Modulation of auditory responses by modality-specific attention in rat primary auditory cortex

How does attention modulate sensory representations? In order to probe the underlying neural mechanisms, we established a simple rodent model of modality-specific attention. Here we describe results of experiments in freely moving rats in which we have used tetrodes to record neural responses in primary auditory cortex (area A1) while subjects performed this behavior.

Subjects were first trained to perform distinct auditory and olfactory two alternative forced-choice (2AFC) tasks. Training and testing were conducted in a custom three-poke computer-controlled behavioral apparatus. Subjects initiated trials with a center-poke, which triggered presentation of a tone (either 5 or 15 Hz), an odor (either R(-)-2-Octanol or S(+)-2-Octanol), or both. Subjects responded moving to the left or right poke. Correct responses were rewarded with water. Auditory and olfactory blocks (of 50 trials each) were interleaved in a single session. In auditory blocks, pure tones were either presented with or without a null odor (caproic acid, n=2 and 3 respectively), and subjects were cued to perform the task based on auditory stimuli. In olfactory blocks, both odors and pure tones were presented simultaneously, and subjects were cued to perform the task based on olfactory stimuli.

After subjects reached consistent performance on the interleaved blocks, tetrode drives were implanted in primary auditory cortex of the left hemisphere. Single unit responses to tones were heterogeneous, and included transient, sustained, and suppressed. Among 304 responsive units recorded, 19% (58 units) showed modality-specific attentional modulation of at least one of the tone-evoked responses; in most cases, the responses to a particular auditory stimulus was enhanced in the auditory block (or, equivalently, suppressed in the olfactory block). In addition, we also observed modality-specific attentional modulation of the spontaneous activity in similar proportion of units (61 units). 

Our results suggest that shifting attention from audition to olfaction and back can modulate the activity of single neurons in primary auditory cortex

Neural Mechanisms of Selective Auditory Attention in Rats (Dissertation)

How does attention modulate sensory representations? In order to probe the underlying neural mechanisms, we established a simple rodent model of modality-specific attention. Rats were trained to perform distinct auditory two-tone discrimination and olfactory odor discrimination in a two alternative choice (2AC) paradigm. 
To determine auditory cortex’s role in this frequency discrimination task, we used GABA-A receptor agonist muscimol to transiently and reversibly inactivate auditory cortexes bilaterally in rats performing simple interleaved auditory and olfactory discrimination. With olfactory discrimination performance serving as internal control for motivation and decision making capability, we found only auditory two-tone discrimination was selectively impaired in these rats. This shows the auditory cortex is involved in this two-tone discrimination task.
To investigate the neural correlate of modality-specific attention in the auditory cortex, we trained rats to perform interleaved auditory and olfactory blocks (of 50~70 trials each) in a single session. In auditory blocks, pure tones were either presented with or without a neutral odor (caproic acid, n=2 and 3 respectively), and subjects were rewarded for discriminating auditory stimuli. In olfactory blocks, both task odors and pure tones were presented simultaneously, and subjects were rewarded for discriminating olfactory stimuli. We recorded neural responses in primary auditory cortex (area A1) in freely moving rats while subjects performed this behavior. Single unit responses to tones were heterogeneous, and included transient, sustained, and suppressed. We found 205 of 802 units recorded responsive to the stimuli we used. Of these 205 units, 18.5% showed modality-specific attentional modulation of the anticipatory activity before tone onset. In addition, we also observed in smaller proportion of units (11.2%) modality-specific attentional modulation of the tone-evoked responses; in most cases, the responses to a particular auditory stimulus was enhanced in the auditory block (or, equivalently, suppressed in the olfactory block). Attention increased choice probability of the population in the auditory block. We have also observed significant behavior choice probability in small proportions of units. 
Our results suggest that shifting attention between audition to olfaction tasks can modulate the activity of single neurons in primary auditory cortex

Fabrication techniques for very fast diffractive lenses

Aspheric lenses with arbitrary phase functions can be fabricated on thin light weight substrates via the binary optics fabrication technique. However, it is difficult and costly to fabricate a fast lens (f/number less than 1) for use as the shorter wavelengths. The pitch of the masks and the alignment accuracy must be very fine. For a large lens, the space-bandwidth product of the element can also become impractically large. In this paper, two alternate approaches for the fabrication of fast aspheric diffractive lenses are described. The first approach fabricates the diffractive lens interferometrically, utilizing a spherical wavefront to provide the optical power of the lens and a computer generated hologram to create the aspheric components. The second approach fabricates the aspheric diffractive lens in the form if a higher order kinoform which trades groove profile fidelity for coarser feature size. The design and implementation issues for these two fabrication techniques are discussed

Selection of Metastatic Breast Cancer Cells Based on Adaptability of Their Metabolic State

A small subpopulation of highly adaptable breast cancer cells within a vastly heterogeneous population drives cancer metastasis. Here we describe a function-based strategy for selecting rare cancer cells that are highly adaptable and drive malignancy. Although cancer cells are dependent on certain nutrients, e.g., glucose and glutamine, we hypothesized that the adaptable cancer cells that drive malignancy must possess an adaptable metabolic state and that such cells could be identified using a robust selection strategy. As expected, more than 99.99% of cells died upon glutamine withdrawal from the aggressive breast cancer cell line SUM149. The rare cells that survived and proliferated without glutamine were highly adaptable, as judged by additional robust adaptability assays involving prolonged cell culture without glucose or serum. We were successful in isolating rare metabolically plastic glutamine-independent (Gln-ind) variants from several aggressive breast cancer cell lines that we tested. The Gln-ind cells overexpressed cyclooxygenase-2, an indicator of tumor aggressiveness, and they were able to adjust their glutaminase level to suit glutamine availability. The Gln-ind cells were anchorage-independent, resistant to chemotherapeutic drugs doxorubicin and paclitaxel, and resistant to a high concentration of a COX-2 inhibitor celecoxib. The number of cells being able to adapt to non-availability of glutamine increased upon prior selection of cells for resistance to chemotherapy drugs or resistance to celecoxib, further supporting a linkage between cellular adaptability and therapeutic resistance. Gln-ind cells showed indications of oxidative stress, and they produced cadherin11 and vimentin, indicators of mesenchymal phenotype. Gln-ind cells were more tumorigenic and more metastatic in nude mice than the parental cell line as judged by incidence and time of occurrence. As we decreased the number of cancer cells in xenografts, lung metastasis and then primary tumor growth was impaired in mice injected with parental cell line, but not in mice injected with Gln-ind cells

Epidemiological determinants of spread of causal agent of severe acute respiratory syndrome in Hong Kong.

BACKGROUND: Health authorities worldwide, especially in the Asia Pacific region, are seeking effective public-health interventions in the continuing epidemic of severe acute respiratory syndrome (SARS). We assessed the epidemiology of SARS in Hong Kong. METHODS: We included 1425 cases reported up to April 28, 2003. An integrated database was constructed from several sources containing information on epidemiological, demographic, and clinical variables. We estimated the key epidemiological distributions: infection to onset, onset to admission, admission to death, and admission to discharge. We measured associations between the estimated case fatality rate and patients' age and the time from onset to admission. FINDINGS: After the initial phase of exponential growth, the rate of confirmed cases fell to less than 20 per day by April 28. Public-health interventions included encouragement to report to hospital rapidly after the onset of clinical symptoms, contact tracing for confirmed and suspected cases, and quarantining, monitoring, and restricting the travel of contacts. The mean incubation period of the disease is estimated to be 6.4 days (95% CI 5.2-7.7). The mean time from onset of clinical symptoms to admission to hospital varied between 3 and 5 days, with longer times earlier in the epidemic. The estimated case fatality rate was 13.2% (9.8-16.8) for patients younger than 60 years and 43.3% (35.2-52.4) for patients aged 60 years or older assuming a parametric gamma distribution. A non-parametric method yielded estimates of 6.8% (4.0-9.6) and 55.0% (45.3-64.7), respectively. Case clusters have played an important part in the course of the epidemic. INTERPRETATION: Patients' age was strongly associated with outcome. The time between onset of symptoms and admission to hospital did not alter outcome, but shorter intervals will be important to the wider population by restricting the infectious period before patients are placed in quarantine

Transmission dynamics of the etiological agent of SARS in Hong Kong: impact of public health interventions.

We present an analysis of the first 10 weeks of the severe acute respiratory syndrome (SARS) epidemic in Hong Kong. The epidemic to date has been characterized by two large clusters-initiated by two separate "super-spread" events (SSEs)-and by ongoing community transmission. By fitting a stochastic model to data on 1512 cases, including these clusters, we show that the etiological agent of SARS is moderately transmissible. Excluding SSEs, we estimate that 2.7 secondary infections were generated per case on average at the start of the epidemic, with a substantial contribution from hospital transmission. Transmission rates fell during the epidemic, primarily as a result of reductions in population contact rates and improved hospital infection control, but also because of more rapid hospital attendance by symptomatic individuals. As a result, the epidemic is now in decline, although continued vigilance is necessary for this to be maintained. Restrictions on longer range population movement are shown to be a potentially useful additional control measure in some contexts. We estimate that most currently infected persons are now hospitalized, which highlights the importance of control of nosocomial transmission

Avian Influenza Risk Perception, Hong Kong

A telephone survey of 986 Hong Kong households determined exposure and risk perception of avian influenza from live chicken sales. Householders bought 38,370,000 live chickens; 11% touched them when buying, generating 4,220,000 exposures annually; 36% (95% confidence interval [CI] 33%–39%) perceived this as risky, 9% (7%–11%) estimated >50% likelihood of resultant sickness, whereas 46% (43%–49%) said friends worried about such sickness. Recent China travel (adjusted odds ratio 0.35; CI 0.13–0.91), traditional beliefs (1.20, 1.06–1.13), willingness to change (0.29, 0.11–0.81) and believing cooking protects against avian influenza (8.66, 1.61-46.68) predicted buying. Birth in China (2.79, 1.43–5.44) or overseas (4.23, 1.43–12.53) and unemployment (3.87, 1.24–12.07) predicted touching. Age, avian influenza contagion worries, husbandry threat, avian influenza threat, and avian influenza anxiety predicted perceived sickness risk. High population exposures to live chickens and low perceived risk are potentially important health threats in avian influenza

Modification by Influenza on Health Effects of Air Pollution in Hong Kong

Background: Both influenza viruses and air pollutants have been well documented as major hazards to human health, but few epidemiologic studies have assessed effect modification of influenza on health effects of ambient air pollutants. Objectives: We aimed to assess modifying effects of influenza on health effects of ambient air pollutants. Methods: We applied Poisson regression to daily numbers of hospitalizations and mortality to develop core models after adjustment for potential time-varying confounding variables. We assessed modification of influenza by adding variables for concentrations of single ambient air pollutants and proportions of influenza-positive specimens (influenza intensity) and their cross-product terms. Results: We found significant effect modification of influenza (p < 0.05) for effects of ozone. When influenza intensity is assumed to increase from 0% to 10%, the excess risks per 10-μg/m 3 increase in concentration of O 3 increased 0.24% and 0.40% for hospitalization of respiratory disease in the all-ages group and ≥ 65 year age group, respectively; 0.46% for hospitalization of acute respiratory disease in the all-ages group; and 0.40% for hospitalization of chronic obstructive pulmonary disease in the ≥ 65 group. The estimated increases in the excess risks for mortality of respiratory disease and chronic obstructive pulmonary disease in the all-ages group were 0.59% and 1.05%, respectively. We found no significant modification of influenza on effects of other pollutants in most disease outcomes under study. Conclusions: Influenza activity could be an effect modifier for the health effects of air pollutants particularly for O 3 and should be considered in the studies for short-term effects of air pollutants on health.published_or_final_versio

Preliminary results of trial NPC-0501 evaluating the therapeutic gain by changing from concurrent-adjuvant to induction-concurrent chemoradiotherapy, changing from fluorouracil to capecitabine, and changing from conventional to accelerated radiotherapy fractionation in patients with locoregionally advanced nasopharyngeal carcinoma

© 2014 American Cancer Society. BACKGROUND A current recommendation for locoregionally advanced nasopharyngeal carcinoma (NPC) is conventional fractionated radiotherapy with concurrent cisplatin plus adjuvant cisplatin and fluorouracil (PF). In this randomized trial, the authors evaluated the potential therapeutic benefit from changing to an induction-concurrent chemotherapy sequence, replacing fluorouracil with oral capecitabine, and/or using accelerated rather than conventional radiotherapy fractionation. METHODS Patients with stage III through IVB, nonkeratinizing NPC were randomly allocated to 1 of 6 treatment arms. The protocol was amended in 2009 to permit confining randomization to the conventional fractionation arms. The primary endpoint was progression-free survival. Secondary endpoints included overall survival and safety. RESULTS In total, 803 patients were accrued, and 706 patients were randomly allocated to all 6 treatment arms. Comparisons of induction PF versus adjuvant PF did not indicate a significant improvement. Unadjusted comparisons of induction cisplatin and capecitabine (PX) versus adjuvant PF indicated a favorable trend in progression-free survival for the conventional fractionation arm (P = .045); analyses that were adjusted for other significant factors and fractionation reflected a significant reduction in the hazards of disease progression (hazard ratio [HR], 0.54; 95% confidence interval [CI], 0.36-0.80) and death (HR, 0.42; 95% CI, 0.25-0.70). Unadjusted comparisons of induction sequences versus adjuvant sequences did not reach statistical significance, but adjusted comparisons indicated favorable improvements by induction sequence. Comparisons of induction PX versus induction PF revealed fewer toxicities (neutropenia and electrolyte disturbance), unadjusted comparisons of efficacy were statistically insignificant, but adjusted analyses indicated that induction PX had a lower hazard of death (HR, 0.57; 95% CI, 0.34-0.97). Changing the fractionation from conventional to accelerated did not achieve any benefit but incurred higher toxicities (acute mucositis and dehydration). CONCLUSIONS Preliminary results indicate that the benefit of changing to an induction-concurrent sequence remains uncertain; replacing fluorouracil with oral capecitabine warrants further validation in view of its convenience, favorable toxicity profile, and favorable trends in efficacy; and accelerated fractionation is not recommended for patients with locoregionally advanced NPC who receive chemoradiotherapy.postprin