normal mode oscillation in the presence of inhomogeneous broadening.

We investigate effects of inhomogeneous broadening of excitons on normal mode oscillation in semiconductor microcavities using a coupled oscillator model. We show that inhomogeneous broadening can drastically alter the coherent oscillatory energy exchange process even in regimes where normal mode splitting remains nearly unchanged. The depth, frequency, and phase of normal mode oscillations of excitons at a given energy within the inhomogeneous distribution depend strongly on the energy separation between the exciton and the normal mode resonance. In addition, for an inhomogeneous broadened system, pronounced oscillations in the intensity of the optical field or the total induced optical polarization no longer imply a similar oscillatory coherent energy exchange between excitons and cavity photons.

Genetics, phenotype, and natural history of autosomal dominant cyclic hematopoiesis.

Cyclic hematopoiesis, (CH, or cyclic neutropenia) is a rare disease manifested by transient severe neutropenia that recurs approximately every 21 days. The hematologic profile of families with the autosomal dominant form (ADCH) has not been well characterized, and it is unknown if the phenotype is distinct from the more common sporadic congenital or acquired forms of CH. We studied nine ADCH families whose children displayed typical CH blood patterns. Pedigrees confirmed dominant inheritance without evidence of heterogeneity or decreased penetrance; three pedigrees suggested new mutations. Families were Caucasian with exception of one with a Cherokee Native American founder: A wide spectrum of symptom severity, ranging from asymptomatic to life-threatening illness, was observed within families. The phenotype changed with age. Children displayed typical neutrophil cycles with symptoms of mucosal ulceration, lymphadenopathy, and infections. Adults often had fewer and milder chronic neutropenia without distinct cycles. While CH is commonly described as "benign", four children in three of the nine families died of Clostridium or E. coli colitis, documenting the need for urgent evaluation of abdominal pain. Misdiagnosis with other neutropenias was common but can be avoided by serial blood counts in index cases. Genetic counseling requires specific histories and complete blood counts in relatives at risk to assess status regardless of symptoms, especially to determine individuals with new mutations. We propose diagnostic criteria for ADCH in affected children and adults. Recombinant human granulocyte colony-stimulating factor treatment resulted in dramatic improvement of neutropenia and morbidity. The differential diagnosis from other forms of familial neutropenia is reviewed.

Instrumentation and techniques for carbon dioxide lasers in equine general surgery.

The carbon dioxide laser has become an important surgical instrument in human and veterinary medicine. The unique properties of this laser make it the instrument of choice for precise incision, coagulation, and vaporization of tissue at the body surface with minimal morbidity to the patient. This article describes the instrumentation and techniques used to perform a variety of equine general surgical procedures with the carbon dioxide laser. The benefits of surgery using the carbon dioxide laser include precise dissection with minimal trauma to adjacent tissues, good hemostasis, and the ability of the laser beam's thermal properties to kill bacteria or tumor cells in the operative field.

Remembering the earthquake: direct experience vs. hearing the news.

Three groups of informants--two in California, one in Atlanta--recalled their experiences of the 1989 Loma Prieta earthquake shortly after the event and again 11/2 years later. The Californians' recalls of their own earthquake experiences were virtually perfect. Even their recalls of hearing the news of an earthquake-related event were very good: much higher than Atlantan recalls of hearing about the quake itself. Atlantans who had relatives in the affected area remembered significantly more than those who did not. These data show that personal involvement in the quake led to greatly improved recall, but do not show why. Many Californian informants reported low levels of stress/arousal during the event; arousal ratings were not significantly correlated with recall. The authors suggest that repeated narrative rehearsals may have played an important role.

Late influences on perceptual grouping: Amodal completion.

Perceptual grouping is generally assumed to be an early visual process that operates on a previously unorganized image-based representation. The present experiment shows that elements perceived as occluded by a closer surface tend to be grouped with elements having the same shape as the amodally completed percept rather than with those having the same retinal shape as the incomplete stimulus. It is therefore concluded that perceptual grouping by shape similarity either occurs after amodal completion or is a temporally extended process that occurs both before and after it.

Suspensory ligament desmitis.

The gross and functional anatomy of the suspensory ligament (SL) and its ultrasonographic variability are described. Injuries of the suspensory apparatus are divided into lesions confined to the proximal one third of the metacarpus or metatarsus (proximal suspensory desmitis and avulsion fractures), lesions of the body, and branch lesions. Complete breakdown injuries are also discussed. In view of the close association of the SL, the second, third, and fourth metacarpal or metatarsal bones, and the proximal sesamoid bones, associated bony lesions are also considered.

Restoration of urban waterways and vacant areas: the first steps toward sustainability.

Increased population pressure and human activities have significantly altered the effectiveness of functions of ecosystems ("ecosystem services") at the local and regional scale. Of primary importance is the decrease in water quality due to urban storm water runoff. A number of communities have initiated restoration strategies to improve water quality standards. One such strategy is the incorporation of riparian walkways with native flora. As a result of such restoration efforts, habitats for native fauna have improved, and the number and diversity of wildlife have increased in urban settings. Restoration of urban habitats also provides social and economic benefits to the surrounding community. Efforts to mitigate the loss of ecological resources by restoring native habitats on lots that cannot be developed or on abandoned lots hold a high, unrealized potential. Habitat restoration not only provides natural diversions to urban surroundings, but also enlightens and educates individual citizens about the importance of balanced ecosystems and the role of humans within ecosystems. Education is the primary step toward creating ecologically sustainable communities.