Impact of the COVID-19 Pandemic on Outcomes for Patients with Lung Cancer Receiving Curative-intent Radiotherapy in the UK.

AIMS: Previous work found that during the first wave of the COVID-19 pandemic, 34% of patients with lung cancer treated with curative-intent radiotherapy in the UK had a change to their centre's usual standard of care treatment (Banfill et al. Clin Oncol 2022;34:19-27). We present the impact of these changes on patient outcomes. MATERIALS AND METHODS: The COVID-RT Lung database was a prospective multicentre UK cohort study including patients with stage I-III lung cancer referred for and/or treated with radical radiotherapy between April and October 2020. Data were collected on patient demographics, radiotherapy and systemic treatments, toxicity, relapse and death. Multivariable Cox and logistic regression were used to assess the impact of having a change to radiotherapy on survival, distant relapse and grade ≥3 acute toxicity. The impact of omitting chemotherapy on survival and relapse was assessed using multivariable Cox regression. RESULTS: Patient and follow-up forms were available for 1280 patients. Seven hundred and sixty-five (59.8%) patients were aged over 70 years and 603 (47.1%) were female. The median follow-up was 213 days (119, 376). Patients with stage I-II non-small cell lung cancer (NSCLC) who had a change to their radiotherapy had no significant increase in distant relapse (P = 0.859) or death (P = 0.884); however, they did have increased odds of grade ≥3 acute toxicity (P = 0.0348). Patients with stage III NSCLC who had a change to their radiotherapy had no significant increase in distant relapse (P = 0.216) or death (P = 0.789); however, they did have increased odds of grade ≥3 acute toxicity (P < 0.001). Patients with stage III NSCLC who had their chemotherapy omitted had no significant increase in distant relapse (P = 0.0827) or death (P = 0.0661). CONCLUSION: This study suggests that changes to radiotherapy and chemotherapy made in response to the COVID-19 pandemic did not significantly affect distant relapse or survival. Changes to radiotherapy, namely increased hypofractionation, led to increased odds of grade ≥3 acute toxicity. These results are important, as hypofractionated treatments can help to reduce hospital attendances in the context of potential future emergency situations.

Searching for better X-ray and γ-ray photodetectors: structure-composition properties of the TlPb2Br5-x I x quaternary system.

Developing X-ray and γ-ray detectors with stable operation at ambient temperature and high energy resolution is an open challenge. Here, we present an approach to search for new detector materials, combining binary photodetector compounds. More specifically, we explore quaternary TlPb2Br5-x I x compositions, relying on materials synergy between TlBr, TlI, and PbI2 photodetectors. We discover a broad solid solution in the TlPb2Br5-'TlPb2I5' section, which can be derived from a new quaternary compound, TlPb2BrI4, by partial substitution of Br by I atoms on the 4c site or by replacement of I by Br atoms on the 16l site. We carry out a thorough crystallographic analysis of the new TlPb2BrI4 compound and prepare a high-quality standardized structure file. We also complete the phase diagram of the TlPb2Br5-'TlPb2I5' section, based on 21 alloys. Furthermore, we synthesize a series of high quality centimeter-sized TlPb2Br5-x I x single crystals (x = 2, 2.5, 3, 3.5, 4, 4.5) by the Bridgman-Stockbarger method and study their structure and properties using a combination of experimental techniques (X-ray diffraction, X-ray photoelectron spectroscopy, and absorption spectroscopy) and theoretical calculations.

Changes in the Management of Patients having Radical Radiotherapy for Lung Cancer during the First Wave of the COVID-19 Pandemic in the UK.

AIMS: In response to the COVID-19 pandemic, guidelines on reduced fractionation for patients treated with curative-intent radiotherapy were published, aimed at reducing the number of hospital attendances and potential exposure of vulnerable patients to minimise the risk of COVID-19 infection. We describe the changes that took place in the management of patients with stage I-III lung cancer from April to October 2020. MATERIALS AND METHODS: Lung Radiotherapy during the COVID-19 Pandemic (COVID-RT Lung) is a prospective multicentre UK cohort study. The inclusion criteria were: patients with stage I-III lung cancer referred for and/or treated with radical radiotherapy between 2nd April and 2nd October 2020. Patients who had had a change in their management and those who continued with standard management were included. Data on demographics, COVID-19 diagnosis, diagnostic work-up, radiotherapy and systemic treatment were collected and reported as counts and percentages. Patient characteristics associated with a change in treatment were analysed using multivariable binary logistic regression. RESULTS: In total, 1553 patients were included (median age 72 years, 49% female); 93 (12%) had a change to their diagnostic investigation and 528 (34%) had a change to their treatment from their centre's standard of care as a result of the COVID-19 pandemic. Age ≥70 years, male gender and stage III disease were associated with a change in treatment on multivariable analysis. Patients who had their treatment changed had a median of 15 fractions of radiotherapy compared with a median of 20 fractions in those who did not have their treatment changed. Low rates of COVID-19 infection were seen during or after radiotherapy, with only 21 patients (1.4%) developing the disease. CONCLUSIONS: The COVID-19 pandemic resulted in changes to patient treatment in line with national recommendations. The main change was an increase in hypofractionation. Further work is ongoing to analyse the impact of these changes on patient outcomes.

Reference Protocol to Assess Analytical Performance of Higher Order Structural Analysis Measurements: Results from an Interlaboratory Comparison.

Measurements of protein higher order structure (HOS) provide important information on stability, potency, efficacy, immunogenicity, and biosimilarity of biopharmaceuticals, with a significant number of techniques and methods available to perform these measurements. The comparison of the analytical performance of HOS methods and the standardization of the results is, however, not a trivial task, due to the lack of reference protocols and reference measurement procedures. Here, we developed a protocol to structurally alter and compare samples of somatropin, a recombinant biotherapeutic, and describe the results obtained by using a number of techniques, methods and in different laboratories. This, with the final aim to provide tools and generate a pool of data to compare and benchmark analytical platforms and define method sensitivity to structural changes. Changes in somatropin HOS, induced by the presence of zinc at increasing concentrations, were observed, both globally and at more localized resolution, across many of the methods utilized in this study and with different sensitivities, suggesting the suitability of the protocol to improve understanding of inter- and cross-platform measurement comparability and assess analytical performance as appropriate.

[Face protective patches do not reduce facial pressure ulcers in a simulated model of non-invasive ventilation]. / Uso de parches protectores faciales no reduce la presión facial en un modelo simulado de ventilación mecánica no invasiva.

Noninvasive ventilation (NIV) frequently involves the development of facial pressure ulcers (FPU). Its prevention considers the empirical use of protective patches between skin and mask, in order to reduce the pressure exerted by it. OBJECTIVES: To evaluate the effect of protective patches on the pressure exerted by the facial mask, and its impact on the programmed ventilatory parameters. METHOD: Bilevel NIV simulated model using full face mask in phantom with a physiological airway (ALS PRO +) in supine position. Forehead, chin and cheekbones pressure were measured using 3 types of standard protective patches versus a control group using pressure sensors (Interlinks Electronics®). The values obtained with the protective patches-mask model were evaluated in the programmed variables maximum inspiratory flow (MIF)), expired tidal volume (Vte) and positive inspiratory pressure (IPAP), with Trilogy 100 ventilator, Respironics®. The programming and recording of the variables was carried out in 8 opportunities in each group by independent operators. RESULTS: There was no decrease in facial pressure with any of the protective patches compared to the control group. Moltopren increased facial pressure at all support points (p < 0.001), increased leakage, it decreased MIF, Vte and IPAP (p < 0.001). Hydrocolloid patches increased facial pressure only in the left cheekbone, increased leakage and decreased MIF. Polyurethane patches did not produce changes in facial pressure or ventilatory variables. CONCLUSION: The use of protective patches of moltopren, hydrocolloid and polyurethane transparent did not contribute to the decrease of the facial pressure. A deleterious effect of the moltopren and hydrocolloid patches was observed on the administration of ventilatory variables, concluding that the non-use of the protective patches allowed a better administration of the programmed parameters.

Uso de parches protectores faciales no reduce la presión facial en un modelo simulado de ventilación mecánica no invasiva / Face protective patches do not reduce facial pressure ulcers in a simulated model of non-invasive ventilation

La ventilación mecánica no invasiva (VMNI) tiene como complicación frecuente el desarrollo de úlceras faciales por presión (UPP). Su prevención considera el uso empírico de parches protectores entre piel y mascarilla, para disminuir la presión ejercida por ésta. Objetivos: Evaluar el efecto de los parches protectores sobre la presión ejercida por la mascarilla facial, y su impacto en los parámetros ventilatorios programados. Método: Modelo simulado de VMNI binivelada usando mascarilla facial total en fantoma con vía aérea fisiológica (ALS PRO+) en posición supina. Se midió la presión en frente, mentón y pómulos, usando 3 tipos de parches protectores de uso habitual versus un grupo control, utilizando sensores de presión (Interlinks Electronics®). Se evaluaron los valores obtenidos con el modelo de mascarilla-parches protectores en las variables programadas flujo máximo inspiratorio (FMI), volumen corriente espirado (Vte) y presión positiva inspiratoria (IPAP), con ventilador Trilogy 100, Respironics®. La programación y registro de las variables fue efectuada en 8 oportunidades en cada grupo por operadores independientes. Resultados: No se observó disminución de la presión facial con ninguno de los parches protectores respecto al grupo control. Moltoprén aumentó la presión facial en todos los puntos de apoyo (p < 0,001), aumentó fuga, disminuyó FMI, Vte e IPAP (p < 0,001). Parches de hidrocoloide aumentaron la presión facial sólo en pómulo izquierdo, aumentaron la fuga y disminuyeron FMI. Parches de poliuretano no generaron cambios en la presión facial ni en variables ventilatorias. Conclusión: El uso de parches protectores de moltoprén, hidrocoloide y poliuretano transparente no contribuyó a la disminución de la presión facial. Se observó un efecto deletéreo de los parches de moltoprén e hidrocoloide sobre la administración de variables ventilatorias, concluyendo que el no uso de los parches protectores permitió una mejor administración de los parámetros programados.

Noninvasive ventilation (NIV) frequently involves the development of facial pressure ulcers (FPU). Its prevention considers the empirical use of protective patches between skin and mask, in order to reduce the pressure exerted by it. Objectives: To evaluate the effect of protective patches on the pressure exerted by the facial mask, and its impact on the programmed ventilatory parameters. Method: Bilevel NIV simulated model using full face mask in phantom with a physiological airway (ALS PRO +) in supine position. Forehead, chin and cheekbones pressure were measured using 3 types of standard protective patches versus a control group using pressure sensors (Interlinks Electronics®). The values obtained with the protective patches-mask model were evaluated in the programmed variables maximum inspiratory flow (MIF)), expired tidal volume (Vte) and positive inspiratory pressure (IPAP), with Trilogy 100 ventilator, Respironics®. The programming and recording of the variables was carried out in 8 opportunities in each group by independent operators. Results: There was no decrease in facial pressure with any of the protective patches compared to the control group. Moltopren increased facial pressure at all support points (p < 0.001), increased leakage, it decreased MIF, Vte and IPAP (p < 0.001). Hydrocolloid patches increased facial pressure only in the left cheekbone, increased leakage and decreased MIF. Polyurethane patches did not produce changes in facial pressure or ventilatory variables. Conclusion: The use of protective patches of moltopren, hydrocolloid and polyurethane transparent did not contribute to the decrease of the facial pressure. A deleterious effect of the moltopren and hydrocolloid patches was observed on the administration of ventilatory variables, concluding that the non-use of the protective patches allowed a better administration of the programmed parameters.

Cherenkov light production from the α-emitting decay chains of 223Ra, 212Pb, and 149Tb for Cherenkov Luminescence Imaging.

Cherenkov Luminescence Imaging (CLI) is a new method to image radioactive therapeutic and diagnostic agents, primarily in preclinical studies. This study used Geant4 and Python to generate the predicted Cherenkov light production as a function of time for a set of isotopic chains of interest for targeted alpha therapy: 223Ra, 212Pb, and 149Tb. All are shown to produce substantial Cherenkov light, though time delays between initial decays and the production of Cherenkov light requires caution in interpreting CLI.

[High flow nasal cannula in infants: Experience in a critical patient unit]. / Cánula nasal de alto flujo en lactantes: experiencia en una unidad de paciente crítico.

INTRODUCTION: The high flow nasal cannula (HFNC) is a method of respiratory support that is increasingly being used in paediatrics due to its results and safety. OBJECTIVE: To determine the efficacy of HFNC, as well as to evaluate the factors related to its failure and complications associated with its use in infants. PATIENTS AND METHOD: An analysis was performed on the demographic, clinical, blood gas, and radiological data, as well as the complications of patients connected to a HFNC in a critical care unit between June 2012 and September 2014. A comparison was made between the patients who failed and those who responded to HFNC. A failure was considered as the need for further respiratory support during the first 48hours of connection. The Kolmogorov Smirnov, Mann-Whitney U, chi squared and the Exact Fisher test were used, as well as correlations and a binary logistic regression model for P≤.05. RESULTS: The study included 109 patients, with a median age and weight: 1 month (0.2-20 months) and 3.7kg (2-10kg); 95 percentile: 3.7 months and 5.7kg, respectively. The most frequent diagnosis and radiological pattern was bronchiolitis (53.2%) and interstitial infiltration (56%). Around 70.6% responded. There was a significant difference between failure and response in the diagnosis (P=.013), radiography (P=018), connection context (P<.0001), pCO2 (median 40.7mmHg [15.4-67 mmHg] versus 47.3mmHg [28.6-71.3mmHg], P=.004) and hours on HFNC (median 60.75hrs [5-621.5 hrs] versus 10.5hrs [1-29 hrs], P<.0001). The OR of the PCO2 ≥ 55mmHg for failure was 2.97 (95% CI; 1.08-8.17; P=.035). No patient died and no complications were recorded. CONCLUSION: The percentage success observed was similar to that published. In this sample, the failure of HFNC was only associated with an initial pCO2 ≥ 55mmHg. On there being no complications reported as regards it use, it is considered safe, although a randomised, controlled, multicentre study is required to compare and contrast these results.

Cánula nasal de alto flujo en lactantes: experiencia en una unidad de paciente crítico / High flow nasal cannula in infants: Experience in a critical patient unit

Introducción: La cánula nasal de alto flujo (CNAF) es un método de soporte respiratorio cada vez más utilizado en pediatría por sus resultados y seguridad. Objetivo: Determinar la efectividad de la CNAF, evaluar factores asociados a fracaso y complicaciones relacionadas con su uso en lactantes. Pacientes y método: Se analizaron los datos demográficos, clínicos, gasométricos, radiológicos y complicaciones de los pacientes conectados a CNAF en una unidad crítica entre junio de 2012 y septiembre de 2014. Se compararon los pacientes que fracasaron con los respondedores a CNAF, considerándose fracaso la necesidad de un mayor soporte respiratorio durante las primeras 48 h de conexión. Se utilizó test de Kolmogorov Smirnov, U de Mann-Whitney, Chi cuadrado, test exacto de Fisher, correlaciones y Modelo de regresión logística binaria para p ≤ 0,05. Resultados: Un total de 109 pacientes. Mediana de edad y peso: 1 mes (0,2-20 meses) y 3,7 kg (2-10 kg); percentil 95: 3,7 meses y 5,7 kg respectivamente. El diagnóstico y patrón radiológico más frecuente fue bronquiolitis (53,2%) e infiltrado intersticial (56%). Un 70,6% respondió. Hubo diferencia significativa entre fracaso y respuesta en el diagnóstico (p = 0,013), radiografía (p = 0,018), contexto de conexión (p < 0,0001), pCO2 (mediana 40,7 mm Hg [15,4-67 mm Hg] versus 47,3 mm Hg [28,6-71,3 mm Hg], p = 0,004) y horas de CNAF (mediana 60,75 h [5-621,5 h] versus 10,5 h [1-29 h], p < 0,0001). El OR de PCO2 ≥ 55 mm Hg para fracaso fue 2,97 (IC 95%: 1,08-8,17; p = 0,035). Ningún paciente falleció ni registró complicaciones. Conclusión: El porcentaje de éxito observado fue similar a lo publicado. En esta muestra el fracaso de CNAF solo se asoció a una pCO2 inicial ≥ 55 mm Hg. Su uso se consideró seguro al no reportarse complicaciones relacionadas a su utilización. Se requiere de un estudio multicéntrico, aleatorizado y controlado para contrastar estos resultados.

Introduction: The high flow nasal cannula (HFNC) is a method of respiratory support that is increasingly being used in paediatrics due to its results and safety. Objective: To determine the efficacy of HFNC, as well as to evaluate the factors related to its failure and complications associated with its use in infants. Patients and method: An analysis was performed on the demographic, clinical, blood gas, and radiological data, as well as the complications of patients connected to a HFNC in a critical care unit between June 2012 and September 2014. A comparison was made between the patients who failed and those who responded to HFNC. A failure was considered as the need for further respiratory support during the first 48 hours of connection. The Kolmogorov Smirnov, Mann-Whitney U, chi squared and the Exact Fisher test were used, as well as correlations and a binary logistic regression model for P ≤ .05. Results: The study included 109 patients, with a median age and weight: 1 month (0.2-20 months) and 3.7 kg (2-10 kg); 95 percentile: 3.7 months and 5.7 kg, respectively. The most frequent diagnosis and radiological pattern was bronchiolitis (53.2%) and interstitial infiltration (56%). Around 70.6% responded. There was a significant difference between failure and response in the diagnosis (P = .013), radiography (P = 018), connection context (P < .0001), pCO2 (median 40.7 mmHg [15.4-67 mmHg] versus 47.3 mmHg [28.6-71.3 mmHg], P = .004) and hours on HFNC (median 60.75 hrs [5-621.5 hrs] versus 10.5 hrs [1-29 hrs], P < .0001). The OR of the PCO2 ≥ 55 mmHg for failure was 2.97 (95% CI; 1.08-8.17; P = .035). No patient died and no complications were recorded. Conclusion: The percentage success observed was similar to that published. In this sample, the failure of HFNC was only associated with an initial pCO2 ≥ 55 mmHg. On there being no complications reported as regards it use, it is considered safe, although a randomised, controlled, multicentre study is required to compare and contrast these results.

Selection of metal oxide charge transport layers for colloidal quantum dot LEDs.

We investigate the effect of the electronic energy level positioning, conductivity, and morphology of metal oxide charge transport layers on the performance of light emitting devices (LEDs) that consist of a colloidally synthesized quantum dot (QD) luminescent film embedded between electron and hole injecting ceramic layers. We demonstrate that understanding of these material properties and their effect on charging processes in QDs enables the systematic design of higher efficiency QD-LEDs and excitation of QDs with different emission colors using the same device structure.

HDAC inhibitor-based therapies and haematological malignancy.

Reversible acetylation mediated by histone deacetylase (HDAC) influences a broad repertoire of physiological processes, many of which are aberrantly controlled in tumour cells. Since HDAC inhibition prompts tumour cells to enter apoptosis, small-molecule HDAC inhibitors have been developed as a new class of mechanism-based anticancer agent, many of which have entered clinical trials. While the clinical picture is evolving and the precise utility of HDAC inhibitors remains to be determined, it is noteworthy that certain tumour types undergo a favourable response, in particular haematological malignancies. Vorinostat (suberoylanilide hydroxamic acid) has been approved for treating cutaneous T-cell lymphoma in patients with progressive, persistent or recurrent disease. Here, we discuss developments in our understanding of molecular events that underlie the anticancer effects of HDAC inhibitors and relate this information to the emerging clinical picture for the application of HDAC inhibitors in haematological malignancies.

Parenting programmes: a systematic review and synthesis of qualitative research.

BACKGROUND: Parenting programmes are at the heart of intervention strategies for parents of children with emotional and behaviour problems. Systematic reviews and meta-analyses of randomized controlled trials have indicated that such programmes can improve many aspects of family life. However, there is currently a dearth of information concerning what it is that makes parenting programmes meaningful and helpful to parents. The aim of this paper was to examine parents' experience and perceptions of parenting programmes using the meta-ethnographic method, in order to sensitize policymakers and practitioners to the key factors that parents perceive to be of value. METHODS: Systematic searches of a number of electronic databases were undertaken using key search terms. Critical appraisal of included studies was conducted using standardized criteria, and the reports were synthesized using meta-ethnographic methods. RESULTS: Six reports were purposefully selected and critically appraised independently by two reviewers. Two were excluded. Based on the remaining four papers, five key concepts were identified as important when planning and delivering parenting programmes. A lines-of-argument synthesis was developed which suggests that the acquisition of knowledge, skills and understanding, together with feelings of acceptance and support from other parents in the parenting group, enabled parents to regain control and feel more able to cope. This led to a reduction in feelings of guilt and social isolation, increased empathy with their children and confidence in dealing with their behaviour. CONCLUSION: This evaluation provides an indication of the components that parents perceive to be necessary in the provision of parenting programmes, independent of the particular type of programme being provided. It may therefore aid policymakers in decisions about which programmes to provide.

Women and minorities in orthopaedic residency programs.

Women and underrepresented minorities make up smaller proportions of orthopaedic residency programs than their numbers in medical school would predict, according to our evaluation of self-reported orthopaedic residency data from 1998 and 2001, as well as information on medical students published in 2002. Based on race, ethnicity, and sex, comparisons were made between students entering and graduating from medical school and those in orthopaedic residency programs. With few exceptions, the percentages of women and underrepresented minorities were statistically significantly lower among those training in orthopaedic residency programs compared with those same groups entering and graduating from medical school. The percentage of women and minorities in orthopaedic residency programs remained constant between 1998 and 2001. Further study is necessary to determine whether fewer students of color and women apply to orthopaedic residency programs because of lack of interest, lack of appropriate mentoring and role models, or other factors.

Epstein-Barr virus-encoded EBNA1 regulates cellular gene transcription and modulates the STAT1 and TGFbeta signaling pathways.

The Epstein-Barr virus (EBV)-encoded EBNA1 protein is expressed in all virus-associated tumors where it plays an essential role in the maintenance, replication and transcription of the EBV genome. Transcriptional profiling of EBNA1-expressing carcinoma cells demonstrated that EBNA1 also influences the expression of a range of cellular genes including those involved in translation, transcription and cell signaling. Of particular interest was the ability of EBNA1 to enhance expression of STAT1 and sensitize cells to interferon-induced STAT1 activation with resultant enhancement of major histocompatibility complex expression. A negative effect of EBNA1 on the expression of TGFbeta1-responsive betaig-h3 and PAI-1 genes was confirmed at the protein level in EBV-infected carcinoma cells. This effect resulted from the ability of EBNA1 to repress TGFbeta1-induced transcription via a reduction in the interaction of SMAD2 with SMAD4. More detailed analysis revealed that EBNA1 induces a lower steady-state level of SMAD2 protein as a consequence of increased protein turnover. These data show that EBNA1 can influence cellular gene transcription resulting in effects that may contribute to the development of EBV-associated tumors.

Assessing immune function in adult bronchiectasis.

Bronchiectasis is characterized by chronic airway infection and damage and remains an important health problem. Recent literature has emphasized the role of host defence and immune deficiency in the pathogenesis of bronchiectasis, but there have been few studies of immune function in adult bronchiectasis. A comprehensive screen of immune function was conducted in 103 adult patients with bronchiectasis, encompassing full blood examinations, immunoglobulins and IgG isotypes, complement levels, lymphocyte subsets and neutrophil function. Full blood examinations were normal in this cohort, as were complement levels. Statistical analysis confirmed that a significant number of subjects had low levels of IgG3 (13 patients), B cell lymphocytes (six patients) and T helper cell lymphocytes (seven patients) when compared with controls (P<0.05). The most common abnormality was found with testing of the neutrophil oxidative burst. All subjects had a normal neutrophil phagocytic function but 33 of the subjects had an oxidative burst that was below the normal range (P<0001). Almost half the group (45 subjects) had abnormally low levels of one of these four parameters. The findings of low B cells, Th cells and oxidative burst in bronchiectasis are novel. The results emphasize the importance of immune function assessment for adult bronchiectasis.

N-Alkyl-N-arylmethylpiperidin-4-amines: novel dual inhibitors of serotonin and norepinephrine reuptake.

A series of N-alkyl-N-arylmethylpiperidin-4-amines have been prepared and are demonstrated to be inhibitors of both serotonin and norepinephrine reuptake.

The treatment of crossbones of the hand.

Over a thirty-year period at Loma Linda University, we have seen eight patients with nine crossbones of the hand. These patients fall into the group of central deficiency with a cleft hand and central polydactyly. As will be noted in the paper, these two conditions may have a similar developmental relationship. Although the literature in the past specifies mainly one option - to remove the crossbone - we consider several different options that one should think about before removal of the crossbones.

Duplicated longitudinal bracketed epiphysis 'kissing delta phalanx' in the hand.

The duplicated longitudinal bracketed epiphysis ("kissing delta") phalanx has been described rarely. These delta bones have a bizarre appearance and are often associated with other developmental abnormalities such as central polydactyly. We have seen a total of 13 kissing delta phalanges in the hands. We discuss their natural history, look at the associated anomalies and consider the treatment options for this very rare congenital anomaly.

The genome sequence of Schizosaccharomyces pombe.

We have sequenced and annotated the genome of fission yeast (Schizosaccharomyces pombe), which contains the smallest number of protein-coding genes yet recorded for a eukaryote: 4,824. The centromeres are between 35 and 110 kilobases (kb) and contain related repeats including a highly conserved 1.8-kb element. Regions upstream of genes are longer than in budding yeast (Saccharomyces cerevisiae), possibly reflecting more-extended control regions. Some 43% of the genes contain introns, of which there are 4,730. Fifty genes have significant similarity with human disease genes; half of these are cancer related. We identify highly conserved genes important for eukaryotic cell organization including those required for the cytoskeleton, compartmentation, cell-cycle control, proteolysis, protein phosphorylation and RNA splicing. These genes may have originated with the appearance of eukaryotic life. Few similarly conserved genes that are important for multicellular organization were identified, suggesting that the transition from prokaryotes to eukaryotes required more new genes than did the transition from unicellular to multicellular organization.