SPARC-positive macrophages are the superior prognostic factor in the microenvironment of diffuse large B-cell lymphoma and independent of MYC rearrangement and double-/triple-hit status.

BACKGROUND: Diffuse large B-cell lymphoma (DLBCL) is a heterogeneous disease with respect to outcome. Features of the tumor microenvironment (TME) are associated with prognosis when assessed by gene expression profiling. However, it is uncertain whether assessment of the microenvironment can add prognostic information to the most relevant and clinically well-established molecular subgroups when analyzed by immunohistochemistry (IHC). PATIENTS AND METHODS: We carried out a histopathologic analysis of biomarkers related to TME in a very large cohort (n = 455) of DLBCL treated in prospective trials and correlated with clinicopathologic and molecular data, including chromosomal rearrangements and gene expression profiles for cell-of-origin and TME. RESULTS: The content of PD1+, FoxP3+ and CD8+, as well as vessel density, was not associated with outcome. However, we found a low content of CD68+ macrophages to be associated with inferior progression-free survival (PFS) and overall survival (OS; P = 0.023 and 0.040, respectively) at both univariable and multivariable analyses, adjusted for the factors of the International Prognostic Index (IPI), MYC break and BCL2/MYC and BCL6/MYC double-hit status. The subgroup of PDL1+ macrophages was not associated with survival. Instead, secreted protein acidic and cysteine rich (SPARC)-positive macrophages were identified as the subtype of macrophages most associated with survival. SPARC-positive macrophages and stromal cells directly correlated with favorable PFS and OS (both, P[log rank] <0.001, P[trend] < 0.001). The association of SPARC with prognosis was independent of the factors of the IPI, MYC double-/triple-hit status, Bcl2/c-myc double expression, cell-of-origin subtype and a recently published gene expression signature [lymphoma-associated macrophage interaction signature (LAMIS)]. CONCLUSIONS: SPARC expression in the TME detected by a single IHC staining with fair-to-good interobserver reproducibility is a powerful prognostic parameter. Thus SPARC expression is a strong candidate for risk assessment in DLBCL in daily practice.

Sniffin' Sticks Screening 12 test: Presentation of odours on filter paper improves the recognition rate.

To the Editor: Monitoring of olfactory function and diagnosis of olfactory disorders using the pen-based "Sniffin' Sticks test" is problematic during the SARS-CoV-2 pandemic due to hygienic concerns. The aim of this study was to find out whether the results of olfactory testing obtained by presenting odours on a single-use filter paper is identical to performing the test by presenting the odour pens according to the manufacturer's manual.

Depression, anxiety and quality of life in subjects with atopic eczema in a population-based cross-sectional study in Germany.

BACKGROUND: Atopic eczema (AE) may be associated with several mental health problems. In Germany, existing data from selected patient cohorts may lead to misestimation of the problem. OBJECTIVES: We aimed to cross-sectionally determine associations of AE with depression, anxiety, quality of life (QoL) and social interactions in subjects from the population-based LIFE-Adult-Study. METHODS: Subjects underwent standardized interviews (medical history) and answered standardized questionnaires [Centre of Epidemiologic studies-Depression scale (CES-D), Generalized Anxiety Disorder (GAD-7), Lubben Social Network Scale (LSNS), Short Form Health Survey (SF-8)]. We compared data from subjects with AE with those from subjects with selected other chronic/disabling diseases (cardiovascular, diabetes, cancer) and adjusted for selected sociodemographic parameters. Multivariate binary logistic regression was used for categorical variables, linear regression for continuous variables. RESULTS: Out of 9104 adults included (57% female, median age 54 years), 372 (4.1%) had a history of AE. Compared with controls, subjects with AE showed higher scores for depressive symptoms (9.3% vs. 6.3%; P < 0.001) and anxiety (8.4% vs. 5.6%, P < 0.001). Odds ratio (OR) was 1.5 [CI 1.0; 2.3] (P = 0.031) for depression, which was comparable to OR in patients with a history of cancer (OR 1.6 [1-2.3], P = 0.001. OR for anxiety in AE was 1.5 [1.0; 2.2], P < 0.049, which was slightly higher than in diabetes mellitus (OR 1.2) and stroke (OR 1.4). Other than in diabetes and/or stroke, we did not find a significant association between AE and social isolation. QoL scores were lower in AE than in controls (mean 46.9 vs. 48.0, P < 0.001 for physical and 50.6 vs. 52.5, P < 0.001 for mental components). CONCLUSIONS: Subjects with AE showed higher values for depression and anxiety as well as lower QoL scores compared to controls. With regard to depression, odds in AE and cancer were hardly different. Medical care of AE patients should therefore include mental health evaluation and treatment if indicated.

The age-dependent relationship between resting heart rate variability and functional brain connectivity.

Resting heart rate variability (HRV), an index of parasympathetic cardioregulation and an individual trait marker related to mental and physical health, decreases with age. Previous studies have associated resting HRV with structural and functional properties of the brain - mainly in cortical midline and limbic structures. We hypothesized that aging affects the relationship between resting HRV and brain structure and function. In 388 healthy subjects of three age groups (140 younger: 26.0 ±â€¯4.2 years, 119 middle-aged: 46.3 ±â€¯6.2 years, 129 older: 66.9 ±â€¯4.7 years), gray matter volume (GMV, voxel-based morphometry) and resting state functional connectivity (eigenvector centrality mapping and exploratory seed-based functional connectivity) were related to resting HRV, measured as the root mean square of successive differences (RMSSD). Confirming previous findings, resting HRV decreased with age. For HRV-related GMV, there were no statistically significant differences between the age groups, nor similarities across all age groups. In whole-brain functional connectivity analyses, we found an age-dependent association between resting HRV and eigenvector centrality in the bilateral ventromedial prefrontal cortex (vmPFC), driven by the younger adults. Across all age groups, HRV was positively correlated with network centrality in the bilateral posterior cingulate cortex. Seed-based functional connectivity analysis using the vmPFC cluster revealed an HRV-related cortico-cerebellar network in younger but not in middle-aged or older adults. Our results indicate that the decrease of HRV with age is accompanied by changes in functional connectivity along the cortical midline. This extends our knowledge of brain-body interactions and their changes over the lifespan.

Obesity negatively impacts outcome in elderly female patients with aggressive B-cell lymphomas treated with R-CHOP: results from prospective trials of the German high grade non-Hodgkin's lymphoma trial group.

To study if obesity is a risk factor in elderly patients (>60 years) with aggressive B-cell lymphoma, the outcomes of 576 elderly patients treated with rituximab in the RICOVER-60 trial were analysed in a retrospective study with regard to body mass index (BMI) and gender. Of the 576 patients, 1% had low body weight (BMI < 18·5), 38% were normal weight (18·5 ≤ BMI < 25), 42% were overweight (25 ≤ BMI < 30) and 19% were obese (BMI ≥ 30). Event-free (EFS), progression-free (PFS) and overall survival (OS) according to BMI showed no significant differences for all and for male patients. EFS (P = 0·041), PFS (P = 0·038) and OS (P = 0·031) were significantly better for female non-obese patients. A multivariate analysis adjusted for International Prognostic Index risk factors confirmed these results, with the following hazard ratios (HR) for obesity (BMI ≥ 30) for EFS/PFS/OS: all patients - 1·4/1·4/1·4 (not significant); male patients - 1·2/1·2/1·0 (not significant) and female patients - 1·7 (P = 0·032)/1·9 (P = 0·022)/2·0 (P = 0·017). In conclusion, obesity is a risk factor that influences treatment outcome in elderly female patients with aggressive B-cell lymphoma treated with R-CHOP (rituximab + cyclophosphamide, doxorubicin, vincristine, prednisolone). The inferior outcomes in obese female patients may be due to faster rituximab clearance in obese females.

Optimization of rituximab for the treatment of DLBCL: increasing the dose for elderly male patients.

Male sex is associated with unfavourable pharmacokinetics and prognosis in elderly patients with diffuse large B-cell lymphoma (DLBCL). We investigated higher rituximab doses for elderly male DLBCL patients. Elderly patients (61-80 years) received 6 cycles CHOP-14 (cyclophosphamide, doxorubicin, vincristine and prednisone at 14-day intervals) and were randomized to 8 cycles rituximab (males 500 mg/m2 , females 375 mg/m2 ) every 2 weeks or according to an upfront dose-dense schedule. In 268 (120 females, 148 males) no difference between the standard and the upfront dose-dense rituximab schedule was found (3-year PFS 72% vs. 74%; OS 74% vs. 77%; P = 0.651). The 500 mg/m2 dose of rituximab for male patients was associated with serum levels and exposure times slightly better than in females and a male/female hazard ratio of 0.9 for progression-free survival (PFS) and 0.8 for overall survival. For elderly males, 500 mg/m2 was not more toxic than 375 mg/m2 rituximab, but improved PFS by 32.5% (P = 0.039), with a trend for a (30%) better overall survival (P = 0.076) in a planned subgroup analysis adjusting for International Prognostic Index risk factors. We conclude that the higher rituximab dose for elderly male patients abrogated the adverse prognosis of male sex without increasing toxicity. In the era of personalized medicine, sex-specific pharmacokinetics and toxicities should be investigated for all drugs where these parameters impact on outcome.

Infrared spectra and band strengths of amorphous and crystalline N2O.

Infrared transmission spectra from 4000 to 400 cm-1, and associated band strengths and absorption coefficients, are presented for the first time for both amorphous and crystalline N2O. Changes in the spectra as a function of ice thickness and ice temperature are shown. New measurements of density, refractive index, and specific refraction are reported for amorphous and crystalline N2O. Comparisons are made to published results, and the most-likely reason for some recent disagreements in the literature is discussed. As with CO2, its isoelectronic congener, the formation of amorphous N2O is found to require greater care than the formation of amorphous solids from more-polar molecules.

Nanocolumnar association and domain formation in porous thin films grown by evaporation at oblique angles.

Porous thin films grown at oblique angles by evaporation techniques are formed by tilted nanocolumnar structures which, depending on the material type and growth conditions, associate along certain preferential directions, giving rise to large domains. This arrangement, commonly denoted as bundling association, is investigated in the present work by performing fundamental experiments and growth simulations. It is proved that trapping processes of vapor species at the film surface, together with the shadowing mechanism, mediate the anisotropic widening of the nanocolumns and promote their preferential coalescence along certain directions, giving rise to domains with different shape and size. The role of these two processes is thoroughly studied in connection with the formation of these domains in materials as different as SiO2 and TiO2.

Activation of weak IR fundamentals of two species of astrochemical interest in the T(d) point group--the importance of amorphous ices.

New measurements are reported on the weak ν1 and ν2 fundamentals of frozen CH4, a solid of considerable astrochemical interest. Infrared spectra in the ν1 and ν2 regions are presented for three CH4-ice phases at 10-30 K with new absorption coefficients and band strengths to quantify the results. In contrast to the situation with the two crystalline phases of CH4, both ν1 and ν2 were seen clearly in methane's amorphous phase. To support our CH4 work, we also present new results for NH4SH, a component of Jupiter's atmosphere, showing that the ν2 vibration of NH4(+) undergoes a dramatic loss of intensity during an amorphous-to-crystalline phase transition, but is regenerated in equally-dramatic fashion by radiation-induced amorphization of the sample. Results are compared to work recently published in this journal and elsewhere.

[Gene expression analyses and their possible clinical benefit in head and neck cancer]. / Genexpressionsanalysen und ihrmöglicher klinischer Nutzen inder Betrachtung der Kopf-Hals-Karzinome

Systems biology approaches for mutational (exome analysis and targeted sequencing) and gene expression analysis (transcriptome-wide gene expression profiling) represent a new and growing scientific field in head and neck oncology. In addition to medical biological expertise, bioinformatic assistance is increasingly required. For squamous cell head and neck cancer (HNSCC), the recent molecular genetic single-gene and signal pathway observations represent basic research. Important aspects of this have now been significantly enhanced by systems biology approaches, which have grown into relevant areas of translational clinical research. It is now known that HPV16 is associated with genetic alterations at various locations, but also that it functionally affects genes not altered in their base sequence at the level of methylation. In transcriptome analyses, various consortia found matching clusters of gene expression and HPV16 association with the spectrum of somatic mutations. The differential methylation of gene promoters discovered in HPV16-driven HNSCC proved predictive for survival­even in HNSCC patients without HPV detection. The authors present an overview of some translationally relevant findings and venture an outlook on possible future clinical developments.

Electrostatic interactions of cationic lauric arginate with anionic polysaccharides affect antimicrobial activity against spoilage yeasts.

AIMS: To investigate the effect of anionic polysaccharides often used in beverage applications (xanthan and λ-carrageenan) on the antimicrobial efficacy of the cationic surfactant lauric arginate (LAE) against typical spoilage yeasts. METHODS AND RESULTS: The antimicrobial efficacy of LAE against Saccharomyces cerevisiae, Candida albicans and Zygosaccharomyces bailii in the absence and presence of anionic polysaccharides was assessed by microtitre and macrobroth dilution assays. Combining LAE with either xanthan or λ-carrageenan caused a pronounced decrease in LAE's antimicrobial efficacy, with the minimal inhibitory and lethal concentrations (MIC and MLC) both increasing with increasing polysaccharide concentration. This reduction in antimicrobial efficacy was more pronounced for the addition of λ-carrageenan. To determine the cause of loss of activity, physical properties of solutions were examined. Turbidity and sedimentation measurements indicated that complexes between LAE and anionic polysaccharides had been formed. Electrophoresis measurements showed that complexes had varying electrical charges and dimensions depending on solution composition. CONCLUSION: Results suggest that electrostatic interactions between LAE and anionic polysaccharides play a major role in complex formation and loss of antimicrobial activity. SIGNIFICANCE AND IMPACT OF THE STUDY: Results have important implications for the utilization of LAE as an antimicrobial agent in beverage and food products containing anionic polysaccharides.

Comparison and modelling of pegylated or unpegylated G-CSF schedules in CHOP-14 regimen of elderly patients with aggressive B-cell lymphoma.

Bi-weekly (R)-CHOP therapy is one of the standard treatmentS for elderly patients with aggressive B-cell lymphoma, but it is only feasible with supportive G-CSF treatment. In the trials of the DSHNHL, either unpegylated G-CSF was given daily over 7 or 10 days or pegylated G-CSF was applied at day 4 of each cycle. These schedules were planned on the basis of simulations of a biomathematical pharmacokinetic/pharmacodynamic model. By analysing the observed data, we investigated whether our model predictions were correct and whether even better schedules can be proposed. We used data on 249 matched patients of two prospective trials, RICOVER-60 and PEGFILGRASTIM. The three G-CSF-schedules showed similar outcomes regarding leukocytopenia, infections and days in hospital, with pegylated G-CSF having slightly but not significantly better scores in all three endpoints. Regarding pegylated G-CSF, the best timing is predicted to be any day between days 4 and 7. With respect to unpegylated G-CSF, the starting day is less important, but it should be continued until the end of each cycle.The three G-CSF-schedules are interchangeable in (R)-CHOP-14 for elderly patients with aggressive B-cell lymphoma. Our model correctly predicts time courses of leukocytes. Further model predictions are presented, which can be tested in subsequent clinical trials.

CHO(E)P-14 followed by alemtuzumab consolidation in untreated peripheral T cell lymphomas: final analysis of a prospective phase II trial.

The rate of long-term remissions after treatment of peripheral T cell lymphomas (PTCL) with standard CHOP-like protocols is unsatisfactory. A prospective multicenter phase II trial was initiated in untreated patients with PTCL of all International Prognostic Index-risk groups, evaluating alemtuzumab consolidation in patients with complete or good partial remission after CHO(E)P-14 induction. Twenty-nine (70.7 %) of the 41 enrolled patients received alemtuzumab consolidation (133 mg in total). The main grades 3-4 toxicities during alemtuzumab therapy were infections and neutropenia with one potentially treatment-related death. Complete responses were seen in 58.5 %, partial responses in 2.4 % and 29.3 % had progressive disease. After a median observation time of 46 months, 19 patients have died, 16 of them due to lymphoma and/or salvage therapy complications. Event-free and overall survival at 3 years in the whole intent to treat population are 32.3 and 62.5 %, respectively, and 42.4 and 75.1 % in the patients who received alemtuzumab. In conclusion, application of a short course of alemtuzumab after CHO(E)P-14 induction is feasible although complicated by severe infections. A current phase III trial, applying alemtuzumab as part of the initial chemotherapy protocol to avoid early progression, will further clarify its significance for the therapeutic outcome.

Ventilatory strategies in septic patients. Results from a nationwide observational trial.

BACKGROUND: Mortality in intensive care unit (ICU) patients is affected by multiple variables. The possible impact of the mode of ventilation has not yet been clarified; therefore, a secondary analysis of the "epidemiology of sepsis in Germany" study was performed. The aims were (1) to describe the ventilation strategies currently applied in clinical practice, (2) to analyze the association of the different modes of ventilation with mortality and (3) to investigate whether the ratio between arterial partial pressure of oxygen and inspired fraction of oxygen (PF ratio) and/or other respiratory variables are associated with mortality in septic patients needing ventilatory support. METHODS: A total of 454 ICUs in 310 randomly selected hospitals participated in this national prospective observational 1-day point prevalence of sepsis study including 415 patients with severe sepsis or septic shock according to the American College of Chest Physicians/Society of Critical Care Medicine criteria. RESULTS: Of the 415 patients, 331 required ventilatory support. Pressure controlled ventilation (PCV) was the most frequently used ventilatory mode (70.6 %) followed by assisted ventilation (AV 21.7 %) and volume controlled ventilation (VCV 7.7 %). Hospital mortality did not differ significantly among patients ventilated with PCV (57 %), VCV (71 %) or AV (51 %, p=0.23). A PF ratio equal or less than 300 mmHg was found in 83.2 % of invasively ventilated patients (n=316). In AV patients there was a clear trend to a higher PF ratio (204±70 mmHg) than in controlled ventilated patients (PCV 179±74 mmHg, VCV 175±75 mmHg, p=0.0551). Multiple regression analysis identified the tidal volume to pressure ratio (tidal volume divided by peak inspiratory airway pressure, odds ratio OR=0.94, 95 % confidence interval 95% CI=0.89-0.99), acute renal failure (OR=2.15, 95% CI=1.01-4.55) and acute physiology and chronic health evaluation (APACHE) II score (OR=1.09, 95% CI=1.03-1.15) but not the PF ratio (univariate analysis OR=0.998, 95 % CI=0.995-1.001) as independent risk factors for in-hospital mortality. CONCLUSIONS: This representative survey revealed that severe sepsis or septic shock was frequently associated with acute lung injury. Different ventilatory modes did not affect mortality. The tidal volume to inspiratory pressure ratio but not the PF ratio was independently associated with mortality.

CNS disease in younger patients with aggressive B-cell lymphoma: an analysis of patients treated on the Mabthera International Trial and trials of the German High-Grade Non-Hodgkin Lymphoma Study Group.

BACKGROUND: To describe incidence, risk factors, and influence of treatment on occurrence of central nervous system (CNS) relapse or progression in younger patients with aggressive B-cell lymphoma. PATIENTS AND METHODS: We analyzed 2210 patients with aggressive B-cell lymphoma treated on various studies for CNS relapse/progression. Treatment consisted of CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone) ± etoposide. Six hundred and twenty patients also received rituximab. CNS prophylaxis was intrathecal methotrexate on High-CHOEP and MegaCHOEP phase III studies if upper neck, head, bone marrow, or testes were involved. RESULTS: Fifty-six of 2196 patients (2.6%) developed CNS disease. It occurred early (median 7.0 months), median survival was 5.0 months. Patients with age-adjusted International Prognostic Index (aaIPI) 0 or 1 treated with rituximab showed a low risk for CNS disease (2-year rates: 0% or 0.5%), and rituximab decreased the risk (relative risk 0.3, 95% confidence interval 0.1-0.9, P = 0.029). Patients with aaIPI 2 or 3 showed a moderate risk (4.2%-9.7%) and no significant reduction of CNS disease with rituximab. CNS prophylaxis was of no significant benefit. CONCLUSIONS: In younger patients with aaIPI 0 or 1, CNS relapse/progression is very rare; in patients with aaIPI 2 or 3, the risk is higher (up to 10%) and requires new diagnostic strategies and treatment.

Impact of first- and second-line treatment for Hodgkin's lymphoma on the incidence of AML/MDS and NHL--experience of the German Hodgkin's Lymphoma Study Group analyzed by a parametric model of carcinogenesis.

BACKGROUND: Using a parametric carcinogenesis model, we disentangle the superimposing effects of primary and relapse therapies of Hodgkin's disease on secondary neoplasias. PATIENTS AND METHODS: We analyze eight randomized trials of the German Hodgkin's lymphoma study group [5357 individuals, 67 secondary acute myeloid leukemia (AML)/myelodysplastic syndrome (MDS) and 97 secondary non-Hodgkin's lymphoma (NHL)]. Primary therapies were divided into four groups: radiotherapy alone, moderately dosed COPP/ABVD-like chemotherapies for intermediate and advanced stages and BEACOPP escalated. RESULTS: For secondary AML/MDS, the hazards after primary therapies are proportional (maximum at 3.4 years), while the hazard after relapse therapy is more peaked (maximum at 1.8 years). Intermediate and advanced stage chemotherapy resulted in a cumulative risk of 1.5%, while the risk after BEACOPP escalated is higher (4.4%, P = 0.004) and comparable with that after relapse therapy (4.5%). For secondary NHL, there are no differences in cumulative risk between the primary therapies (2.9%), while the risk after relapse therapy is increased (6.6%, P = 0.002). CONCLUSIONS: BEACOPP escalated moderately increases the risk of secondary AML/MDS but not NHL. No differences were found between other chemotherapies of advanced stages and intermediate stages. Secondary AML/MDS occurs faster after relapse treatment than after primary treatment.

Primary mediastinal B-cell lymphoma treated with CHOP-like chemotherapy with or without rituximab: results of the Mabthera International Trial Group study.

BACKGROUND: The aim of this subgroup analysis of the Mabthera International Trial Group study was to evaluate the impact of chemotherapy and rituximab in primary mediastinal B-cell lymphoma (PMBCL) in comparison to other diffuse large B-cell lymphoma (DLBCL). METHODS: Patients were randomly assigned to six cycles of CHOP-like regimens with or without rituximab. RESULTS: Of 824 patients enrolled, 87 had PMBCL and 627 other types of DLBCL. Rituximab increased the rates of complete remission (unconfirmed) in both PMBCL (from 54% to 80%, P = 0.015) and DLBCL (from 72% to 87%, P < 0.001). In PMBCL, rituximab virtually eliminated progressive disease (PD) (2.5% versus 24%, P < 0.001), whereas without rituximab, PD was more frequent in PMBCL than in DLBCL (24% versus 10%, P = 0.010). With a median observation time of 34 months, 3-year event-free survival (EFS) was improved by rituximab for PMBCL (78% versus 52%, P = 0.012) and for DLBCL (81% versus 61%, P < 0.001). Overall survival benefit was similar for DLBCL (93% versus 85%, P < 0.001) and PMBCL (89% versus 78%, P = 0.158). CONCLUSION: In young patients with PMBCL (age-adjusted International Prognostic Index 0-1), rituximab added to six cycles of CHOP-like chemotherapy increases response rate and EFS to the same extent as other DLBCL. The combination of rituximab with CHOP chemotherapy is an effective treatment in PMBCL with good prognosis features.

Randomized comparison of pegfilgrastim day 4 versus day 2 for the prevention of chemotherapy-induced leukocytopenia.

BACKGROUND: To study the effects of deferring pegfilgrastim until day 4 on the reduction of chemotherapy-induced leukocytopenia. PATIENTS AND METHODS: Patients of age 61-80 years with aggressive lymphoma were randomly assigned to receive 6 mg pegfilgrastim on day 2 or 4 of a 2-week chemotherapy regimen (R-CHOP-14). RESULTS: Two hundred and ninety-two and 313 chemotherapy cycles were evaluable in 103 patients. Post-nadir pegfilgrastim serum levels were higher after day 4 than after day 2 application. This was associated with an attenuated leukocyte nadir after day 4 pegfilgrastim and there were fewer days with leukocytes <2 × 10(3)/mm(3) compared with day 2 pegfilgrastim. Grade 3 and 4 leukocytopenias (70% versus 43.3%; P < 0.001) and grade 4-only leukocytopenias (47% versus 20.5%; P < 0.001) were more frequent after day 2 pegfilgrastim. There were more chemotherapy cycles with grade 3 and 4 infections after day 2 than day 4 pegfilgrastim (9.4% versus 6.0%; P = 0.118). Interventional antibiotics were given more often after day 2 than after day 4 pegfilgrastim (30.7% versus 21.9% of cycles; P = 0.008). There were five deaths during leukocytopenia after day 2 and none after day 4 pegfilgrastim (P = 0.027). CONCLUSIONS: Administration of pegfilgrastim on day 4 was more effective in reducing severe leukocytopenias and resulted in fewer deaths during leukocytopenia. Pegfilgrastim should be given on day 4 to better exploit its myeloprotective potential.

Isothermal decomposition of hydrogen peroxide dihydrate.

We present a new method of growing pure solid hydrogen peroxide in an ultra high vacuum environment and apply it to determine thermal stability of the dihydrate compound that forms when water and hydrogen peroxide are mixed at low temperatures. Using infrared spectroscopy and thermogravimetric analysis, we quantified the isothermal decomposition of the metastable dihydrate at 151.6 K. This decomposition occurs by fractional distillation through the preferential sublimation of water, which leads to the formation of pure hydrogen peroxide. The results imply that in an astronomical environment where condensed mixtures of H(2)O(2) and H(2)O are shielded from radiolytic decomposition and warmed to temperatures where sublimation is significant, highly concentrated or even pure hydrogen peroxide may form.

Photolysis of pure solid O3 and O2 films at 193 nm.

We studied quantitatively the photochemistry of solid O(3) and O(2) films at 193 nm and 22 K with infrared spectroscopy and microgravimetry. Photolysis of pure ozone destroyed O(3), but a small amount of ozone remained in the film at high fluence. Photolysis of pure O(2) produced O(3) in an amount that increased with photon fluence to a stationary level. For both O(2) and O(3) films, the O(3):O(2) ratio at large fluences is ∼0.07, about two orders of magnitude larger than those obtained in gas phase photolysis. This enhancement is attributed to the increased photodissociation of O(2) due to photoabsorption by O(2) dimers, a process significant at solid-state densities. We obtain initial quantum yield for ozone synthesis from solid oxygen, Φ(O(3)) = 0.24 ± 0.06, and quantum yields for destruction of O(3) and O(2) in their parent solids, Φ(-O(3)) = 1.0 ± 0.2 and Φ(-O(2)) = 0.36 ± 0.1. Combined with known photoabsorption cross sections, we estimate probabilities for geminate recombination of 0.5 ± 0.1 for O(3) fragments and 0.88 ± 0.03 for oxygen atoms from O(2) dissociation. Using a single parameter kinetic model, we deduce the ratio of reaction cross sections for an O atom with O(2) vs. O(3) to be 0.1-0.2. The general good agreement of the model with the data suggests the validity of the central assumption of efficient energy and spin relaxation of photofragments in the solid prior to their reactions with other species.