Poverty indicators and mental health functioning among adults living with HIV in Delhi, India.

Poor mental health functioning among persons living with HIV (PLHIV) has gained considerable attention particularly in low-income countries that disproportionately carry the global HIV/AIDS burden. Fewer studies, however, have examined the relationship between poverty indicators and mental health among PHLIV in India. Based on this cross-sectional study of 196 HIV-seropositive adults who received medical services at Shalom AIDS Project in Delhi, India, structural equation modeling and mediation analysis were employed to estimate the associations between poverty indices (household asset index, food security, unemployment, water treatment, sanitation), HIV-health factors (illness in the past 3 months, co-morbid medical conditions), and psychological distress. In the final model, ownership of fewer household assets was associated with higher levels of food insecurity, which in turn was associated with higher psychological distress. Also, the household asset index, food insecurity, and unemployment had a larger effect on psychological distress than new opportunistic infections. These findings build on increasing evidence that support concerted efforts to design, evaluate, and refine HIV mental health interventions that are mainstreamed with livelihood programming in high poverty regions in India.

Primary motor cortical discharge during force field adaptation reflects muscle-like dynamics.

We often make reaching movements having similar trajectories within very different mechanical environments, for example, with and without an added load in the hand. Under these varying conditions, our kinematic intentions must be transformed into muscle commands that move the limbs. Primary motor cortex (M1) has been implicated in the neural mechanism that mediates this adaptation to new movement dynamics, but our recent experiments suggest otherwise. We have recorded from electrode arrays that were chronically implanted in M1 as monkeys made reaching movements under two different dynamic conditions: the movements were opposed by either a clockwise or counterclockwise velocity-dependent force field acting at the hand. Under these conditions, the preferred direction (PD) of neural discharge for nearly all neurons rotated in the direction of the applied field, as did those of proximal limb electromyograms (EMGs), although the median neural rotation was significantly smaller than that of muscles. For a given neuron, the rotation angle was very consistent, even across multiple sessions. Within the limits of measurement uncertainty, both the neural and EMG changes occurred nearly instantaneously, reaching a steady state despite ongoing behavioral adaptation. Our results suggest that M1 is not directly involved in the adaptive changes that occurred within an experimental session. Rather, most M1 neurons are directly related to the dynamics of muscle activation that themselves reflect the external load. It appears as though gain modulation, the differential recruitment of M1 neurons by higher motor areas, can account for the load and behavioral adaptation-related changes in M1 discharge.

Statistical assessment of the stability of neural movement representations.

In systems neuroscience, neural activity that represents movements or sensory stimuli is often characterized by spatial tuning curves that may change in response to training, attention, altered mechanics, or the passage of time. A vital step in determining whether tuning curves change is accounting for estimation uncertainty due to measurement noise. In this study, we address the issue of tuning curve stability using methods that take uncertainty directly into account. We analyze data recorded from neurons in primary motor cortex using chronically implanted, multielectrode arrays in four monkeys performing center-out reaching. With the use of simulations, we demonstrate that under typical experimental conditions, the effect of neuronal noise on estimated preferred direction can be quite large and is affected by both the amount of data and the modulation depth of the neurons. In experimental data, we find that after taking uncertainty into account using bootstrapping techniques, the majority of neurons appears to be very stable on a timescale of minutes to hours. Lastly, we introduce adaptive filtering methods to explicitly model dynamic tuning curves. In contrast to several previous findings suggesting that tuning curves may be in constant flux, we conclude that the neural representation of limb movement is, on average, quite stable and that impressions to the contrary may be largely the result of measurement noise.

The number of axillary nodes removed as a predictor of regional recurrence in node negative breast cancer.

PURPOSE: To determine if the number of axillary nodes removed is a predictor of recurrence in node negative breast cancer. MATERIALS AND METHODS: Five hundred thirty-six patients with T1-T2, N0 invasive breast cancer, treated with lumpectomy and axillary node dissection (AND), were reviewed from January 1, 1986 to December 31, 1992. Patients received radiation to whole breast only, without regional nodal radiation. There was no adjuvant chemotherapy or Tamoxifen given. Patients were grouped according to the number of axillary nodes dissected as follows: 1-5 nodes (91 patients), 6-10 nodes (225 patients) and > 10 nodes (220 patients). Hazard ratios and p-values were determined for time to local recurrence, regional recurrence and for disease specific survival. RESULTS: Median follow-up was 11.2 years. The overall local recurrence and regional recurrence rates for the three groups were: 1-5 nodes, 9.9% and 8.8%, respectively, 6-10 nodes, 10.2% and 2.2%, respectively, and > 10 nodes, 11.8% and 2.7%, respectively. The effect of number of axillary nodes removed was statistically significant only for regional recurrence (p = 0.017). There was no adverse effect on disease specific survival (p = 0.363). CONCLUSION: The number of axillary nodes removed predicts only for regional recurrence in node negative breast cancer patients, with less than 6 nodes removed associated with higher regional recurrence. This may have clinical implications with the current practice of sentinel node biopsy (SNB) replacing axillary node dissection in early stage breast cancer.

Incidence of neural tube defects in the least-developed area of India: a population-based study.

Hospital-based records from major cities of India, where roughly a quarter of the population resides, identified the frequency of neural tube defects (NTDs) as ranging from 3.9 to 8.8 per 1000 births, but the incidence in rural areas is unknown. We did a population-based door-to-door survey of mothers living in remote clusters of villages in Balrampur District in Uttar Pradesh, a region ranked as the least-developed area in India. The data showed that the incidence of NTDs was 6.57-8.21 per 1000 livebirths, which is among the highest worldwide. India's Ministry of Health needs to produce a strategy to reduce the incidence of such defects.

Eleven-year follow-up results in the delay of breast irradiation after conservative breast surgery in node-negative breast cancer patients.

PURPOSE: This retrospective review was conducted to determine if delay in the start of radiotherapy after conservative breast surgery had any detrimental effect on local recurrence or disease-free survival in node-negative breast cancer patients. METHODS AND MATERIALS: A total of 568 patients with T1 and T2, N0 breast cancer were treated with breast-conserving surgery and breast irradiation, without adjuvant systemic therapy, between January 1, 1985 and December 31, 1992 at the London Regional Cancer Centre. The time intervals from definitive breast surgery to breast irradiation used for analysis were 0 to 8 weeks (201 patients), greater than 8 to 12 weeks (235 patients), greater than 12 to 16 weeks (91 patients), and greater than 16 weeks (41 patients). Kaplan-Meier estimates of time to local-recurrence and disease-free survival rates were calculated. RESULTS: Median follow-up was 11.2 years. Patients in all 4 time intervals were similar in terms of age and pathologic features. No statistically significant difference was seen between the 4 groups in local recurrence or disease-free survival with surgery radiotherapy interval (p = 0.521 and p = 0.222, respectively). The overall local-recurrence rate at 5 and 10 years was 4.6% and 11.3%, respectively. The overall disease-free survival at 5 and 10 years was 79.6% and 67.0%, respectively. CONCLUSION: This retrospective study suggests that delay in the start of breast irradiation of up to 16 weeks from definitive surgery does not increase the risk of recurrence in node-negative breast cancer patients. The certainty of these results is limited by the retrospective nature of this analysis.

The effect of timing of radiotherapy after breast-conserving surgery in patients with positive or close resection margins, young age, and node-negative disease, with long term follow-up.

PURPOSE: The aim of this study was to determine the effect of timing of radiotherapy after conservative breast surgery on local recurrence in women with positive resection margins and young age, treated without systemic therapy. METHODS AND MATERIALS: A total of 568 patients with T1 and T2, N0 breast cancer were treated with breast-conserving surgery and breast irradiation, between January 1, 1985, and December 31, 1992, at the London Regional Cancer Centre. 63 patients (11.1%) had positive/close resection margins (< 2 mm) and 48 patients (8.4%) were age < or = 40 years. For patients with positive resection margins, the time intervals from breast surgery to breast irradiation used for analysis were, 0 to 8 weeks, > 8 to 12 weeks and > 12 weeks. For patients < or = 40 years, the intervals used for analysis were 0 to 8 weeks and > 8 weeks. RESULTS: Median follow up was 11.2 years. For patients < or = 40 years, local recurrence rate at 5 and 10 years was 17.2% and 19.8% respectively. Four patients (17.4%) treated in the 0-week to 8-week interval and 7 patients (28.0%) treated in the > 8 week interval had local recurrences. For patients < or = 40 years with positive resection margins, the local recurrence rate was 25.0%. For patients with positive resection margins, 5-year and 10-year local recurrence rates were as follows: 0 to 8 weeks, 0% and 10.5% respectively; > 8 to 12 weeks, 10.3% and 10.3% respectively; and > 12 weeks, 13.3% and 20.0% respectively. CONCLUSION: Patients < or = 40 years have an increased local recurrence rate which occurs early. Patients with positive resection margins have higher local recurrence rates that become apparent when breast irradiation is delayed.

Expression of osteopontin and HGF/met in adult soft tissue tumors.

There is a need for molecular markers that predict biological behavior of adult soft tissue tumors. Elevated levels of osteopontin (OPN) a transformation-linked protein, have been associated with poor survival in many cancers. OPN induces cell migration in cancer cells, in part through activation of the hepatocyte growth factor (HGF) receptor (Met) and its signaling pathway. Met expression has been associated with a poor prognosis in some sarcomas. In a series of 15 patients with adult soft tissue tumors, we found that mRNA levels of OPN (p=0.015), Met (p=0.03) and HGF (p<0.001) were significantly higher in tumor tissues relative to paired normal tissues. By immunohistochemistry, in tumor tissue from 33 patients, we demonstrated that increased expression of OPN, but not Met protein, was associated with higher stage (p=0.025) and grade (p=0.005). We found that increased expression of OPN, but not Met protein, was associated with decreased overall survival (p=0.008) at five years. This study, which is the first to examine coexpression of these two markers, suggests that OPN may have potential as a prognostic marker in adult soft tissue sarcomas, and further that OPN+/-Met signaling pathways may contribute to their biological behavior.

Time interval from breast-conserving surgery to breast irradiation in early stage node-negative breast cancer: 17-year follow-up results and patterns of recurrence.

PURPOSE: A retrospective chart review was conducted to determine whether the time interval from breast-conserving surgery to breast irradiation (surgery-radiation therapy interval) in early stage node-negative breast cancer had any detrimental effects on recurrence rates. METHODS AND MATERIALS: There were 566 patients with T1 to T3, N0 breast cancer treated with breast-conserving surgery and breast irradiation and without adjuvant systemic treatment between 1985 and 1992. The surgery-to-radiation therapy intervals used for analysis were 0 to 8 weeks (201 patients), >8 to 12 weeks (233 patients), >12 to 16 weeks (91 patients), and >16 weeks (41 patients). Kaplan-Meier estimates of time to local recurrence, disease-free survival, distant disease-free survival, cause-specific survival, and overall survival rates were calculated. RESULTS: Median follow-up was 17.4 years. Patients in all 4 time intervals were similar in terms of characteristics and pathologic features. There were no statistically significant differences among the 4 time groups in local recurrence (P=.67) or disease-free survival (P=.82). The local recurrence rates at 5, 10, and 15 years were 4.9%, 11.5%, and 15.0%, respectively. The distant disease relapse rates at 5, 10, and 15 years were 10.6%, 15.4%, and 18.5%, respectively. The disease-free failure rates at 5, 10, and 15 years were 20%, 32.3%, and 39.8%, respectively. Cause-specific survival rates at 5, 10, and 15 years were 92%, 84.6%, and 79.8%, respectively. The overall survival rates at 5, 10, and 15 years were 89.3%, 79.2%, and 66.9%, respectively. CONCLUSIONS: Surgery-radiation therapy intervals up to 16 weeks from breast-conserving surgery are not associated with any increased risk of recurrence in early stage node-negative breast cancer. There is a steady local recurrence rate of 1% per year with adjuvant radiation alone.

Effect of interval to definitive breast surgery on clinical presentation and survival in early-stage invasive breast cancer.

PURPOSE: To examine the effect of clinical presentation and interval to breast surgery on local recurrence and survival in early-stage breast cancer. METHODS AND MATERIALS: The data from 397 patients with Stage T1-T2N0 breast carcinoma treated with conservative surgery and breast radiotherapy between 1985 and 1992 were reviewed at the London Regional Cancer Program. The clinical presentation consisted of a mammogram finding or a palpable lump. The intervals from clinical presentation to definitive breast surgery used for analysis were 0-4, >4-12, and >12 weeks. The Kaplan-Meier estimates of the time to local recurrence, disease-free survival, and cause-specific survival were determined for the three groups. Cox regression analysis was used to evaluate the effect of clinical presentation and interval to definitive surgery on survival. RESULTS: The median follow-up was 11.2 years. No statistically significant difference was found in local recurrence as a function of the interval to definitive surgery (p = .424). A significant difference was noted in disease-free survival (p = .040) and cause-specific survival (p = .006) with an interval of >12 weeks to definitive breast surgery. However, the interval to definitive surgery was dependent on the presentation for cause-specific survival, with a substantial effect for patients with a mammographic presentation and a negligible effect for patients with a lump presentation (interaction p = .041). CONCLUSION: The results of this study suggest that an interval of >12 weeks to breast surgery might be associated with decreased survival for patients with a mammographic presentation, but it appeared to have no effect on survival for patients presenting with a palpable breast lump.

Effects of eye position upon activity of neurons in macaque superior colliculus.

We examined the activity of neurons in the deep layers of the superior colliculus of awake behaving rhesus monkeys during the performance of standard oculomotor tasks as well as during self-guided eye movements made while viewing natural images. The standard tasks were used to characterize the activity of neurons based on established criteria. The natural viewing paradigm enabled the sampling of neuronal activity during saccades and fixations distributed over a wide range of eye positions. Two distinct aspects of eye-movement behavior contributed to the modulation of firing activity in these neurons. The well-established influence of saccade amplitude and direction was strongest and most prevalent surrounding the time of the start of the saccade. However, the activity of these neurons was also affected by the orbital position of the eyes, and this effect was best observed during intervals of fixation. Many neurons were sensitive to both parameters, and the directions of their saccade vector and eye position response fields tended to be aligned. The sample of neurons included visual, build-up, and burst activities, alone or in combination. All of these activity types were included in the subpopulation of neurons with significant eye-position tuning, although position tuning was more common in neurons with build-up or burst activity and less common in neurons with visual activity. The presence of both eye-position as well as saccade-vector signals in the superior colliculus is likely important for its role in the planning and guidance of combined movements of the eyes and head.

Modeling unidimensional categorization in monkeys.

The categorization performance of monkeys on a unidimensional perceptual categorization task was examined with reference to decision bound and exemplar theories of categorization. Three rhesus monkeys were presented with stimuli varying along a single dimension, the displacement of a target light from a fixation point. Left or right saccade responses were probabilistically reinforced according to one of three functions, two of which were nonmonotonic at one end of the stimulus space. The monkeys all showed a monotonic increase in response probability as a function of target light displacement in this region, consistent with decision bound theory. Fits of a single-boundary model (GRT, Ashby & Gott, 1988) and two exemplar models--one using a probabilistic response function (GCM; Nosofsky, 1986), the other using a deterministic response function (DEM; Ashby & Maddox, 1993)--revealed overall support for the decision bound model. The results suggest that monkeys used a perceptual decision boundary to perform the task.

A comparison of macaque behavior and superior colliculus neuronal activity to predictions from models of two-choice decisions.

Recently, models in psychology have been shown capable of accounting for the full range of behavioral data from simple two-choice decision tasks: mean reaction times for correct and error responses, accuracy, and the reaction time distributions for correct and error responses. At the same time, recent data from neural recordings have allowed investigation of the neural systems that implement such decisions. In the experiment presented here, neural recordings were obtained from superior colliculus prelude/buildup cells in two monkeys while they performed a two-choice task that has been used in humans for testing psychological models of the decision process. The best-developed psychological model, the diffusion model, and a competing model, the Poisson counter model, were explicitly fit to the behavioral data. The pattern of activity shown in the prelude/buildup cells, including the point at which response choices were discriminated, was matched by the evidence accumulation process predicted from the diffusion model using the parameters from the fits to the behavioral data but not by the Poisson counter model. These results suggest that prelude/buildup cells in the superior colliculus, or cells in circuits in which the superior colliculus cells participate, implement a diffusion decision process or a variant of the diffusion process.