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BACKGROUND: The current standard of care in locally advanced rectal cancer (LARC) is neoadjuvant long-course chemoradiotherapy (nCRT) followed by total mesorectal excision (TME). Surgery is conventionally performed approximately 6-8 weeks after nCRT. This study aimed to determine the effect on outcomes of extending this interval. METHODS: A systematic search was performed for studies reporting oncological results that compared the classical interval (less than 8 weeks) from the end of nCRT to TME with a minimum 8-week interval in patients with LARC. The primary endpoint was the rate of pathological complete response (pCR). Secondary endpoints were recurrence-free survival, local recurrence and distant metastasis rates, R0 resection rates, completeness of TME, margin positivity, sphincter preservation, stoma formation, anastomotic leak and other complications. A meta-analysis was performed using the Mantel-Haenszel method. RESULTS: Twenty-six publications, including four RCTs, with 25 445 patients were identified. A minimum 8-week interval was associated with increased odds of pCR (odds ratio (OR) 1·41, 95 per cent c.i. 1·30 to 1·52; P < 0·001) and tumour downstaging (OR 1·18, 1·05 to 1·32; P = 0·004). R0 resection rates, TME completeness, lymph node yield, sphincter preservation, stoma formation and complication rates were similar between the two groups. The increased rate of pCR translated to reduced distant metastasis (OR 0·71, 0·54 to 0·93; P = 0·01) and overall recurrence (OR 0·76, 0·58 to 0·98; P = 0·04), but not local recurrence (OR 0·83, 0·49 to 1·42; P = 0·50). CONCLUSION: A minimum 8-week interval from the end of nCRT to TME increases pCR and downstaging rates, and improves recurrence-free survival without compromising surgical morbidity.

ANTECEDENTES: El tratamiento estándar actual del cáncer de recto localmente avanzado (locally advanced rectal cancer, LARC) consiste en quimiorradioterapia neoadyuvante de ciclo largo (neoadjuvant, long-course chemoradiation, nCRT) seguida de exéresis total del mesorrecto (total mesorectal excision, TME). De forma convencional, la cirugía se realiza a las 6-8 semanas después de la nCRT. Este estudio tuvo como objetivo determinar el efecto sobre los resultados de ampliar este intervalo. MÉTODOS: Se realizó una búsqueda sistemática de los estudios que analizaban los resultados oncológicos, comparando el intervalo clásico (< 8 semanas) desde el final de la nCRT hasta la TME con un intervalo mínimo de 8 semanas, en pacientes con LARC. El criterio de valoración principal fue la tasa de respuesta patológica completa (pathologic complete response, pCR). Los criterios de valoración secundarios fueron las tasas de supervivencia sin recidiva (recurrence-free survival, RFS), recidiva local (local recurrence, LR) y metástasis a distancia (distant metastasis, DM), tasas de resección R0, integridad (completeness) del mesorrecto, afectación del margen de resección, preservación esfinteriana, formación de estoma, fuga anastomótica y otras complicaciones. Se realizó un metaanálisis utilizando el método de Mantel-Haenszel. RESULTADOS: Se identificaron 26 publicaciones, incluidos cuatro ensayos clínicos aleatorizados, con 17.220 pacientes. Un intervalo mínimo de 8 semanas se asoció con un aumento de la razón de oportunidades (odds ratio, OR) de pCR (OR, 1,68, i.c. del 95% 1,37-2,06, P < 0,001) y de disminución del estadio tumoral (OR 1,18, i.c. del 95% 1,05-1,32, P = 0,004). Los porcentajes de resección R0, integridad del mesorrecto, ganglios linfáticos identificados, preservación esfinteriana, formación de estoma y complicaciones fueron similares entre los dos grupos. El aumento del porcentaje de pCR se tradujo en una disminución de las DM (OR 0,71, i.c. del 95% 0,54-0,93, P = 0,01) y de la recidiva global (OR 0,76, i.c. del 95% 0,58-0,98, P = 0,04), pero no de la LR (OR 0,83, i.c. del 95% 0,49-1,42, P = 0,50). CONCLUSIÓN: Un intervalo mínimo de 8 semanas entre el final de la nCRT y la TME aumenta las tasas de pCR y la reducción del estadio tumoral, así como mejora la RFS sin comprometer la morbilidad quirúrgica.

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We measured particulate matter (PM), acrolein, and other indoor air contaminants in eight visits to grocery stores in California. Retail stores of other types (hardware, furniture, and apparel) were also sampled on additional visits. Based on tracer gas decay data, most stores had adequate ventilation according to minimum ventilation rate standards. Grocery stores had significantly higher concentrations of acrolein, fine and ultrafine PM, compared to other retail stores, likely attributable to cooking. Indoor concentrations of PM2.5 and acrolein exceeded health guidelines in all tested grocery stores. Acrolein emission rates to indoors in grocery stores had a mean estimate about 30 times higher than in other retail store types. About 80% of the indoor PM2.5 measured in grocery stores was emitted indoors, compared to only 20% for the other retail store types. Calculations suggest a substantial increase in outdoor air ventilation rate by a factor of three from current level is needed to reduce indoor acrolein concentrations. Alternatively, acrolein emission to indoors needs to be reduced 70% by better capturing of cooking exhaust. To maintain indoor PM2.5 below the California annual ambient standard of 12 µg/m(3) , grocery stores need to use air filters with an efficiency rating higher than the MERV 8 air filters commonly used today.

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This research assesses benefits of adding to California Title-24 ventilation rate (VR) standards a performance-based option, similar to the American Society of Heating, Refrigerating, and Air Conditioning Engineers 'Indoor Air Quality Procedure' (IAQP) for retail spaces. Ventilation rates and concentrations of contaminants of concern (CoC) were measured in 13 stores. Mass balance models were used to estimate 'IAQP-based' VRs that would maintain concentrations of all CoCs below health- or odor-based reference concentration limits. An intervention study in a 'big box' store assessed how the current VR, the Title 24-prescribed VR, and the IAQP-based VR (0.24, 0.69, and 1.51 air changes per hour) influenced measured IAQ and perceived of IAQ. Neither current VRs nor Title 24-prescribed VRs would maintain all CoCs below reference limits in 12 of 13 stores. In the big box store, the IAQP-based VR kept all CoCs below limits. More than 80% of subjects reported acceptable air quality at all three VRs. In 11 of 13 buildings, saving energy through lower VRs while maintaining acceptable IAQ would require source reduction or gas-phase air cleaning for CoCs. In only one of the 13 retail stores surveyed, application of the IAQP would have allowed reduced VRs without additional contaminant-reduction strategies.

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UNLABELLED: Ventilation rates (VRs) in buildings must adequately control indoor levels of pollutants; however, VRs are constrained by the energy costs. Experiments in a simulated office assessed the effects of VR per occupant on perceived air quality (PAQ), Sick Building Syndrome (SBS) symptoms, and decision-making performance. A parallel set of experiments assessed the effects of VR per unit floor area on the same outcomes. Sixteen blinded healthy young adult subjects participated in each study. Each exposure lasted four hours and each subject experienced two conditions in a within-subject study design. The order of presentation of test conditions, day of testing, and gender were balanced. Temperature, relative humidity, VRs, and concentrations of pollutants were monitored. Online surveys assessed PAQ and SBS symptoms and a validated computer-based tool measured decision-making performance. Neither changing the VR per person nor changing the VR per floor area, had consistent statistically significant effects on PAQ or SBS symptoms. However, reductions in either occupant-based VR or floor-area-based VR had a significant and independent negative impact on most decision-making measures. These results indicate that the changes in VR employed in the study influence performance of healthy young adults even when PAQ and SBS symptoms are unaffected. PRACTICAL IMPLICATIONS: The study results indicate the importance of avoiding low VRs per person and low VRs per floor area to minimize decrements in cognitive performance.

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UNLABELLED: This field study measured ventilation rates and indoor air quality in 21 visits to retail stores in California. Three types of stores, such as grocery, furniture/hardware stores, and apparel, were sampled. Ventilation rates measured using a tracer gas decay method exceeded the minimum requirement of California's Title 24 Standard in all but one store. Concentrations of volatile organic compounds (VOCs), ozone, and carbon dioxide measured indoors and outdoors were analyzed. Even though there was adequate ventilation according to standard, concentrations of formaldehyde and acetaldehyde exceeded the most stringent chronic health guidelines in many of the sampled stores. The whole-building emission rates of VOCs were estimated from the measured ventilation rates and the concentrations measured indoor and outdoor. Estimated formaldehyde emission rates suggest that retail stores would need to ventilate at levels far exceeding the current Title 24 requirement to lower indoor concentrations below California's stringent formaldehyde reference level. Given the high costs of providing ventilation, effective source control is an attractive alternative. PRACTICAL IMPLICATIONS: Field measurements suggest that California retail stores were well ventilated relative to the minimum ventilation rate requirement specified in the Building Energy Efficiency Standards Title 24. Concentrations of formaldehyde found in retail stores were low relative to levels found in homes but exceeded the most stringent chronic health guideline. Looking ahead, California is mandating zero energy commercial buildings by 2030. To reduce the energy use from building ventilation while maintaining or even lowering formaldehyde in retail stores, effective formaldehyde source control measures are vitally important.

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UNLABELLED: Ultraviolet photocatalytic oxidation (UVPCO) systems for removal of volatile organic compounds (VOCs) from air are being considered for use in office buildings. Here, we report an experimental evaluation of a UVPCO device with tungsten oxide modified titanium dioxide (TiO2) as the photocatalyst. The device was challenged with complex VOC mixtures. One mixture contained 27 VOCs characteristic of office buildings and another comprised 10 VOCs emitted by cleaning products, in both cases at realistic concentrations (low ppb range). VOC conversion efficiencies varied widely, usually exceeded 20%, and were as high as approximately 80% at about 0.03 s residence time. Conversion efficiency generally diminished with increased airflow rate, and followed the order: alcohols and glycol ethers > aldehydes, ketones, and terpene hydrocarbons > aromatic and alkane hydrocarbons > halogenated aliphatic hydrocarbons. Conversion efficiencies correlated with the Henry's law constant more closely than with other physicochemical parameters. An empirical model based on the Henry's law constant and the gas-phase reaction rate with hydroxyl radical provided reasonable estimates of pseudo-first order photocatalytic reaction rates. Formaldehyde, acetaldehyde, acetone, formic acid and acetic acid were produced by the device due to incomplete mineralization of common VOCs. Formaldehyde outlet/inlet concentration ratios were in the range 1.9-7.2. PRACTICAL IMPLICATIONS: Implementation of air cleaning technologies for both VOCs and particles in office buildings may improve indoor air quality, or enable indoor air quality levels to be maintained with reduced outdoor air supply and concomitant energy savings. One promising air cleaning technology is ultraviolet photocatalytic oxidation (UVPCO) air cleaning. For the prototype device evaluated here with realistic mixtures of VOCs, conversion efficiencies typically exceeded the minimum required to counteract predicted VOC concentration increases from a 50% reduction in ventilation. However, the device resulted in the net generation of formaldehyde and acetaldehyde from the partial oxidation of ubiquitous VOCs. Further development of the technology is needed to eliminate these hazardous air pollutants before such a UVPCO device can be deployed in buildings.

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We recently showed that transport of ergosterol from the ER (endoplasmic reticulum) to the sterol-enriched PM (plasma membrane) in yeast occurs by a non-vesicular (Sec18p-independent) mechanism that results in the equilibration of sterol pools in the two organelles [Baumann, Sullivan, Ohvo-Rekilä, Simonot, Pottekat, Klaassen, Beh and Menon (2005) Biochemistry 44, 5816-5826]. To explore how this occurs, we tested the role of proteins that might act as sterol transporters. We chose to study oxysterol-binding protein homologues (Osh proteins), a family of seven proteins in yeast, all of which contain a putative sterol-binding pocket. Recent structural analyses of one of the Osh proteins [Im, Raychaudhuri, Prinz and Hurley (2005) Nature (London) 437, 154-158] suggested a possible transport cycle in which Osh proteins could act to equilibrate ER and PM pools of sterol. Our results indicate that the transport of newly synthesized ergosterol from the ER to the PM in an OSH deletion mutant lacking all seven Osh proteins is slowed only 5-fold relative to the isogenic wild-type strain. Our results suggest that the Osh proteins are not sterol transporters themselves, but affect sterol transport in vivo indirectly by affecting the ability of the PM to sequester sterols.

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Twenty-seven laboratory experiments were conducted in a simulated smoking room to quantify rates of environmental tobacco smoke (ETS) leakage to a nonsmoking area as a function of the physical and operational characteristics of the smoking room. Data are presented for the various types of leakage flows, the effect of these leaks on smoking room performance and nonsmoker exposure, and the relative importance of each leakage mechanism. The results indicate that the first priority for an effective smoking room is to maintain it depressurized with respect to adjoining nonsmoking areas. The amount of ETS pumped out by the smoking room door when it is opened and closed can be reduced significantly by substituting a sliding door for the standard swing-type door. An "open doorway" configuration used twice the ventilation flow of those with smoking room doors, but yielded less reduction in nonsmoker exposure. Measured results correlated well with results modeled with mass-balance equations (R(2) = 0.82-0.99). Most of these results are based on sulfur hexafluoride (SF(6)) tracer gas leakage. Because five measured ETS tracers showed good correlation with SF(6), these conclusions should apply to ETS leakage as well. Field tests of a designated smoking room in an office building qualitatively agreed with model predictions.

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UNLABELLED: We investigated the relationship between ventilation rates and individual work performance in a call center, and controlled for other factors of the indoor environment. We randomized the position of the outdoor air control dampers, and measured ventilation rate, differential (indoor minus outdoor) carbon dioxide (DeltaCO(2)) concentration, supply air velocity, temperature, humidity, occupant density, degree of under-staffing, shift length, time of day, and time required to complete two different work performance tasks (talking with clients and post-talk wrap-up to process information). DeltaCO(2) concentrations ranged from 13 to 611 p.p.m. We used multivariable regression to model the association between the predictors and the responses. We found that agents performed talk tasks fastest when the ventilation rate was highest, but that the relationship between talk performance and ventilation was not strong or monotonic. We did not find a statistically significant association between wrap-up performance and ventilation rate. Agents were slower at the wrap-up task when the temperature was high (> 25.4 degrees C). Agents were slower at wrap-up during long shifts and when the call center was under-staffed. PRACTICAL IMPLICATIONS: The productivity benefits of ventilation rates that exceed common standards such as ASHRAE Standard 62 may be small (0-2%), and other factors may have a larger impact on productivity. Understaffing and long shifts should be avoided because both showed a negative impact on performance. In this study, high temperature had the largest statistically significant impact on productivity and was caused by occupants fighting over the thermostat setpoint. Care should be taken to avoid high temperatures in call centers. If occupants are allowed to adjust temperature setpoints, then the size and/or duration of the setpoint change should be restricted.

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UNLABELLED: In chamber experiments, we investigated the ventilation effectiveness and thermal comfort of a task ventilation system with an air supply nozzle located underneath the front edge of a desk and directing air towards a heated mannequin or a human volunteer seated at the desk. The task ventilation system provided outside air, while another ventilation system provided additional space cooling but no outside air. Test variables included the vertical angle of air supply (-15 degrees to 45 degrees from horizontal), and the supply flow rate of (3.5-6.5 l/s). Using the tracer gas step-up and step-down procedures, the measured air change effectiveness (i.e., exhaust air age divided by age of air in the breathing zone) in experiments with the mannequin ranged from 1.4 to 2.7 (median, 1.8), whereas with human subjects the air change effectiveness ranged from 1.3 to 2.3 (median, 1.6). The majority of the air change effectiveness values with the human subjects were less than values with the mannequin using comparable tests. Similarly, the tests run with supply air temperature equal to the room air temperature had lower air change effectiveness values than comparable tests with the supply air temperature lower ( approximately 5 degrees C) than the room air temperature. The air change effectiveness values are higher than typically reported for commercially-available task ventilation or displacement ventilation systems. Based on surveys completed by the subjects, operation of the task ventilation system did not cause thermal discomfort. PRACTICAL IMPLICATIONS: With a desk-edge-mounted task ventilation system it is possible to obtain an increase in the effective ventilation rate of 50%. This could lead to reduced energy use. Also, this improvement can be gained while maintaining thermal comfort for occupants. Thus occupants can be thermally comfortable and save energy at the same time.

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OBJECTIVES/HYPOTHESIS: In an effort to reduce operative time, improve diagnostic accuracy, and decrease perioperative morbidity, we combined preoperative technetium Tc 99m-sestamibi localization with the use of the gamma probe intraoperatively. This report examines our experience with the gamma probe for rapid intraoperative localization of parathyroid adenomas. STUDY DESIGN: A retrospective chart review was performed to identify all patients who underwent parathyroid exploration with the aid of the gamma probe at Lenox Hill Hospital (New York, NY). METHODS: Charts were reviewed for operative details, radiological findings, and pathological diagnoses. RESULTS: Between November 1, 1998, and June 30, 2000, 35 parathyroid explorations were performed with the aid of the gamma probe. The preoperative localization study was accurate in 34 of 35 cases. The gamma probe successfully identified the parathyroid adenoma in 33 of 35 cases. There were two false-positive cases in which the gamma probe mistakenly identified a thyroid adenoma rather than a parathyroid adenoma. In 11 of 35 cases, the gamma probe was judged essential for rapid localization of the parathyroid adenoma. These cases included patients with multiple or ectopic adenomas and patients who had previous parathyroid surgery. Average operative time to remove parathyroid disease was 80 minutes (range, 45-140 min), which included 20 to 40 minutes waiting for frozen-section results. All patients became normocalcemic, and there were no major complications in this series. CONCLUSION: The gamma probe is a useful tool that complements a well-performed localization study. It is most useful in patients who have multiple or ectopic adenomas or have had prior parathyroid surgery.

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Epidermal inclusion cyst (EIC) is a recognized cause of an anterior neck mass in children. Controversy exists as to the proper surgical management of an anterior neck EIC: is simple excision adequate treatment, or is a Sistrunk procedure necessary? A retrospective review of the operative logs of the two senior authors (M.M.A., R.F.W.) from 1993 to the present revealed 16 children, ages 6 months to 9 years (mean, 4.5 years), with a diagnosis of anterior neck EIC. An accurate intraoperative diagnosis of an EIC in all cases allowed for a simple excision of the mass rather than a Sistrunk procedure. The final histologic diagnosis was EIC in all 16 patients. Follow-up of these 16 patients for a mean of 4.5 years revealed no recurrences or complications. When the diagnosis of EIC can be made confidently in the operating room, simple excision is an adequate surgical treatment.

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Four open, prospective, postmarketing studies with consistent protocols were undertaken, involving over 25,000 patients and nearly 3600 physicians in four European countries (UK, Netherlands, Germany and Austria). The purpose was to determine the tolerability of terbinafine when prescribed to a large, unselected patient population in general medical practice. Patients were recruited from dermatology departments and from general and family practitioners. All received at least one dose of terbinafine. No specific exclusion criteria were applied. The only treatment instructions provided were those contained in the manufacturer's product information. Patients were monitored for adverse events at baseline, during treatment, and at the end of treatment. Of the 25,884 patients entering the study, 38.6% (9991) had concomitant disease, 42.8% (11,078) were taking other medications, and 22.7% (5876) were older than 60 years. The predominant indication for prescribing terbinafine was onychomycosis. Mean duration of treatment was 13.2 weeks. No adverse events were reported in 89.5% (23,167) of patients. The remaining 10.5% (2717) reported one or more adverse events, primarily gastrointestinal (4.9%) or dermatological (2.3%). A total of 115 serious adverse events were recorded, but of these only four were probably and eight possibly related to terbinafine. There were no reported drug-drug interactions, even in patients receiving concomitant medications metabolized by cytochrome P-450 enzymes. There were also no clinically significant drug-disease interactions. In conclusion, terbinafine is well tolerated in an unselected general practice population. This confirms its good tolerability previously established during controlled clinical trials.

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In laboratory experiments, we investigated two task/ambient conditioning systems with air supplied from desk-mounted air outlets to efficiently ventilate the breathing zone of heated manikins seated at desks. In most experiments, the task conditioning systems provided outside air while a conventional ventilation system provided additional space cooling but no outside air. Air change effectiveness (i.e., exhaust air age divided by age of air at the manikin's face) was measured with a tracer gas step-up procedure. Other tracer gases simulated the release of pollutants from nearby occupants and from the floor covering, and the associated pollutant removal efficiencies (i.e., exhaust air concentrations divided by concentrations at manikin's face) were calculated. High values of air change effectiveness (approximately 1.3 to 1.9) and high values of pollutant removal efficiency (approximately 1.2 to 1.6) were measured when these task conditioning systems supplied 100% outdoor air at a flow rate of 7 to 9 L s-1 per occupant. Air change effectiveness was reasonably well correlated with the pollutant removal efficiency. Overall, the experimental data suggest that these task/ambient conditioning systems can be used to improve ventilation and air quality or to save energy while maintaining a typical level of IAQ at the breathing zone.

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1. The safety profile of terbinafine, the first orally active allylamine, was monitored in the UK in a post-marketing setting. The study recruited 10,361 patients, a number which is approximately 5% of the population who received oral terbinafine in the UK during the period of the study. 2. Follow-up data were available on 9,879 patients. During the course of the study 14.5% patients reported medical events. 49% were thought to be possibly or probably related to terbinafine treatment. Seventy-four of the events (< 1%) were classified as 'serious' and of these only five were assessed as possibly or probably related to treatment. 3. Taste disturbance occurred in 0.6% of the patients and emerged as the only new adverse reaction probably attributable to terbinafine: this was significantly commoner in females and reversible on stopping treatment, with a median time to recovery of 42 days. 4. The study approach successfully combined hospital based dermatology outpatient and general practice centres. Source data verification was conducted on 13% of the cohort selected randomly. 5. Overall, the denominator-based description of the safety profile in actual practice shows terbinafine to be well-tolerated against a wide background of age and coexisting illness.

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The mammalian cerebral cortex is divided into functionally distinct areas. Although radial patterns of neuronal migration have been thought to be essential for patterning these areas, direct observation of migrating cells in cortical brain slices has revealed that cells follow both radial and nonradial pathways as they travel from their sites of origin in the ventricular zone out to their destinations in the cortical plate (O'Rourke, N.A., Dailey, M.E., Smith, S.J. and McConnell, S.K. (1992) Science 258, 299-302). These findings suggested that neurons may not be confined to radial migratory pathways in vivo. Here, we have examined the patterns of neuronal migration in the intact cortex. Analysis of the orientations of [3H]thymidine-labeled migrating cells suggests that nonradial migration is equally common in brain slices and the intact cortex and that it increases during neurogenesis. Additionally, cells appear to follow nonradial trajectories at all levels of the developing cerebral wall, suggesting that tangential migration may be more prevalent than previously suspected from the imaging studies. Immunostaining with neuron-specific antibodies revealed that many tangentially migrating cells are young neurons. These results suggest that tangential migration in the intact cortex plays a pivotal role in the tangential dispersion of clonally related cells revealed by retroviral lineage studies (Walsh, C. and Cepko, C. L. (1992) Science 255, 434-440). Finally, we examined possible substrata for nonradial migration in dorsal cortical regions where the majority of glia extend radially. Using confocal and electron microscopy, we found that nonradially oriented cells run perpendicular to glial processes and make glancing contacts with them along their leading processes. Thus, if nonradial cells utilize glia as a migratory substratum they must glide across one glial fiber to another. Examination of the relationships between migratory cells and axons revealed axonal contacts with both radial and nonradial cells. These results suggest that nonradial cells use strategies and substrata for migration that differ from those employed by radial cells.

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1. The ocular hypotensive effect of 0.025% bromocriptine and 0.25% timolol eye drops was compared in nine healthy human volunteers, using non-contact tonometry. 2. Considering all post-dosing measurements compared with placebo and including the baseline values as continuous independent variables, using multiple linear regression analysis, both bromocriptine and timolol had a significant ocular hypotensive effect (P less than 0.0001) in the treated eye with a significant but lesser effect in the contralateral eye. 3. In the concentrations used, timolol was more efficacious than bromocriptine in lowering intraocular pressure (P less than 0.025). 4. Using other forms of vehicles for bromocriptine to improve efficacy and studying the ocular hypotensive effect of topical application of other dopamine-2-receptor agonists such as pergolide and lisuride was suggested.

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