Prolonged survival after splenectomy in Wiskott-Aldrich syndrome: a case report

Wiskott-Aldrich syndrome is a rare X-linked immunodeficiency disorder that is characterized by a variable clinical phenotype. Matched donor bone marrow transplantation is currently the only curative therapeutic option. We present the case of a 24-year-old male who was diagnosed at the age of seven with Wiskott-Aldrich syndrome. He did not respond to intravenous gammaglobulin and he experienced recurrent pulmonary infections despite prophylactic antibiotics. The patient had no matched donor. At the age of nine, he was submitted to splenectomy and his platelet count was normalized. Fifteen years later, the patient remains asymptomatic with a normal platelet count. He is still receiving prophylactic antibiotics and no bleeding episodes or septic complications have been reported. This case demonstrates that splenectomy can represent a safe therapeutic option in selected WAS patients, provided that there is a tight follow-up program, patient education and adherence to guidelines regarding post-splenectomy prophylaxis

Global overview of the management of acute cholecystitis during the COVID-19 pandemic (CHOLECOVID study)

Background: This study provides a global overview of the management of patients with acute cholecystitis during the initial phase of the COVID-19 pandemic. Methods: CHOLECOVID is an international, multicentre, observational comparative study of patients admitted to hospital with acute cholecystitis during the COVID-19 pandemic. Data on management were collected for a 2-month study interval coincident with the WHO declaration of the SARS-CoV-2 pandemic and compared with an equivalent pre-pandemic time interval. Mediation analysis examined the influence of SARS-COV-2 infection on 30-day mortality. Results: This study collected data on 9783 patients with acute cholecystitis admitted to 247 hospitals across the world. The pandemic was associated with reduced availability of surgical workforce and operating facilities globally, a significant shift to worse severity of disease, and increased use of conservative management. There was a reduction (both absolute and proportionate) in the number of patients undergoing cholecystectomy from 3095 patients (56.2 per cent) pre-pandemic to 1998 patients (46.2 per cent) during the pandemic but there was no difference in 30-day all-cause mortality after cholecystectomy comparing the pre-pandemic interval with the pandemic (13 patients (0.4 per cent) pre-pandemic to 13 patients (0.6 per cent) pandemic; P = 0.355). In mediation analysis, an admission with acute cholecystitis during the pandemic was associated with a non-significant increased risk of death (OR 1.29, 95 per cent c.i. 0.93 to 1.79, P = 0.121). Conclusion: CHOLECOVID provides a unique overview of the treatment of patients with cholecystitis across the globe during the first months of the SARS-CoV-2 pandemic. The study highlights the need for system resilience in retention of elective surgical activity. Cholecystectomy was associated with a low risk of mortality and deferral of treatment results in an increase in avoidable morbidity that represents the non-COVID cost of this pandemic

Evaluation of a rotary regenerative burner for lean mixtures of gaseous fuels

Imperial Users onl

Some aspects of age-hardening, grain refinement, deformation and fracture in al-li based alloys

Aluminium-lithium alloys such as 8090 (Al-Li-Cu-Mg) have been developed with the aim of using them instead of conventional aluminium alloys such as 2024 (Al-Cu-Mg) and 7050 (Al-Zn-Mg-Cu) in order to save weight (by up to 10%), especially in aerospace structures. This aim has not, however, been achieved largely because the fracture resistance of Al-Li alloys is often inferior to conventional alloys, with Al-Li alloys being especially prone to low-energy intergranular fracture. Thus, Al-Li alloys have only been used in niche applications to date, such as for the external tank of the space shuttle and the fuselage skin and frames of a helicopter. Service experience for the latter showed that crashworthiness was poor due to the occurrence of brittle intergranular fracture, and the use of Al-Li alloys in this application has now been discontinued. Various hypotheses have been proposed to account for the poor intergranular fracture resistance of Al-Li alloys including: (i) a planar slip mode due to the presence of easily sheared δ' precipitates produced by age-hardening, which results in dislocation-pileups and high stress concentrations at grain boundaries, and (ii) lithium segregation at grain boundaries which weakens interatomic bonding across boundaries. One of the aims of the present work was to resolve controversies regarding the cause(s) of brittle intergranular fracture. Another aim was to determine if grain refinement by severe-plastic-deformation processes (friction-stir processing, high-pressure torsion, and equal-angle channel pressing) increased the fracture resistance and strength, without compromising other properties such as the age-hardening response. A wide range of techniques was used to characterise the microstructures, slip characteristics, and fracture-surface appearance, including: (i) optical microscopy (OM), (ii) scanning electron microscopy (SEM), (iii) transmission electron microscopy (TEM), and (iv) atom-probe tomography (for direct measurements of grain-boundary segregation). Other techniques used (to a lesser extent) included: (i) atomic force microscopy (AFM), (ii) scanning laser confocal microscopy (SLCM), and (iii) electron backscattered diffraction (EBSD). A range of Al-Li alloys with varying Li contents were tested and compared with other aluminium alloys, e.g. Al-Mg alloys with varying Mg contents, and with a nickel-base superalloy (Waspaloy) with easily sheared, coherent L12 γ' precipitates, analogous to the coherent δ' precipitates in Al-Li alloys. Since the work involved several aims and used a wide variety of techniques and alloys, separate results followed by a discussion have been written for (i) the effects of severe-plastic-deformation processing on microstructures, (ii) the effect of grain size on age-hardening, (iii) the fracture behaviour with respect to slip characteristics and solute content, and (iv) grain-boundary segregation. These topics are, of course, interconnected, but the above layout of the thesis makes it easier to follow than combining all the results into one section followed by one discussion section. The major aims of the work have largely been achieved, with the observations (and a critical review of the literature) showing that planar slip is not an important factor in promoting brittle intergranular fracture. Rather, it appears that lithium segregation (leading to a specific temperature-dependent 2-D structure) at grain boundaries, in conjunction with strain localisation in precipitate-free zones at grain boundaries, is mainly responsible for brittle intergranular fracture in commercial alloys (with low levels of alkali-metal impurities). For example, brittle intergranular fracture was observed at low testing temperatures for a mechanically alloyed 5091 alloy that exhibited homogeneous slip, and transitions to ductile transgranular fracture occurred with increasing temperature despite no changes in slip mode. For the nickel base superalloy, marked slip planarity was observed, but fractures were transgranular and ductile (at 20°C and -196°C). Numerous other observations also showed that there was no correlation between slip morphology and fracture behaviour. Direct evidence for lithium segregation at grain boundaries using atom-probe tomography was not obtained, probably because preferential field-evaporation of lithium (due to its low atomic number) occurred at grain boundaries. However, only a limited number of grain boundaries were examined since atom-probe tips often fractured (presumably at grain boundaries weakened by segregation) prior to collecting sufficient data for analysis. Magnesium segregation at grain boundaries was detected in some alloys (and has been reported in the literature for other alloys), and probably also results in grain-boundary embrittlement. Thus, results obtained in the present work, along with those from previous work, showed that the tendency for brittle intergranular fracture increased with (i) increase in Mg contents in Al-Mg alloys, and (ii) increasing Mg + Li contents in Al-Li-Mg alloys. Theoretical considerations discussed in the literature suggest that both Li and Mg segregation at grain boundaries in Al alloys should promote brittle intergranular fracture. The present work showed that brittle intergranular fracture was suppressed in 8090 alloys with ultra-fine grain sizes produced by friction stir processing  work which involved establishing the processing conditions required for the production of ultra-fine grain sizes. The transition from brittle intergranular fracture in coarse-grained material to ductile dimpled fractures in ultra-fine grained material was probably due to the fragmentation of coarse constituent particles (resulting in numerous, small, dispersed particles that acted as a void-nucleation sites) along with an increase in the volume fraction of precipitate-free zones at grain boundaries. The age-hardening response of grain-refined material was significantly different from that in coarse-grained material for the 8090 alloy, and such differences would need to be borne in mind if ultra-fine grained material were to be used. For example, for the 8090 alloy processed by high-pressure torsion to a grain size ~170 nm, the initial hardness was high (VH ~200) due to grain-size strengthening according to the Hall-Petch relationship, but decreased with ageing time (at the high ageing temperatures of 170 to 200°C) because softening due to grain growth was more dominant than hardening due to precipitation. For friction-stir processed material, with a 600 nm grain size, precipitation-hardening was observed, but the peak-hardness was less than that for the coarse-grained material (despite some grain-size strengthening) due to a larger volume fraction of precipitate-free zone at grain boundaries. While most of the objectives of present work were achieved, there are quite a few ‘loose ends’, and further work is recommended in regard to (i) a more complete characterisation of microstructures after severe plastic deformation for different techniques and processing variables, (ii) further atom-probe and high-resolution transmission electron microscopy to try to detect lithium segregation at grain boundaries, and (ii) the effect of ultra-fine grain and nanocrystalline grain sizes on fracture behaviour. The incompleteness of some of the above topics is largely because it was decided it was better to obtain a broad overview of the issues, using a wide variety of experimental techniques, rather than concentrate on one particular material and processing technique

Ο ρόλος της συμπληρωματικής θυρεοειδεκτομής σε ανεύρεση καρκινώματος μετά από ημιθυρεοειδεκτομή

Η αύξηση της επίπτωσης του καλώς διαφοροποιημένου θυρεοειδικού καρκίνου και ιδίως του θηλώδους καρκινώματος τις τελευταίες τρεις δεκαετίες, είτε αφορά σε αληθή επίπτωση είτε αφορά σε υπερδιάγνωση λόγω της εξέλιξης των απεικονιστικών μεθόδων, οδήγησε την ιατρική κοινότητα σε χαλάρωση των κριτηρίων όσον αφορά την θεραπευτική αντιμετώπισή του. Η ημιθυρεοειδεκτομή κερδίζει τα τελευταία χρόνια έδαφος στην αντιμετώπιση του καλώς διαφοροποιημένου καρκίνου και συστήνεται πλέον σε όγκους έως 4cm χωρίς εξωθυρεοειδική διήθηση ή λεμφαδενικές μεταστάσεις, εφόσον ο ασθενής δεν έχει ιστορικό έκθεσης σε ιονίζουσα ακτινοβολία στον τράχηλο ή οικογενειακό ιστορικό καρκίνου θυρεοειδούς. Επίσης, η ημιθυρεοειδεκτομή μπορεί να είναι διαγνωστική σε περιπτώσεις αδιευκρίνιστης παθολογίας στην FNA (AUS / FLUS ή FN / SFN). Το ποσοστό των ασθενών που χρήζουν συμπληρωματικής θυρεοειδεκτομής φαίνεται πως μειώνεται τα τελευταία έτη, εφόσον ακολουθούνται οι κατευθυντήριες οδηγίες, ωστόσο τουλάχιστον το 25% των ασθενών χρειάζονται επανεπέμβαση για την επίτευξη ριζικού ογκολογικού αποτελέσματος. Στην παρούσα διπλωματική εργασία έγινε λεπτομερής ανασκόπηση της σύγχρονης βιβλιογραφίας όσον αφορά στα νεότερα δεδομένα του θυρεοειδικού καρκίνου και ιδίως του καλώς διαφοροποιημένου, στις ενδείξεις της ημιθυρεοειδεκτομής και στην τάση των χειρουργών ενδοκρινών αδένων να την επιλέγουν όταν και όπου χρειάζεται, καθώς και στο ρόλο της συμπληρωματικής θυρεοειδεκτομής, τις ενδείξεις και τις αντενδείξεις της, τα ποσοστά επιπλοκών και τον κατάλληλο χρόνο διενέργειάς της.The increasing incidence of well-differentiated thyroid cancer and especially papillary carcinoma over the last three decades, whether due to a true incidence or overdiagnosis due to the development of imaging methods, has led the medical community to loose the treatmnet criteria. Hemithyroidectomy has gained ground in recent years in the treatment of well-differentiated cancer and is now recommended in tumors up to 4 cm without extrathyroid infiltration or lymph node metastases, as long as the patient has no history of exposure to ionizing radiation in the cervix or familial thyroid tissue. Also, hemithyroidectomy can be diagnostic in cases of undetermined pathology in the FNA (AUS / FLUS or FN / SFN). The proportion of patients who need completion thyroidectomy seems to be declining in recent years, as long as the guidelines are followed, however at least 25% of patients need reoperation to achieve a radical oncological result. In the present dissertation, a detailed review of the current literature has been made regarding the latest data on thyroid cancer, especially the well-differentiated, the indications for hemithyroidectomy and the tendency of endocrine surgeons to select it when and where necessary, as well as the role of completion thyroidectomy , its indications and contraindications, complication rates and the appropriate time to perform it

Some aspects of age-hardening, grain refinement, deformation and fracture in al-li based alloys

Aluminium-lithium alloys such as 8090 (Al-Li-Cu-Mg) have been developed with the aim of using them instead of conventional aluminium alloys such as 2024 (Al-Cu-Mg) and 7050 (Al-Zn-Mg-Cu) in order to save weight (by up to 10%), especially in aerospace structures. This aim has not, however, been achieved largely because the fracture resistance of Al-Li alloys is often inferior to conventional alloys, with Al-Li alloys being especially prone to low-energy intergranular fracture. Thus, Al-Li alloys have only been used in niche applications to date, such as for the external tank of the space shuttle and the fuselage skin and frames of a helicopter. Service experience for the latter showed that crashworthiness was poor due to the occurrence of brittle intergranular fracture, and the use of Al-Li alloys in this application has now been discontinued. Various hypotheses have been proposed to account for the poor intergranular fracture resistance of Al-Li alloys including: (i) a planar slip mode due to the presence of easily sheared δ' precipitates produced by age-hardening, which results in dislocation-pileups and high stress concentrations at grain boundaries, and (ii) lithium segregation at grain boundaries which weakens interatomic bonding across boundaries. One of the aims of the present work was to resolve controversies regarding the cause(s) of brittle intergranular fracture. Another aim was to determine if grain refinement by severe-plastic-deformation processes (friction-stir processing, high-pressure torsion, and equal-angle channel pressing) increased the fracture resistance and strength, without compromising other properties such as the age-hardening response. A wide range of techniques was used to characterise the microstructures, slip characteristics, and fracture-surface appearance, including: (i) optical microscopy (OM), (ii) scanning electron microscopy (SEM), (iii) transmission electron microscopy (TEM), and (iv) atom-probe tomography (for direct measurements of grain-boundary segregation). Other techniques used (to a lesser extent) included: (i) atomic force microscopy (AFM), (ii) scanning laser confocal microscopy (SLCM), and (iii) electron backscattered diffraction (EBSD). A range of Al-Li alloys with varying Li contents were tested and compared with other aluminium alloys, e.g. Al-Mg alloys with varying Mg contents, and with a nickel-base superalloy (Waspaloy) with easily sheared, coherent L12 γ' precipitates, analogous to the coherent δ' precipitates in Al-Li alloys. Since the work involved several aims and used a wide variety of techniques and alloys, separate results followed by a discussion have been written for (i) the effects of severe-plastic-deformation processing on microstructures, (ii) the effect of grain size on age-hardening, (iii) the fracture behaviour with respect to slip characteristics and solute content, and (iv) grain-boundary segregation. These topics are, of course, interconnected, but the above layout of the thesis makes it easier to follow than combining all the results into one section followed by one discussion section. The major aims of the work have largely been achieved, with the observations (and a critical review of the literature) showing that planar slip is not an important factor in promoting brittle intergranular fracture. Rather, it appears that lithium segregation (leading to a specific temperature-dependent 2-D structure) at grain boundaries, in conjunction with strain localisation in precipitate-free zones at grain boundaries, is mainly responsible for brittle intergranular fracture in commercial alloys (with low levels of alkali-metal impurities). For example, brittle intergranular fracture was observed at low testing temperatures for a mechanically alloyed 5091 alloy that exhibited homogeneous slip, and transitions to ductile transgranular fracture occurred with increasing temperature despite no changes in slip mode. For the nickel base superalloy, marked slip planarity was observed, but fractures were transgranular and ductile (at 20°C and -196°C). Numerous other observations also showed that there was no correlation between slip morphology and fracture behaviour. Direct evidence for lithium segregation at grain boundaries using atom-probe tomography was not obtained, probably because preferential field-evaporation of lithium (due to its low atomic number) occurred at grain boundaries. However, only a limited number of grain boundaries were examined since atom-probe tips often fractured (presumably at grain boundaries weakened by segregation) prior to collecting sufficient data for analysis. Magnesium segregation at grain boundaries was detected in some alloys (and has been reported in the literature for other alloys), and probably also results in grain-boundary embrittlement. Thus, results obtained in the present work, along with those from previous work, showed that the tendency for brittle intergranular fracture increased with (i) increase in Mg contents in Al-Mg alloys, and (ii) increasing Mg + Li contents in Al-Li-Mg alloys. Theoretical considerations discussed in the literature suggest that both Li and Mg segregation at grain boundaries in Al alloys should promote brittle intergranular fracture. The present work showed that brittle intergranular fracture was suppressed in 8090 alloys with ultra-fine grain sizes produced by friction stir processing  work which involved establishing the processing conditions required for the production of ultra-fine grain sizes. The transition from brittle intergranular fracture in coarse-grained material to ductile dimpled fractures in ultra-fine grained material was probably due to the fragmentation of coarse constituent particles (resulting in numerous, small, dispersed particles that acted as a void-nucleation sites) along with an increase in the volume fraction of precipitate-free zones at grain boundaries. The age-hardening response of grain-refined material was significantly different from that in coarse-grained material for the 8090 alloy, and such differences would need to be borne in mind if ultra-fine grained material were to be used. For example, for the 8090 alloy processed by high-pressure torsion to a grain size ~170 nm, the initial hardness was high (VH ~200) due to grain-size strengthening according to the Hall-Petch relationship, but decreased with ageing time (at the high ageing temperatures of 170 to 200°C) because softening due to grain growth was more dominant than hardening due to precipitation. For friction-stir processed material, with a 600 nm grain size, precipitation-hardening was observed, but the peak-hardness was less than that for the coarse-grained material (despite some grain-size strengthening) due to a larger volume fraction of precipitate-free zone at grain boundaries. While most of the objectives of present work were achieved, there are quite a few ‘loose ends’, and further work is recommended in regard to (i) a more complete characterisation of microstructures after severe plastic deformation for different techniques and processing variables, (ii) further atom-probe and high-resolution transmission electron microscopy to try to detect lithium segregation at grain boundaries, and (ii) the effect of ultra-fine grain and nanocrystalline grain sizes on fracture behaviour. The incompleteness of some of the above topics is largely because it was decided it was better to obtain a broad overview of the issues, using a wide variety of experimental techniques, rather than concentrate on one particular material and processing technique

Σύνθεση δευτερογενών μεταβολιτών της τυροσίνης του σπόγγου ianthella basta: πρώτη ολική ασύμμετρη σύνθεση της βασταδίνης 12

In the current Ph.D. thesis the first total synthesis of Bastadin 12 is presented. Bastadin 12, as well as the other members of the bastadin family, was isolated from the sponges of the order Ιanthella and Psammaplysilla and exhibits anticancer activity against P-388 and other human cancer lines, antimicrobial activity against the Gram-positive E. faecalis και S. aureus bacteria, while bastadins 5 and 10 have been studied towards their efficacy as intracellular calcium channel modulators. The synthesis was completed after 35 reactions, 4.3% overall, based on a flexible retro-synthetic scheme. In this way, besides Bastadin 12, the other members of the bastadin family may be synthesized as well from an advanced common intermediate. Key element of the synthetic scheme is the iodonium salt mediated diaryl ether synthesis, and the construction of the macrocyclic bastarane ring, through a macrolactamization process. The isomerization of the E- Z- dioxime to the E- E- isomer, which is found in the natural product, is still under investigation.Στην παρούσα διδακτορική διατριβή παρουσιάζεται η πρώτη ολική σύνθεση της Βασταδίνης 12. Η Βασταδίνη 12, όπως και τα υπόλοιπα μέλη της οικογένειας των Βασταδινών, απομονώθηκε από τους σπόγγους του γένους Ianthella και Psammaplysilla και αποτελεί αναστολέα της κυτταρικής σειράς Ρ-388 και άλλων ανθρώπινων καρκινικών κυτταρικών σειρών, και αναστολέα των κατά Gram θετικών βακτηρίων E. faecalis και S. aureus, ενώ οι Βασταδίνες 5 και 10 έχουν μελετηθεί ως προς την ικανότητά τους να ρυθμίζουν τα ενδοκυττάρια κανάλια ασβεστίου. Η σύνθεση ολοκληρώθηκε μετά από 35 στάδια, με 4.3% συνολική απόδοση, και μπορεί με μικρές μετατροπές σε αρχικά ή προχωρημένα στάδια της συνθετικής πορείας, να χρησιμοποιηθεί ως γενική μέθοδος παρασκευής των μελών της οικογένειας των Βασταδινών. Στάδιο “κλειδί” του συνθετικού σχήματος αποτελεί ο σχηματισμός των διαρυλοαιθερικών τμημάτων, μέσω αντίδρασης σύζευξης του κατάλληλου φαινολικού υποστρώματος με το δις-(2-βενζυλοξυ-5-φορμυλο-φαινυλο)-ιωδωνιακό βρωμίδιο, καθώς και η αντίδραση μακρολακταμοποίησης μέσω της οποίας συντέθηκε ο μακροκυκλικός βασταρανικός δακτύλιος. Στοιχείο που αποτελεί ακόμα αντικείμενο μελέτης είναι η δυνατότητα ισομερείωσης της Ε- Ζ- διοξίμης στο Ε- Ε- ισομερές, το οποίο απαντάται στο φυσικό προϊόν

ELECTRONIC STRUCTURE OF HEMIN AND HEMOGLOBINS.

ELECTRONIC STRUCTURE OF HEMIN AND HEMOGLOBINS

Challenges in Developing High Performance Al-Li Alloys

The goal of replacing \u27conventional\u27 Al alloys with Al-Li alloys to reduce weight of aerospace structures has had only limited success to date, despite one of the largest alloy-development programs ever undertaken. One of the reasons being, for some product forms and crack-plane orientations, fracture toughness is lower compared with conventional Al alloys due to a greater propensity for low-energy intergranular fracture. Proposed explanations for brittle intergranular fracture include: (i) planar slip resultingin high stresses where slip bands impinge on grain-boundaries, (ii) embrittlement due to alkali-metal-impurity phases, and (iii) grain-boundary structural changes associated with segregation of lithium. The present paper reviews evidence for and against these proposed mechanisms based on (i) studies of 8090 and 2090 alloys, and the more recently developed 2297 alloy, and (ii) comparisons of fracture of these alloys with other materials that exhibit grain-boundary weakness. It appears that lithium segregation to grain boundaries is the prime cause of low-energy intergranular fracturein Al-Li alloys. Embrittlement by alkali-metal impurities is not important providing that impurity levels are less than about 5 ppm (as is the case for most commercially produced alloys). Planar slip and other factors probably play only a minor role