Patients' experiences of a suppoRted self-manAGeMent pAThway In breast Cancer (PRAGMATIC): quality of life and service use results.

PURPOSE: To describe trends and explore factors associated with quality of life (QoL) and psychological morbidity and assess breast cancer (BC) health service use over a 12-month period for patients joining the supported self-management (SSM)/patient-initiated follow-up (PIFU) pathway. METHODS: Participants completed questionnaires at baseline, 3, 6, 9 and 12 months that measured QoL (FACT-B, EQ 5D-5L), self-efficacy (GSE), psychological morbidity (GHQ-12), roles and responsibilities (PRRS) and service use (cost diary). RESULTS: 99/110 patients completed all timepoints; 32% (35/110) had received chemotherapy. The chemotherapy group had poorer QoL; FACT-B total score mean differences were 8.53 (95% CI: 3.42 to 13.64), 5.38 (95% CI: 0.17 to 10.58) and 8.00 (95% CI: 2.76 to 13.24) at 6, 9 and 12 months, respectively. The odds of psychological morbidity (GHQ12 >4) were 5.5-fold greater for those treated with chemotherapy. Financial and caring burdens (PRRS) were worse for this group (mean difference in change at 9 months 3.25 (95% CI: 0.42 to 6.07)). GSE and GHQ-12 scores impacted FACT-B total scores, indicating QoL decline for those with high baseline psychological morbidity. Chemotherapy patients or those with high psychological morbidity or were unable to carry out normal activities had the highest service costs. Over the 12 months, 68.2% participants phoned/emailed breast care nurses, and 53.3% visited a hospital breast clinician. CONCLUSION: The data suggest that chemotherapy patients and/or those with heightened psychological morbidity might benefit from closer monitoring and/or supportive interventions whilst on the SSM/PIFU pathway. Reduced access due to COVID-19 could have affected service use.

The role of patient-reported outcome measures in trials of artificial intelligence health technologies: a systematic evaluation of ClinicalTrials.gov records (1997-2022).

The extent to which patient-reported outcome measures (PROMs) are used in clinical trials for artificial intelligence (AI) technologies is unknown. In this systematic evaluation, we aim to establish how PROMs are being used to assess AI health technologies. We searched ClinicalTrials.gov for interventional trials registered from inception to Sept 20, 2022, and included trials that tested an AI health technology. We excluded observational studies, patient registries, and expanded access reports. We extracted data regarding the form, function, and intended use population of the AI health technology, in addition to the PROMs used and whether PROMs were incorporated as an input or output in the AI model. The search identified 2958 trials, of which 627 were included in the analysis. 152 (24%) of the included trials used one or more PROM, visual analogue scale, patient-reported experience measure, or usability measure as a trial endpoint. The type of AI health technologies used by these trials included AI-enabled smart devices, clinical decision support systems, and chatbots. The number of clinical trials of AI health technologies registered on ClinicalTrials.gov and the proportion of trials that used PROMs increased from registry inception to 2022. The most common clinical areas AI health technologies were designed for were digestive system health for non-PROM trials and musculoskeletal health (followed by mental and behavioural health) for PROM trials, with PROMs commonly used in clinical areas for which assessment of health-related quality of life and symptom burden is particularly important. Additionally, AI-enabled smart devices were the most common applications tested in trials that used at least one PROM. 24 trials tested AI models that captured PROM data as an input for the AI model. PROM use in clinical trials of AI health technologies falls behind PROM use in all clinical trials. Trial records having inadequate detail regarding the PROMs used or the type of AI health technology tested was a limitation of this systematic evaluation and might have contributed to inaccuracies in the data synthesised. Overall, the use of PROMs in the function and assessment of AI health technologies is not only possible, but is a powerful way of showing that, even in the most technologically advanced health-care systems, patients' perspectives remain central.

Cortical-like colour-encoding neurons in the mushroom body of a butterfly.

Colour is an important visual modality for many animals including insects. The flower-foraging swallowtail butterfly Papilio xuthus has spectrally acute chromatic vision using UV-, blue-, green- and red-sensitive photoreceptors1. The spectral organization of Papilio's retina is well understood but, as for other insects, how chromatic information is processed in higher order brain regions remains unclear. To identify neurons underlying color perception in Papilio, we have investigated the spectral properties of the visual inputs to the mushroom body (MB), a brain region implicated in learning and memory. By recording intracellular responses to a series of monochromatic lights, combined with dye injection, we have revealed a wide variety of spectral responses in three morphologically distinct neuron types. These heterogeneous responses are characterized by colour opponency and sharp tuning to particular wavelengths, which do not in general align with the sensitivities of the retinal photoreceptors, and presumably contribute to Papilio's acute wavelength discrimination. This finding provides new insights into the processing underlying insect colour vision.

Swallowtail Butterflies Use Multiple Visual Cues to Select Oviposition Sites.

Flower-foraging Japanese yellow swallowtail butterflies, Papilio xuthus, exhibit sophisticated visual abilities. When ovipositing, females presumably attempt to select suitable leaves to support the growth of their larval offspring. We first established that butterflies indeed select particular leaves on which to lay eggs; when presented with a single Citrus tree, butterflies significantly favored two out of 102 leaves for oviposition. These preferences were observed across many individuals, implying that they were not merely idiosyncratic, but rather based on properties of the leaves in question. Because the butterflies descended towards the leaves rather directly from a distance, we hypothesized that they base their selection on visual cues. We measured five morphological properties (height, orientation, flatness, roundness, and size) and four reflective features (green reflectance, brightness, and degree and angle of linear polarization). We found that the number of eggs laid upon a leaf was positively correlated with its height, flatness, green reflectance, and brightness, and negatively correlated with its degree of polarization, indicating that these features may serve as cues for leaf selection. Considering that other studies report ovipositing butterflies' preference for green color and horizontally polarized light, butterflies likely use multiple visual features to select egg-laying sites on the host plant.

Treatment Preferences for Cardiac Procedures of Patients With Chronic Kidney Disease in Acute Coronary Syndrome: Design and Pilot Testing of a Discrete Choice Experiment.

BACKGROUND: Chronic kidney disease is associated with a high incidence of acute coronary syndrome and related morbidity and mortality. Treatment choices for patients with chronic kidney disease involve trade-offs in the potential benefits and harms of invasive management options. OBJECTIVE: The objective was to quantify preferences of patients with chronic kidney disease toward invasive heart procedures. DESIGN: Design and pilot a discrete choice experiment. SETTING: We piloted the discrete choice experiment in 2 multidisciplinary chronic kidney disease clinics in Calgary, Alberta, using an 8-question survey. PATIENTS: Eligible patients included those aged 18 years and older, an estimated glomerular filtration rate < 45 mL/min/1.73 m2, not currently receiving dialysis, and able to communicate in English. MEASUREMENTS: Quantification of the average importances of key attributes of invasive heart procedures. METHODS: We identified attributes most important to patients and physicians concerning invasive versus conservative management for acute coronary syndrome, using semi-structured qualitative interviews. Levels for each attribute were derived from analysis of early invasive versus conservative acute coronary syndrome management clinical trials and cohort studies, where subgroups of patients with chronic kidney disease were reported. We designed the pilot study with patient partners with relevant lived experience and considered statistical efficiency to estimate main effects and interactions, as well as response efficiency. Hierarchical Bayesian estimation was used to quantify average importances of attributes. RESULTS: We recruited 43 patients with chronic kidney disease, mean (SD) age 67 (14) years, 67% male, and 35% with a history of cardiovascular disease, of whom 39 completed the survey within 2 weeks of enrollment. The results of the pilot revealed acute kidney injury requiring dialysis and permanent kidney replacement therapy, as well as death within 1 year were the most important attributes. Measures of internal validity for the pilot discrete choice experiment were comparable to those for other published discrete choice experiments. LIMITATIONS: Discrete choice experiments are complex instruments and often cognitively demanding for patients. This survey included multiple risk attributes which may have been challenging for some patients to understand. CONCLUSIONS: This pilot study demonstrates the feasibility of a discrete choice experiment to quantify preferences of patients with chronic kidney disease toward the benefits and trade-offs related to invasive versus conservative management for acute coronary syndrome. These preliminary findings suggest that patients with chronic kidney disease may be on average similarly risk averse toward kidney replacement therapy and death. This pilot information will be used to inform a larger discrete choice experiment that will refine these estimates of patient preferences and characterize subgroups with distinct treatment preferences, which should provide new knowledge that can facilitate shared decision-making between patients with chronic kidney disease and their care providers in the setting of acute coronary syndrome.

CONTEXTE: L'insuffisance rénale chronique (IRC) est associée à une forte incidence du syndrome coronarien aigu, de même qu'à la morbidité et à la mortalité qui y sont liées. Les options de traitement pour les patients atteints d'IRC impliquent de faire des compromis sur les avantages et inconvénients des options invasives. OBJECTIF: Quantifier les préférences des patients atteints d'IRC quant aux procédures cardiaques invasives. CONCEPTION: Concevoir et piloter une expérience avec choix discrets. CADRE: Nous avons mené cette expérience avec choix discrets dans deux cliniques multidisciplinaires de néphropathie chronique de Calgary (Alberta) à l'aide d'un sondage en huit questions. SUJETS: Les patients admissibles étaient des adultes avec un débit de filtration glomérulaire estimé (DFGe) inférieur à 45 mL/min/1,73 m 2 et ne suivant pas de traitements de dialyse. Les patients inclus devaient être capables de communiquer en anglais. MESURES: Quantification de l'importance moyenne des principaux attributs des procédures cardiaques effractives. MÉTHODOLOGIE: Les attributs les plus importants pour les patients et les médecins concernant une gestion invasive par rapport à une gestion conservatrice du syndrome coronarien aigu ont été déterminés à l'aide d'interviews qualitatives semi-structurées. L'analyse d'essais cliniques et d'études de cohorte ayant inclus des sous-groupes de patients atteints d'IRC et portant sur la gestion invasive précoce du syndrome coronarien aigu par opposition à une gestion conservatrice a permis de dériver les le degré d'importance pour chaque attribut. Nous avons conçu l'étude pilote en compagnie de patients partenaires ayant une expérience vécue pertinente et nous avons tenu compte de l'efficacité statistique pour estimer les principaux effets et interactions, de même que l'efficacité de la réponse. Une estimation hiérarchique bayésienne a été employée pour quantifier l'importance moyenne des attributs. RÉSULTATS: Nous avons recruté 43 patients atteints d'IRC dont l'âge moyen (É-T) était de 67 ans (14). La cohorte était constituée à 67 % d'hommes et 35 % des sujets avaient des antécédents de maladies cardiovasculaires. L'étude porte sur les 39 patients ayant rempli le questionnaire dans les deux semaines suivant le recrutement. Les résultats de l'étude pilote ont révélé que la mortalité dans la première année et l'insuffisance rénale aiguë (IRA) nécessitant la dialyse et une thérapie de remplacement rénal permanente étaient les attributs les plus importants. Les mesures des intervalles de validité de cette expérience pilote avec choix discrets étaient similaires à ceux des autres expériences publiées du même type. LIMITES: Les expériences avec choix discrets sont des outils complexes et souvent exigeants pour les patients sur le plan cognitif. Ce questionnaire comportait plusieurs attributs de risque qui ont peut-être été difficiles à comprendre pour certains patients. CONCLUSION: Cette étude pilote démontre la faisabilité d'une expérience avec choix discrets pour qualifier les préférences des patients atteints d'IRC en ce qui concerne les avantages et les compromis liés à une gestion invasive ou conservatrice du syndrome coronarien aigu. Ces résultats préliminaires semblent indiquer que les patients atteints d'IRC seraient en moyenne tout aussi réticents envers le risque de thérapie de remplacement rénal qu'envers le risque de décès. Les informations tirées de ce pilote serviront à orienter une plus vaste expérience avec choix discrets qui raffinera ces estimations des préférences des patients et caractérisera les sous-groupes ayant des préférences de traitements distinctes. Ceci fournira de nouvelles connaissances susceptibles de faciliter la prise de décision partagée entre les patients atteints d'IRC et leurs fournisseurs de soins dans le contexte du syndrome coronarien aigu.

Retinal organization and visual abilities for flower foraging in swallowtail butterflies.

Papilio butterflies' ability to forage for flowers relies upon multiple visual cues such as color, brightness, and motion. Papilio learns the color of rewarding flowers and detects it at a distance. Its color vision is based on four photoreceptor classes: UV, blue, green, and red, providing sensitive wavelength discrimination. These four receptor classes also contribute to the perception of brightness and polarization. Papilio's motion vision is based on a different set of receptors: green, red, and broad band. This implies that two visual pathways exist in Papilio. The contribution of several receptor classes not only for chromatic vision but also achromatic vision likely enhances the butterfly's ability to detect flowers in complex visual environments.

CNS germinoma with extensive calcification: An unusual histologic finding.

INTRODUCTION: Intratumoral calcification is a feature that is more often observed in pineal parenchymal tumour than germinoma. We describe a 13-year-old male with pineal region germinoma demonstrating extensive intratumoral calcification. CASE REPORT: He presented with worsening headache that was associated with fatigue, nausea and vomiting. Radiologic examination revealed a multilobular mass in the pineal region with internal calcifications. Biopsy showed a pure germinoma with unusually extensive calcification. DISCUSSION: Although a diagnosis may be suggested with a careful evaluation of imaging, there is no pathognomonic pattern. Thus, histologic verification is necessary for most pineal region masses.

Monopolatic motion vision in the butterfly Papilio xuthus.

The swallowtail butterfly Papilio xuthus can perceive the linear polarization of light. Using a novel polarization projection system, we recently demonstrated that P. xuthus can detect visual motion based on polarization contrast. In the present study, we attempt to infer via behavioural experiments the mechanism underlying this polarization-based motion vision. Papilio xuthus do not perceive contrast between unpolarized and diagonally polarized light, implying that they cannot unambiguously estimate angle and degree of polarization, at least as far as motion detection is concerned. Furthermore, they conflate brightness and polarization cues, such that bright vertically polarized light resembles dim unpolarized light. These observations are consistent with a one-channel 'monopolatic' detector mechanism. We extend our existing model of motion vision in P. xuthus to incorporate these polarization findings, and conclude that the photoreceptors likely to form the basis for the putative monopolatic polarization detector are R3 and R4, which respond maximally to horizontally polarized green light. R5-R8, we propose, form a polarization-insensitive secondary channel tuned to longer wavelengths of light. Consistent with this account, we see greater sensitivity to polarization for green-light stimuli than for subjectively equiluminant red ones. Somewhat counter-intuitively, our model predicts greatest sensitivity to vertically polarized light; owing to the non-linearity of photoreceptor responses, light polarized to an angle orthogonal to a monopolatic detector's orientation offers the greatest contrast with unpolarized light.

The Dominant Role of Visual Motion Cues in Bumblebee Flight Control Revealed Through Virtual Reality.

Flying bees make extensive use of optic flow: the apparent motion in the visual scene generated by their own movement. Much of what is known about bees' visually-guided flight comes from experiments employing real physical objects, which constrains the types of cues that can be presented. Here we implement a virtual reality system allowing us to create the visual illusion of objects in 3D space. We trained bumblebees, Bombus ignitus, to feed from a static target displayed on the floor of a flight arena, and then observed their responses to various interposing virtual objects. When a virtual floor was presented above the physical floor, bees were reluctant to descend through it, indicating that they perceived the virtual floor as a real surface. To reach a target at ground level, they flew through a hole in a virtual surface above the ground, and around an elevated virtual platform, despite receiving no reward for avoiding the virtual obstacles. These behaviors persisted even when the target was made (unrealistically) visible through the obstructing object. Finally, we challenged the bees with physically impossible ambiguous stimuli, which give conflicting motion and occlusion cues. In such cases, they behaved in accordance with the motion information, seemingly ignoring occlusion.

Young adult pregnancy status and the risk of developing overweight and obesity among women and men.

Pregnancies can end in miscarriage, birth or termination. Although it is well known that pregnancy results in weight gain across the life course, it is unknown whether pregnancies which end in termination and miscarriage contribute to this. The study used a sub-sample of 3630 adult offspring from the original cohort of the Mater University of Queensland Study of Pregnancy (MUSP) and its outcomes, in Brisbane, Australia. Anthropometric data were measured at 5, 14 and 21 years of age and experience of pregnancy including termination, miscarriage and births were self-reported at 21 years. Multivariable analyses were conducted to determine whether pregnancy status of young people independently associated with overweight or obesity status. The women who had at least one birth were more likely to have overweight (odds ratio [OR] 1.52; 95% confidence interval [CI]: 1.01, 2.27) or obese (OR 2.38; 95% CI: 1.58, 3.59) compared to women who did not experience any pregnancy. Women whose pregnancies were terminated or miscarried were at the same risk of overweight or obesity as women who did not experience any pregnancy. For men, there is no association between the pregnancies in their partners and the mean difference in their body mass index. Young women whose pregnancies result in a birth, but not terminations or miscarriages, are at greater risk of having overweight or obesity following the birth.

A Novel Display System Reveals Anisotropic Polarization Perception in the Motion Vision of the Butterfly Papilio xuthus.

While the linear polarization of light is virtually invisible to humans, many invertebrates' eyes can detect it. How this information is processed in the nervous system, and what behavioral function it serves, are in many cases unclear. One reason for this is the technical difficulty involved in presenting images or video containing polarization contrast, particularly if intensity and/or color contrast is also required. In this primarily methods-focused article, we present a novel technique based on projecting video through a synchronously rotating linear polarizer. This approach allows the intensity, angle of polarization, degree of linear polarization, and potentially also color of individual pixels to be controlled independently. We characterize the performance of our system, and then use it to investigate the relationship between polarization and motion vision in the swallowtail butterfly Papilio xuthus. Although this animal has photoreceptors sensitive to four different polarization angles, we find that its motion vision cannot distinguish between diagonally-polarized and unpolarized light. Furthermore, it responds more strongly to vertically-polarized moving objects than horizontally-polarized ones. This implies that Papilio's polarization-based motion detection employs either an unbalanced two-channel (dipolatic) opponent architecture, or possibly a single-channel (monopolatic) scheme without opponent mechanisms.

Red-shift of spectral sensitivity due to screening pigment migration in the eyes of a moth, Adoxophyes orana.

BACKGROUND: We have found that the spectral sensitivity of the compound eye in the summer fruit tortrix moth (Adoxophyes orana) differs in laboratory strains originating from different regions of Japan. We have investigated the mechanisms underlying this anomalous spectral sensitivity. METHODS: We applied electrophysiology, light and electron microscopy, opsin gene cloning, mathematical modeling, and behavioral analysis. RESULTS: The ERG-determined spectral sensitivity of dark-adapted individuals of all strains peaks around 520 nm. When light-adapted, the spectral sensitivity of the Nagano strain narrows and its peak shifts to 580 nm, while that in other strains remains unchanged. All tested strains appear to be identical in terms of the basic structure of the eye, the pigment migration in response to light- and dark-adaptation, and the molecular structure of long-wavelength absorbing visual pigments. However, the color of the perirhabdomal pigment clearly differs; it is orange in the Nagano strain and purple in the others. The action spectrum of phototaxis appears to be shifted towards longer wavelengths in the Nagano individuals. CONCLUSIONS: The spectral sensitivities of light-adapted eyes can be modeled under the assumption that this screening pigment plays a crucial role in determining the spectral sensitivity. The action spectrum of phototaxis indicates that the change in the eye spectral sensitivity is behaviorally relevant.

Marrow-ablative chemotherapy followed by tandem autologous hematopoietic cell transplantation in pediatric patients with malignant brain tumors.

To improve survival in young children with malignant brain tumors, irradiation-avoiding or -minimizing marrow-ablative chemotherapy (HDCx) with autologous hematopoietic cell transplantation (AuHCT) has been investigated. We evaluated the outcome of 44 children with malignant brain tumors treated with HDCx and tandem AuHCT at Children's Hospital Los Angeles between June 1999 and July 2012. Forty-four children with malignant brain tumors were studied. Twenty-one had medulloblastoma/primitive neuro-ectodermal tumor, eight atypical teratoid/rhabdoid tumor (ATRT), five high-grade glioma, four malignant germ cell tumor, three ependymoma and three choroid plexus carcinoma. Twenty-nine patients received three tandem transplants and 15 received two tandem transplants, respectively. The 5-year PFS and overall survivals (OS) for all patients were 46.3±8.2% and 51.7±8.5%, respectively. The PFS and OS for 27 newly diagnosed patients were 68.9±9.9% and 73.5±9.3%, respectively, compared with 17 transplanted at relapse 11.8±9.8% (P<0.001) and 15.1±12.3% (P=0.0231), respectively. The 5-year PFS and OS in 13 previously unirradiated patients were 74±13% and 74±13% versus 33.2±9.8% and 40.2±10.6% in 31 irradiated patients (P=0.11 and P=0.239), respectively. One patient died of transplant-related toxicity. HDCx with tandem AuHCT is feasible and safe in children with malignant brain tumors with encouraging irradiation-free survival in newly diagnosed children.

Multisensory integration in Lepidoptera: Insights into flower-visitor interactions.

As most work on flower foraging focuses on bees, studying Lepidoptera can offer fresh perspectives on how sensory capabilities shape the interaction between flowers and insects. Through a combination of innate preferences and learning, many Lepidoptera persistently visit particular flower species. Butterflies tend to rely on their highly developed sense of colour to locate rewarding flowers, while moths have evolved sophisticated olfactory systems towards the same end. However, these modalities can interact in complex ways; for instance, butterflies' colour preference can shift depending on olfactory context. The mechanisms by which such cross-modal interaction occurs are poorly understood, but the mushroom bodies appear to play a central role. Because of the diversity seen within Lepidoptera in terms of their sensory capabilities and the nature of their relationships with flowers, they represent a fruitful avenue for comparative studies to shed light on the co-evolution of flowers and flower-visiting insects.

Evaluation of the risks of chemotherapy in dogs with thrombocytopenia.

Thrombocytopenia is commonly encountered in veterinary oncology. Currently, there are no standard guidelines regarding the administration of chemotherapy to the patients with thrombocytopenia. This observational epidemiological cohort study aimed to determine whether thrombocytopenic dogs were at increased risk of gastrointestinal adverse effects (vomiting, diarrhoea, inappetence) or haemorrhage following administration of standard doses of chemotherapy. The adverse effects following 77 prospectively identified episodes of thrombocytopenia (platelet count, <200 000 µL-1 ) were compared with the adverse effects experienced in a retrospective cohort (platelet count >200 000 µL-1 ), and evaluated by statistical analysis. Overall, there was no statistically significant difference in the incidence of gastrointestinal adverse effects or haemorrhage between thrombocytopenic and control dogs. The control group of dogs with lymphoma were statistically more likely to experience vomiting as an adverse effect of chemotherapy (P = 0.028). The results presented here showed no evidence for an increased risk of gastrointestinal adverse effects or haemorrhage in thrombocytopenic dogs after receiving standard doses of chemotherapy.

Winter diet of brown trout Salmo trutta in groundwater-dominated streams: influence of environmental factors on spatial and temporal variation.

Winter diet composition of brown trout Salmo trutta was quantified from November to March in 35 temperate groundwater-dominated streams in south-eastern Minnesota, U.S.A., in relation to stream physical characteristics including drainage area, channel slope and influence of groundwater on stream thermal regime. Aquatic invertebrates made up the majority of S. trutta diet in all streams and sampling periods and individual S. trutta typically had consumed 30 or more prey items at each sampling event. Differences in diet composition were greater among streams than between sampling periods within a stream, with Gammarus spp., Brachycentrus spp., Glossosoma spp., Chironomidae and Physella spp. the most common taxa. Landscape-scale stream characteristics were not significantly associated with S. trutta consumption or diet composition. Winter was period of significant activity in groundwater-dominated streams, as S. trutta fed on a variety of aquatic prey taxa highlighting the importance of winter base-flow in moderating S. trutta populations in seasonally cold catchments.

Attachment of Algal Cells to Zwitterionic Self-Assembled Monolayers Comprised of Different Anionic Compounds.

The influence of zwitterionic self-assembled monolayers on settlement and removal of algae was studied. The monolayers were constructed either from zwitterionic thiols or from solutions of positively and negatively charged thiols. The cationic component was composed of quaternary ammonium terminated thiols and the anionic component contained sulfate or carboxylate termination. During assembly, all surfaces showed a strong tendency for equilibration of the surface charge. Settlement and adhesion assays with zoospores of Ulva linza and the diatom Navicula incerta, and field tests of the initial surface colonization revealed the relevance of charge equilibration for the biological inertness of the prepared surfaces.

Decreased morbidity and mortality of autologous hematopoietic transplants for children with malignant central nervous system tumors: the 'Head Start' trials, 1991-2009.

Since 1991, three sequential prospective clinical trials have been conducted by the 'Head Start' (HS) Consortium in which young children with newly-diagnosed malignant central nervous system (CNS) tumors were treated with induction chemotherapy followed by single-cycle marrow-ablative chemotherapy and autologous hematopoietic rescue as a means of improving disease cure rate and quality of survival through avoidance (<6 years old at diagnosis) or reduction (6-10 years old) of brain irradiation. Bone Marrow (HS I) or filgrastim-mobilized peripheral hematopoietic cells (HS II and III) were obtained following recovery from the first and/or second induction cycles. Radiotherapy was administered following all chemotherapy only for patients with residual tumor following completion of induction or with age greater than 6 years at diagnosis. Two hundred and twenty-six children were enrolled on three consecutive HS trials with primary malignant CNS tumors and underwent marrow-ablative chemotherapy. The 100-day treatment-related mortality (TRM) steadily declined as did grade IV transplant-related oropharyngeal mucositis. Factors most likely associated with the decrease in TRM and morbidity are increasing experience with the marrow-ablative chemotherapy regimen combined with improved leukapheresis and post-reinfusion supportive care techniques, contributing toward improved overall survival.

Phase I study of temozolomide in combination with thiotepa and carboplatin with autologous hematopoietic cell rescue in patients with malignant brain tumors with minimal residual disease.

Recurrence of malignant brain tumors results in a poor prognosis with limited treatment options. High-dose chemotherapy with autologous hematopoietic cell rescue (AHCR) has been used in patients with recurrent malignant brain tumors and has shown improved outcomes compared with standard chemotherapy. Temozolomide is standard therapy for glioblastoma and has also shown activity in patients with medulloblastoma/primitive neuro-ectodermal tumor (PNET), particularly those with recurrent disease. Temozolomide was administered twice daily on days -10 to -6, followed by thiotepa 300 mg/m(2) per day and carboplatin dosed using the Calvert formula or body surface area on days -5 to -3, with AHCR day 0. Twenty-seven patients aged 3-46 years were enrolled. Diagnoses included high-grade glioma (n=12); medulloblastoma/PNET (n=9); central nervous system (CNS) germ cell tumor (n=4); ependymoma (n=1) and spinal cord PNET (n=1). Temozolomide doses ranged from 100 mg/m(2) per day to 400 mg/m(2) per day. There were no toxic deaths. Prolonged survival was noted in several patients including those with recurrent high-grade glioma, medulloblastoma and CNS germ cell tumor. Increased doses of temozolomide are feasible with AHCR. A phase II study using temozolomide, carboplatin and thiotepa with AHCR for children with recurrent malignant brain tumors is being conducted through the Pediatric Blood and Marrow Transplant Consortium.

Resistance of Amphiphilic Polysaccharides against Marine Fouling Organisms.

Amphiphilic coatings are promising candidates for fouling-release applications. As hydrophilic components, polysaccharides are interesting and environmentally benign building blocks. We used covalently coupled alginic acid (AA) and hyaluronic acid (HA) and postmodified them with a hydrophobic fluorinated amine. The surfaces showed good stability under marine conditions and fluorination led to a decreased uptake of Ca(2+) ions after modification. In single species settlement assays (bacteria, diatoms, barnacle cypris larvae), the modification decreased the settlement density and/or the adhesion strength of many of the tested species. Field studies supported findings of the laboratory experiments, as hydrophobic modification of AA and HA decreased diatom colonization.