Neutron scattering and neural-network quantum molecular dynamics investigation of the vibrations of ammonia along the solid-to-liquid transition.

Vibrational spectroscopy allows us to understand complex physical and chemical interactions of molecular crystals and liquids such as ammonia, which has recently emerged as a strong hydrogen fuel candidate to support a sustainable society. We report inelastic neutron scattering measurement of vibrational properties of ammonia along the solid-to-liquid phase transition with high enough resolution for direct comparisons to ab-initio simulations. Theoretical analysis reveals the essential role of nuclear quantum effects (NQEs) for correctly describing the intermolecular spectrum as well as high energy intramolecular N-H stretching modes. This is achieved by training neural network models using ab-initio path-integral molecular dynamics (PIMD) simulations, thereby encompassing large spatiotemporal trajectories required to resolve low energy dynamics while retaining NQEs. Our results not only establish the role of NQEs in ammonia but also provide general computational frameworks to study complex molecular systems with NQEs.

An Evidence-Based Initiative to Reduce Alarm Fatigue in a Burn Intensive Care Unit.

BACKGROUND: Alarm fatigue occurs when nurses are exposed to multiple alarms of mixed significance and become desensitized to alarms to the point that a critical alarm may receive no response or a delayed response. In burn intensive care units, reducing the risk of alarm fatigue is uniquely challenging because of the critically ill patient population and the nature of burn skin injuries. Nurses and the interdisciplinary team can become fatigued and desensitized to alarms, decreasing response rates for necessary interventions. OBJECTIVE: To decrease the risk of alarm fatigue by using an initiative designed to reduce nonactionable and false alarms in a burn intensive care unit. METHODS: Baseline data (alarm count per patient-day by alarm type) were collected for 1 month before education and implementation of evidence-based interventions. Data were collected every 6 months for 2 years. INTERVENTIONS: A series of interventions included raising awareness of the risks associated with alarm fatigue, customizing alarm parameters and default settings, providing education on electrode placement and daily electrode changes, using physical reminders, and consistently sharing alarm data. The education, delivered in modules, aligned with the evidence-based interventions. RESULTS: Preintervention baseline data were compared to postintervention data at 6, 12, 18, and 24 months. The results showed a significantly sustained reduction (P < .001) in total alarm rate over time. CONCLUSION: A quality improvement initiative based on evidence-based practice can contribute to a sustainable reduction in nonactionable and false alarms, ultimately improving patient safety.

Development of the Low Emissions Analysis Platform - Integrated Benefits Calculator (LEAP-IBC) tool to assess air quality and climate co-benefits: Application for Bangladesh.

Low- and middle-income countries have the largest health burdens associated with air pollution exposure, and are particularly vulnerable to climate change impacts. Substantial opportunities have been identified to simultaneously improve air quality and mitigate climate change due to overlapping sources of greenhouse gas and air pollutant emissions and because a subset of pollutants, short-lived climate pollutants (SLCPs), directly contribute to both impacts. However, planners in low- and middle-income countries often lack practical tools to quantify the air pollution and climate change impacts of different policies and measures. This paper presents a modelling framework implemented in the Low Emissions Analysis Platform - Integrated Benefits Calculator (LEAP-IBC) tool to develop integrated strategies to improve air quality, human health and mitigate climate change. The framework estimates emissions of greenhouse gases, SLCPs and air pollutants for historical years, and future projections for baseline and mitigation scenarios. These emissions are then used to quantify i) population-weighted annual average ambient PM2.5 concentrations across the target country, ii) household PM2.5 exposure of different population groups living in households cooking using different fuels/technologies and iii) radiative forcing from all emissions. Health impacts (premature mortality) attributable to ambient and household PM2.5 exposure and changes in global average temperature change are then estimated. This framework is applied in Bangladesh to evaluate the air quality and climate change benefits from implementation of Bangladesh's Nationally Determined Contribution (NDC) and National Action Plan to reduce SLCPs. Results show that the measures included to reduce GHGs in Bangladesh's NDC also have substantial benefits for air quality and human health. Full implementation of Bangladesh's NDC, and National SLCP Plan would reduce carbon dioxide, methane, black carbon and primary PM2.5 emissions by 25%, 34%, 46% and 45%, respectively in 2030 compared to a baseline scenario. These emission reductions could reduce population-weighted ambient PM2.5 concentrations in Bangladesh by 18% in 2030, and avoid approximately 12,000 and 100,000 premature deaths attributable to ambient and household PM2.5 exposures, respectively, in 2030. As countries are simultaneously planning to achieve the climate goals in the Paris Agreement, improve air quality to reduce health impacts and achieve the Sustainable Development Goals, the LEAP-IBC tool provides a practical framework by which planners can develop integrated strategies, achieving multiple air quality and climate benefits.

Disruption in murine Eml1 perturbs retinal lamination during early development.

During mammalian development, establishing functional neural networks in stratified tissues of the mammalian central nervous system depends upon the proper migration and positioning of neurons, a process known as lamination. In particular, the pseudostratified neuroepithelia of the retina and cerebrocortical ventricular zones provide a platform for progenitor cell proliferation and migration. Lamination defects in these tissues lead to mispositioned neurons, disrupted neuronal connections, and abnormal function. The molecular mechanisms necessary for proper lamination in these tissues are incompletely understood. Here, we identified a nonsense mutation in the Eml1 gene in a novel murine model, tvrm360, displaying subcortical heterotopia, hydrocephalus and disorganization of retinal architecture. In the retina, Eml1 disruption caused abnormal positioning of photoreceptor cell nuclei early in development. Upon maturation, these ectopic photoreceptors possessed cilia and formed synapses but failed to produce robust outer segments, implying a late defect in photoreceptor differentiation secondary to mislocalization. In addition, abnormal positioning of Müller cell bodies and bipolar cells was evident throughout the inner neuroblastic layer. Basal displacement of mitotic nuclei in the retinal neuroepithelium was observed in tvrm360 mice at postnatal day 0. The abnormal positioning of retinal progenitor cells at birth and ectopic presence of photoreceptors and secondary neurons upon maturation suggest that EML1 functions early in eye development and is crucial for proper retinal lamination during cellular proliferation and development.

Erlotinib in African Americans with advanced non-small cell lung cancer: a prospective randomized study with genetic and pharmacokinetic analyses.

Prospective studies on epidermal growth factor receptor (EGFR) inhibitors in African Americans with non-small cell lung cancer (NSCLC) have not previously been performed. In this phase II randomized study, 55 African Americans with NSCLC received 150 mg/day erlotinib or a body weight-adjusted dose with subsequent escalations to the maximum-allowable dose, 200 mg/day, to achieve rash. Erlotinib and OSI-420 exposures were lower than those observed in previous studies, consistent with CYP3A pharmacogenetics implying higher metabolic activity. Tumor genetics showed only two EGFR mutations, EGFR amplification in 17/47 samples, eight KRAS mutations, and five EML4-ALK translocations. Although absence of rash was associated with shorter time to progression (TTP), disease-control rate, TTP, and 1-year survival were not different between the two dose groups, indicating the dose-to-rash strategy failed to increase clinical benefit. Low incidence of toxicity and low erlotinib exposure suggest standardized and maximum-allowable dosing may be suboptimal in African Americans.

Nerve-sparing subcapsular resection of head and neck schwannomas: technique evaluation and literature review.

BACKGROUND: The head and neck region harbours crucial structures and hence the surgical technique used to remove schwannomas from this region should cause minimal damage to these structures, with complete removal of pathology. METHODS: This study entailed a retrospective analysis of 10 patients with head and neck schwannomas that were excised using a nerve-sparing subcapsular dissection technique. The primary aims were to assess the functional impact of the surgical technique on the structure of origin and to evaluate local control. RESULTS: One patient with parapharyngeal schwannoma developed symptoms suggestive of 'first bite syndrome' in the late post-operative period. Another patient with facial nerve schwannoma had House-Brackmann grade II weakness in the immediate post-operative period, which subsequently resolved. None of the patients developed recurrence during a median follow-up period of two years. CONCLUSION: The nerve-sparing subcapsular dissection technique provided effective local control of tumour pathology, with relative preservation of neural function post-operatively.

Global air quality and health co-benefits of mitigating near-term climate change through methane and black carbon emission controls.

BACKGROUND: Tropospheric ozone and black carbon (BC), a component of fine particulate matter (PM ≤ 2.5 µm in aerodynamic diameter; PM(2.5)), are associated with premature mortality and they disrupt global and regional climate. OBJECTIVES: We examined the air quality and health benefits of 14 specific emission control measures targeting BC and methane, an ozone precursor, that were selected because of their potential to reduce the rate of climate change over the next 20-40 years. METHODS: We simulated the impacts of mitigation measures on outdoor concentrations of PM(2.5) and ozone using two composition-climate models, and calculated associated changes in premature PM(2.5)- and ozone-related deaths using epidemiologically derived concentration-response functions. RESULTS: We estimated that, for PM(2.5) and ozone, respectively, fully implementing these measures could reduce global population-weighted average surface concentrations by 23-34% and 7-17% and avoid 0.6-4.4 and 0.04-0.52 million annual premature deaths globally in 2030. More than 80% of the health benefits are estimated to occur in Asia. We estimated that BC mitigation measures would achieve approximately 98% of the deaths that would be avoided if all BC and methane mitigation measures were implemented, due to reduced BC and associated reductions of nonmethane ozone precursor and organic carbon emissions as well as stronger mortality relationships for PM(2.5) relative to ozone. Although subject to large uncertainty, these estimates and conclusions are not strongly dependent on assumptions for the concentration-response function. CONCLUSIONS: In addition to climate benefits, our findings indicate that the methane and BC emission control measures would have substantial co-benefits for air quality and public health worldwide, potentially reversing trends of increasing air pollution concentrations and mortality in Africa and South, West, and Central Asia. These projected benefits are independent of carbon dioxide mitigation measures. Benefits of BC measures are underestimated because we did not account for benefits from reduced indoor exposures and because outdoor exposure estimates were limited by model spatial resolution.

Pilot trial of IOM duty hour recommendations in neurology residency programs: unintended consequences.

OBJECTIVE: To study the potential effect of the 2008 Institute of Medicine (IOM) work duty hour (WDH) recommendations on neurology residency programs. METHODS: This study evaluated resident sleepiness, personal study hours, quality of life, and satisfaction and faculty satisfaction during a control month using the Accreditation Council for Graduate Medical Education WDH requirements and during an intervention month using the IOM WDH recommendations. Resident participation in both schedules was mandatory, but both resident and faculty participation in the outcome measures was voluntary. RESULTS: Thirty-four residents (11 postgraduate year [PGY]-4, 9 PGY-3, and 14 PGY-2) participated. End-of-work shift sleepiness, mean weekly sleep hours, personal study hours, and hours spent in lectures did not differ between the control and intervention months. Resident quality of life measured by the Maslach Burnout Inventory declined for 1 subscore in the intervention month (p = 0.03). Resident education satisfaction declined during the intervention month for issues related to continuity of care, patient hand-offs, and knowledge of their patients. Faculty satisfaction declined during the intervention month, without a decline in quality of life. CONCLUSIONS: The results from 3 residency programs suggest that the IOM WDH recommendations may negatively affect neurology resident education. This study was limited by the short duration of implementation, negative bias against the IOM recommendations, and inability to blind faculty. Additional study of the IOM WDH recommendations is warranted before widespread implementation.

N deposition as a threat to the World's protected areas under the Convention on Biological Diversity.

This paper combines the world's protected areas (PAs) under the Convention on Biological Diversity (CBD), common classification systems of ecosystem conservation status, and current knowledge on ecosystem responses to nitrogen (N) deposition to determine areas most at risk. The results show that 40% (approx. 11% of total area) of PAs currently receive >10 kg N/ha/yr with projections for 2030 indicating that this situation is not expected to change. Furthermore, 950 PAs are projected to receive >30 kg N/ha/yr by 2030 (approx. twice the 2000 number), of which 62 (approx. 11,300 km(2)) are also Biodiversity Hotspots and G200 ecoregions; with forest and grassland ecosystems in Asia particularly at risk. Many of these sites are known to be sensitive to N deposition effects, both in terms of biodiversity changes and ecosystem services they provide. Urgent assessment of high risk areas identified in this study is recommended to inform the conservation efforts of the CBD.

Soil sensitivity to acidification in Asia: status and prospects.

Exceedance of steady-state critical loads for soil acidification is consistently found in southern China and parts of SE Asia, but there is no evidence of impacts outside of China. This study describes a methodology for calculating the time to effects for soils sensitive to acidic deposition in Asia under potential future sulfur (S), nitrogen (N), and calcium (Ca) emission scenarios. The calculations are matched to data availability in Asia to produce regional-scale maps that provide estimates of the time (y) it will take for soil base saturation to reach a critical limit of 20% in response to acidic inputs. The results show that sensitive soil types in areas of South, Southeast, and East Asia, including parts of southern China, Burma, Hainan, Laos, Thailand, Vietnam, and the Western Ghats of India, may acidify to a significant degree on a 0-50 y timescale, depending on individual site management and abiotic and biotic characteristics. To make a clearer assessment of risk, site-specific data are required for soil chemistry and deposition (especially base cation deposition); S and N retention in soils and ecosystems; and biomass harvesting and weathering rates from sites across Asia representative of different soil and vegetation types and management regimes. National and regional assessments of soils using the simple methods described in this paper can provide an appreciation of the time dimension of soil acidification-related impacts and should be useful in planning further studies and, possibly, implementing measures to reduce risks of acidification.

Primary adenocarcinoma of cervical esophagus.

Most upper esophageal malignancies are squamous cell carcinomas, rarely adenocarcinomas arising from Barrett's esophagus and very rarely adenocarcinomas from heterotopic gastric mucosa without evidence of Barrett's especially in the cervical part of the esophagus. We report a case of adenocarcinoma of the polypoid type in the upper esophagus (cervical esophagus) arising from ectopic gastric mucosa, in a 60 year-old man who presented with progressive dysphagia. Accurate diagnosis by esophagogram revealed a large mass in the cervical esophagus; CAT scan showed intraluminal mass at the level of thoracic inlet, esophagogastroscopy showed a fleshy polyp (3.2cm x 3.0cm) at 20 cm from the incisors with a biopsy confirming moderately differentiated adenocarcinoma with no evidence of Barrett's esophagus. Through a left cervical approach and resection of medial third of clavicle, the tumor was removed by partial esophagectomy followed by lymph node dissection, and proved to be T1NOMO, stage I (AJCC staging 6th ed.). Post operatively, the patient received chemoradiation with no evidence of recurrence or metastasis in six years of follow up. It seems this tumor has a much better prognosis than adenocarcinomas arising from Barrett's. To our knowledge only 19 cases have been reported in literature so far.

Alms1-disrupted mice recapitulate human Alström syndrome.

Mutations in the human ALMS1 gene cause Alström syndrome (AS), a progressive disease characterized by neurosensory deficits and by metabolic defects including childhood obesity, hyperinsulinemia and Type 2 diabetes. Other features that are more variable in expressivity include dilated cardiomyopathy, hypertriglyceridemia, hypercholesterolemia, scoliosis, developmental delay and pulmonary and urological dysfunctions. ALMS1 encodes a ubiquitously expressed protein of unknown function. To obtain an animal model in which the etiology of the observed pathologies could be further studied, we generated a mouse model using an Alms1 gene-trapped ES cell line. Alms1-/- mice develop features similar to patients with AS, including obesity, hypogonadism, hyperinsulinemia, retinal dysfunction and late-onset hearing loss. Insulin resistance and increased body weight are apparent between 8 and 12 weeks of age, with hyperglycemia manifesting at approximately 16 weeks of age. In addition, Alms1-/- mice have normal hearing until 8 months of age, after which they display abnormal auditory brainstem responses. Diminished cone ERG b-wave response is observed early, followed by the degeneration of photoreceptor cells. Electron microscopy revealed accumulation of intracellular vesicles in the inner segments of photoreceptors, whereas immunohistochemical analysis showed mislocalization of rhodopsin to the outer nuclear layer. These findings suggest that ALMS1 has a role in intracellular trafficking.

Human papilloma virus testing knowledge and attitudes among women attending colposcopy clinic with ASCUS/LGSIL pap smears.

OBJECTIVE: To study women's knowledge regarding the role of human papilloma virus (HPV) in cervical intraepithelial neoplasia and their attitudes toward the integration of HPV testing as part of routine follow-up of atypical squamous cell of uncertain significance/low-grade squamous intraepithelial lesion (ASCUS/LGSIL) abnormalities. METHODS: Over a 12-month period, all women attending the University of Ottawa colposcopy clinic for evaluation and follow-up of ASCUS/LGSIL Pap smears were recruited. Demographic data included age, nature of the Pap smear abnormality, gravidity, parity, occupation and education level, smoking history, previous history of abnormal smears, colposcopic examination and treatment, and current method of contraception. The women were asked to rate their level of concern over their Pap smear abnormality, from 0 (not concerned) to 10 (very concerned). Women's knowledge regarding the role of HPV in cervical intraepithelial neoplasia and the rationale behind the use of HPV testing was assessed by the clinic nurse as being minimal, moderate, or good, as defined by pre-specified criteria. Upon explanation by the nurses of the results of the recent ALTS (ASCUS/LGSIL Triage Study) trial, the women were asked to state whether they preferred to continue with regular colposcopic surveillance every 6 months, or to use the results of the HPV test, if negative, to reduce the number of colposcopy examinations to one annually. Descriptive statistics and logistic regression analysis were used to identify significant demographic factors associated with the women's preference for incorporation of HPV testing in their follow-up. All P values less than.10 were considered to be statistically significant, due to the exploratory nature of the study. RESULTS: Of the 100 women who participated in the study, 42% presented with ASCUS. The mean age (+/- SD) of the women was 33.63 +/- 11.25 years (range, 18-75 years); 66% were office workers with at least a community college degree, 86% reported previous abnormal Pap smears, and 67% had previously been seen for colposcopy. Fifty-eight percent of the women rated their concern level as being 6 or more, while 15% ranked their concerns as maximal at 10. In terms of knowledge about HPV, 75% of the women had no or very minimal knowledge of the role of HPV in cervical intraepithelial neoplasia. With regard to HPV testing, 84% of the study group had either never heard of the test or had only a minimal knowledge of HPV testing. After being informed of the ALTS results, 64% of the women chose to use HPV testing to help in triaging the needs for frequent colposcopy. Logistic regression modelling showed that a college level education (odds ratio [OR], 2.27; 95% confidence interval [CI], 0.95-;5.45; P =.06) and history of previous treatment for abnormal Pap smears (OR, 3.31; CI, 0.88- 12.46; P =.07) were closely associated with the adoption of HPV testing in clinical management. CONCLUSION: There exists a significant lack of knowledge about HPV and its role in the pathogenesis of cervical intraepithelial neoplasia. Women who have received previous treatments for cervical intraepithelial neoplasia and those with college-level educations were more likely to adopt this new technology as part of their care.

Simultaneously presenting head and neck and lung cancer: a diagnostic and treatment dilemma.

OBJECTIVES/HYPOTHESIS: Synchronous tumors are defined as malignancies presenting within 6 months of the index tumors. A significant subset of patients present at initial evaluation with malignant tumors of both the head and neck (head and neck squamous cell carcinoma) and the lung, which are termed simultaneous primaries. The management and treatment outcomes in this cohort of patients have not been clearly defined and are the subject of the present review. STUDY DESIGN: Retrospective chart review of previously untreated patients. METHODS: From January 1974 to December 1997, a total of 2964 patients were treated for mucosal squamous cell carcinoma of the head and neck. Forty-two patients fulfilled the criteria for synchronous head and neck and lung malignancy. Of these, 27 patients had simultaneous tumors of the head and neck and the lung. This cohort of patients (n = 27) was stratified into three treatment groups. Patients in group A (n = 10) had resectable head and neck and lung primaries treated with curative intent. Group B (n = 8) was composed of patients who could have been treated with curative intent but declined and were given only palliative therapy. Patients in group C (n = 9) were candidates for only palliative treatment. RESULTS: The estimated 5-year disease-specific survival in group A was 47%, whereas patients in group B had a 5-year disease-specific survival of only 13% (P =.05). There were no survivors beyond 1 year in group C. The presence of mediastinal adenopathy in patients in group A portended poor clinical outcome. There was an estimated 5-year disease-specific survival of 51% in patients with no preoperative evidence of mediastinal adenopathy (n = 7), whereas 67% of patients with radiological evidence of mediastinal adenopathy died (two of three patients). CONCLUSION: The presence of simultaneous head and neck squamous cell carcinoma and pulmonary malignancies should not be a deterrent to aggressive surgical therapy because a potentially satisfactory outcome can be expected in these patients.

Sensate radial forearm free flaps in tongue reconstruction.

BACKGROUND: Successful rehabilitation after ablative surgery requires not only the reconstruction of 3-dimensional form but also the restoration of physiologic function. OBJECTIVE: To assess sensory recovery of reinnervated radial forearm flaps used for tongue reconstruction. PATIENTS AND METHODS: Seventeen patients, who underwent reconstruction of glossectomy defects with reinnervated radial forearm free flaps, formed the study group. Recovery of sensation was measured by both subjective and detailed objective tests 8 months after surgery. Sensory function of the flap was compared with that of the normal residual tongue or the adjacent oral mucosa and the contralateral forearm donor site. RESULTS: All patients involved in this study had tongue defects of hemiglossectomy or greater and adjacent floor of the mouth. Sensory recovery was observed in all of the 17 patients within 8 months. Detailed sensory testing showed that median static 2-point discrimination, moving 2-point discrimination, and pressure sensitivity (1.2 cm, 0.8 cm, and 3.7 psi, respectively) were subjectively greater in the innervated forearm flaps than in the contralateral forearm donor site (2.3 cm, 1.7 cm, and 4.6 psi, respectively) (P= .064) and similar to those of the normal tongue (0.9 cm, 0.5 cm, and 3.6 psi). CONCLUSIONS: In all modalities examined, sensate free flaps proved superior in sensory fidelity to the native forearm donor site and closely approached that of the normal tongue. Microsurgical reinnervation of flaps should be considered in tongue reconstruction.

Cancer of the buccal mucosa: are margins and T-stage accurate predictors of local control?

UNLABELLED: Cancer of the buccal mucosa is an uncommon and aggressive neoplasm of the oral cavity. Less than 2% of patients treated for cancer of the oral cavity at Roswell Park Cancer Institute (RPCI) from 1971 to 1997 had primary buccal cancers. Because the majority of these patients did not undergo any adjuvant treatment, this group provided us with the opportunity to assess the relationship between margin status and local recurrence for both small (T1-T2) and large (T3-T4) tumors treated with surgery alone. MATERIALS AND METHODS: The RPCI tumor registry database reported 104 patients who were treated for buccal carcinoma. A retrospective chart review identified 27 patients who met our criteria for a buccal mucosal primary tumor (epicenter of the mass in the buccal mucosa). There were 13 men and 14 women, ranging in age from 34 to 94 years (mean, 75). Data were collected regarding patient demographics, presenting symptoms, stage, treatment received, and outcome. RESULTS: All patients underwent surgical resection of their primary lesion; 21 (75%) had T1 or T2 tumors. The rate of local recurrence was 56% for the group as a whole. Patients with close or positive margins had a 66% local failure rate as compared with 52% when surgical margins were negative (greater than or equal to 5 mm from the resection margin after tissue fixation; P = ns). Among those in whom negative margins were achieved, patients with T1-T2 disease had a 40% local failure rate with surgical resection alone. CONCLUSIONS: Local excision of T1 and T2 buccal mucosa cancers with pathologically negative margins had a high rate of local recurrence in our series. Low T-stage and negative margins are not adequate predictors of local control. Even early buccal tumors may benefit from adjuvant therapy to enhance local control.

Comparison of trace metals in the intake and discharge water of power plants using "clean" techniques.

Once-through, noncontact condenser cooling water at power plants is frequently discharged back to the fresh or saline water body used for its intake water. This study evaluated the potential effect that trace metals, collected using "clean" sampling and analytical techniques and discharged from a once-through, noncontact cooling water system from a power plant, have on receiving water bodies. A paired t-test was used to compare the intake and discharge concentrations of the metals. The metals analyzed were antimony, arsenic, barium, beryllium, boron, cadmium, chromium, copper, lead, mercury, nickel, selenium, silver, thallium, and zinc. "Clean" is a term applied to field and analytical procedures that are designed to reduce or eliminate ubiquitous metal contamination from samples collected for environmental monitoring. Study results indicate that there is no measurable difference between intake and discharge samples from a noncontact cooling water system, and, therefore, there is no net contribution of metals to receiving water bodies from this system.

Phosphate supplementation for hypophosphataemia and parenteral nutrition.

Routine detection and treatment of acute hypophosphataemia is important in intensive care unit and many other hospitalized patients, but metabolic bone disease and hypophosphataemia are still experienced as a result of parenteral nutrition. A significantly common problem that faces the compounding pharmacist when formulating parenteral nutrition regimens is the difficulty associated with the successful avoidance of calcium phosphate precipitation. Although incorporation of the normal calcium and phosphate requirements into regimens for metabolically stable adults is usually achievable, it can prove impossible in paediatric and neonatal mixtures when using the standard inorganic sources that are currently licensed for use in the UK and USA. In other countries, where organic compounds are routinely available, this problem does not exist.

Risk group-based management of differentiated thyroid carcinoma.

A number of controversies exist in the treatment of differentiated thyroid carcinoma with respect to the extent of surgery, use of radioactive iodine and post-operative thyroxine suppression. Recent recognition of prognostic factors has helped to assign patients, based on their risk profile, as being at high risk of developing recurrence. This has facilitated the development of a selective approach to therapy, thus, avoiding unnecessary treatment and reducing morbidity without compromising treatment outcome. This review attempts to evaluate the current concepts of management of differentiated thyroid carcinoma in the light of these new developments.

Clinical presentation and treatment of non-Hodgkin's lymphoma of the thyroid gland.

BACKGROUND: Non-Hodgkin's lymphoma (NHL) of the thyroid is a rare malignancy. The traditional approach to curative treatment of localized (stages I and II) NHL of the thyroid gland is surgical resection. The recent success of multimodality chemoradiotherapy suggests that surgery should be reserved for providing a tissue diagnosis or relief from acute airway obstruction. It is questionable whether this has made an impact on treatment approaches. METHODS: Retrospective chart review was conducted for all cases of localized NHL of the thyroid gland treated at Roswell Park Cancer Institute between January 1970 and January 1999. RESULTS: Ten patients (8 women, 2 men) with a mean age of 56.8 years were identified. Nine patients (90%) presented with a neck mass; seven patients (70%) had a history of Hashimoto's disease. Nine patients (90%) had extensive investigations to rule out extrathyroidal disease. All patients were treated with either a total thyroidectomy (eight patients) or a thyroid lobectomy (two patients). Nine (90%) were initially treated outside of Roswell Park Cancer Institute and referred secondarily for consideration of further therapy. Adjuvant therapy consisting of cyclophosphamide-based chemoradiotherapy was administered to nine patients. Overall survival was 80% at a mean follow-up of 8.6 years with a disease-specific survival rate of 100%. CONCLUSIONS: A review of the literature suggests that fine needle aspiration (FNA) with flow cytometry and immunohistochemistry can be used to accurately diagnose NHL of the thyroid gland. Open biopsy should be reserved for cases where this technique is not available or where the diagnosis can not be confirmed by FNA alone. Extrathyroidal NHL should be ruled out by chest x-ray, CT scan of the abdomen, and bone marrow biopsy. Further review suggests that the most efficacious therapy is systemic chemotherapy in combination with radiation for local control. Debulking surgery should be used only to provide relief from acute airway obstruction.