Background & Aims: Childhood-onset inflammatory bowel disease (IBD) might be etiologically different from adult-onset IBD. We analyzed disease phenotypes and progression of childhood-onset disease ...and compared them with characteristics of adult-onset disease in patients in Scotland. Methods: Anatomic locations and behaviors were assessed in 416 patients with childhood-onset (276 Crohn's disease CD, 99 ulcerative colitis UC, 41 IBD type unclassified IBDU diagnosed before seventeenth birthday) and 1297 patients with adult-onset (596 CD, 701 UC) IBD using the Montreal classification. Results: At the time of diagnosis in children, CD involved small bowel and colon (L3) in 51% (138/273), colon (L2) in 36%, and ileum (L1) in 6%; the upper gastrointestinal (GI) tract (L4) was also affected in 51%. In 39%, the anatomic extent increased within 2 years. Behavioral characteristics progressed; 24% of children developed stricturing or penetrating complications within 4 years (vs 9% at diagnosis; P < .0001; odds ratio OR, 3.32; 95% confidence interval CI, 1.86–5.92). Compared with adults, childhood-onset disease was characterized by a “panenteric” phenotype (ileocolonic plus upper GI L3+L4; 43% vs 3%; P < .0001; OR, 23.36; 95% CI, 13.45–40.59) with less isolated ileal (L1; 2% vs 31%; P < .0001; OR, 0.06; 95% CI, 0.03–0.12) or colonic disease (L2; 15% vs 36%; P < .0001; OR, 0.31; 95% CI, 0.21–0.46). UC was extensive in 82% of the children at diagnosis, versus 48% of adults ( P < .0001; OR, 5.08; 95% CI, 2.73–9.45); 46% of the children progressed to develop extensive colitis during follow-up. Forty-six percent of children with CD and 35% with UC required immunomodulatory therapy within 12 months of diagnosis. The median time to first surgery was longer in childhood-onset than adult-onset patients with CD (13.7 vs 7.8 years; P < .001); the reverse was true for UC. Conclusions: Childhood-onset IBD is characterized by extensive intestinal involvement and rapid early progression.
Familial hypercholesterolemia, a common genetic metabolic disorder characterized by high cholesterol levels, is involved in the development of atherosclerosis and other preventable diseases. Familial ...hypercholesterolemia can also cause tendinous abnormalities, such as thickening and xanthoma (tendon lipid accumulation) in the Achilles, which may impede tendon biomechanics. The objective of this study was to investigate the effect of cholesterol accumulation on the biomechanical performance of Achilles tendons, in vivo. 16 participants (10 men, 6 women; 37±6 years) with familial hypercholesterolemia, diagnosed with tendon xanthoma, and 16 controls (10 men, 6 women; 36±7 years) underwent Achilles biomechanical assessment. Achilles biomechanical data was obtained during preferred pace, shod, walking by analysis of lower limb kinematics and kinetics utilizing 3D motion capture and an instrumented treadmill. Gastrocnemius medialis muscle-tendon junction displacement was imaged using ultrasonography. Achilles stiffness, hysteresis, strain and force were calculated from displacement-force data acquired during loading cycles, and tested for statistical differences using one-way ANOVA. Statistical parametric mapping was used to examine group differences in temporal data. Participants with familial hypercholesterolemia displayed lower Achilles stiffness compared to the control group (familial hypercholesterolemia group: 87±20 N/mm; controls: 111±18 N/mm; p = 0.001), which appeared to be linked to Achilles loading rate rather than an increased strain (FH: 5.27±1.2%; controls: 4.95±0.9%; p = 0.413). We found different Achilles loading patterns in the familial hypercholesterolemia group, which were traced to differences in the centre of pressure progression that affected ankle moment. This finding may indicate that individuals with familial hypercholesterolemia use different Achilles loading strategies. Participants with familial hypercholesterolemia also demonstrated significantly greater Achilles hysteresis than the control group (familial hypercholesterolemia: 57.5±7.3%; controls: 43.8±10%; p<0.001), suggesting that walking may require a greater metabolic cost. Our results indicate that cholesterol accumulation could contribute to reduced Achilles function, while potentially increasing the chance of injury.
A major goal of evolutionary developmental biology is to discover general models and mechanisms that create the phenotypes of organisms. However, universal models of such fundamental growth and form ...are rare, presumably due to the limited number of physical laws and biological processes that influence growth. One such model is the logarithmic spiral, which has been purported to explain the growth of biological structures such as teeth, claws, horns, and beaks. However, the logarithmic spiral only describes the path of the structure through space, and cannot generate these shapes.
Here we show a new universal model based on a power law between the radius of the structure and its length, which generates a shape called a 'power cone'. We describe the underlying 'power cascade' model that explains the extreme diversity of tooth shapes in vertebrates, including humans, mammoths, sabre-toothed cats, tyrannosaurs and giant megalodon sharks. This model can be used to predict the age of mammals with ever-growing teeth, including elephants and rodents. We view this as the third general model of tooth development, along with the patterning cascade model for cusp number and spacing, and the inhibitory cascade model that predicts relative tooth size. Beyond the dentition, this new model also describes the growth of claws, horns, antlers and beaks of vertebrates, as well as the fangs and shells of invertebrates, and thorns and prickles of plants.
The power cone is generated when the radial power growth rate is unequal to the length power growth rate. The power cascade model operates independently of the logarithmic spiral and is present throughout diverse biological systems. The power cascade provides a mechanistic basis for the generation of these pointed structures across the tree of life.
Background
The COVID‐19 pandemic has disrupted routine hospital services globally. This study estimated the total number of adult elective operations that would be cancelled worldwide during the 12 ...weeks of peak disruption due to COVID‐19.
Methods
A global expert response study was conducted to elicit projections for the proportion of elective surgery that would be cancelled or postponed during the 12 weeks of peak disruption. A Bayesian β‐regression model was used to estimate 12‐week cancellation rates for 190 countries. Elective surgical case‐mix data, stratified by specialty and indication (surgery for cancer versus benign disease), were determined. This case mix was applied to country‐level surgical volumes. The 12‐week cancellation rates were then applied to these figures to calculate the total number of cancelled operations.
Results
The best estimate was that 28 404 603 operations would be cancelled or postponed during the peak 12 weeks of disruption due to COVID‐19 (2 367 050 operations per week). Most would be operations for benign disease (90·2 per cent, 25 638 922 of 28 404 603). The overall 12‐week cancellation rate would be 72·3 per cent. Globally, 81·7 per cent of operations for benign conditions (25 638 922 of 31 378 062), 37·7 per cent of cancer operations (2 324 070 of 6 162 311) and 25·4 per cent of elective caesarean sections (441 611 of 1 735 483) would be cancelled or postponed. If countries increased their normal surgical volume by 20 per cent after the pandemic, it would take a median of 45 weeks to clear the backlog of operations resulting from COVID‐19 disruption.
Conclusion
A very large number of operations will be cancelled or postponed owing to disruption caused by COVID‐19. Governments should mitigate against this major burden on patients by developing recovery plans and implementing strategies to restore surgical activity safely.
Antecedentes
La pandemia de COVID‐19 ha interrumpido los servicios hospitalarios habituales a nivel mundial. En este estudio se calculó el número total de operaciones electivas para adultos que se cancelarían en todo el mundo durante las 12 semanas de interrupción máxima debido a COVID’19.
Métodos
Se realizó un estudio global de respuestas de expertos para obtener proyecciones sobre la proporción de cirugía electiva que se cancelaría o pospondría durante las 12 semanas del pico máximo de disrupción. Se usó un modelo bayesiano de regresión beta para estimar las tasas de cancelación durante 12 semanas en 190 países. Se determinaron los datos de la casuística de casos quirúrgicos electivos, estratificados por especialidad e indicación (cáncer versus cirugía benigna). Esta casuística de casos se aplicó a volúmenes quirúrgicos a nivel de país. Las tasas de cancelación de las 12 semanas se aplicaron a estas cifras para calcular el total de operaciones suspendidas.
Resultados
La mejor estimación fue que 28.404.603 operaciones hubieran sido canceladas o pospuestas durante las 12 semanas del pico de disrupción por COVID‐19 (2.367.050 operaciones por semana). La mayoría hubieran sido operaciones por enfermedad benigna (90,2%, 25.638.922/28. 404. 603). La tasa de cancelación general en 12 semanas sería del 72,3%. A nivel mundial, el 81,7% (25.638.921/31.378.062) de la cirugía benigna, el 37,7% (2. 324.069/6.162.311) de la cirugía por cáncer y el 25,4% (441.611/1.735.483) de las cesáreas electivas hubieran sido canceladas o pospuestas. Si los países aumentan su volumen quirúrgico normal en un 20% después de la pandemia, se tardaría una mediana de 45 semanas para eliminar la acumulación de operaciones resultantes de la disrupción por COVID’19.
Conclusión
Se cancelará o pospondrá un número muy grande de operaciones debido a la disrupción causada por COVID‐19. Los gobiernos deberían mitigar esta importante carga para los pacientes mediante el desarrollo de planes de recuperación e implementando estrategias para reiniciar de manera segura la actividad quirúrgica.
A very large number of operations will be cancelled or postponed owing to disruption caused by COVID‐19. Governments should mitigate against this major burden on patients by developing recovery plans and implementing strategies to restore surgical activity safely.
A mountain to climb
This study was initiated to compare the temporal response of serum lipoprotein lipase-suppressing mediator (LSM) and tumor necrosis factor (TNF) in lipopolysaccharide (LPS) -infused or -injected ...rats. Serial blood samples were obtained over a 5-day period from rats implanted with vascular catheters. Control rats infused with saline exhibited no detectable LSM activity during the 5-day observation period. LPS administered either by injection or infusion (6 h or 5 d) resulted in detection of serum LSM and TNF activities during the early period of observation with the LSM temporal response (8 h) outlasting the TNF response (3 h). The LSM response lasted a little longer in LPS-infused rats than it did in injected rats, but in each case LSM activity was not detected in serum samples collected at or after 12 h post-LPS. Neither the duration nor the magnitude of the TNF response differed between LPS-infused vs. -injected rats. Despite similarities in the LSM and TNF pattern in all rats receiving LPS, lethality was greater in LPS-infused animals than it was in LPS-injected rats. The results indicate that differences in lethality between LPS-injected and -infused rats cannot be explained solely by a differential response of serum TNF.
Against Happiness Flanagan, Owen; LeDoux, Joseph E; Bingle, Bobby ...
05/2023
eBook
The "happiness agenda" is a worldwide movement that claims that
happiness is the highest good, happiness can be measured, and
public policy should promote happiness. Against Happiness
is a thorough ...and powerful critique of this program, revealing the
flaws of its concept of happiness and advocating a renewed focus on
equality and justice. Written by an interdisciplinary team of
authors, this book provides both theoretical and empirical analysis
of the limitations of the happiness agenda. The authors emphasize
that this movement draws on a parochial, Western-centric
philosophical basis and demographic sample. They show that
happiness defined as subjective satisfaction or a surplus of
positive emotions bears little resemblance to the richer and more
nuanced concepts of the good life found in many world traditions.
Cross-cultural philosophy, comparative theology, and social and
cultural psychology all teach that cultures and subcultures vary in
how much value they place on life satisfaction or feeling happy.
Furthermore, the ideas promoted by the happiness agenda can compete
with rights, justice, sustainability, and equality-and even conceal
racial and gender injustice. Against Happiness argues that
a better way forward requires integration of cross-cultural
philosophical, ethical, and political thought with critical social
science. Ultimately, the authors contend, happiness should be a
secondary goal-worth pursuing only if it is contingent on the
demands of justice.
Intensive antiplatelet therapy with three agents might be more effective than guideline treatment for preventing recurrent events in patients with acute cerebral ischaemia. We aimed to compare the ...safety and efficacy of intensive antiplatelet therapy (combined aspirin, clopidogrel, and dipyridamole) with that of guideline-based antiplatelet therapy.
We did an international, prospective, randomised, open-label, blinded-endpoint trial in adult participants with ischaemic stroke or transient ischaemic attack (TIA) within 48 h of onset. Participants were assigned in a 1:1 ratio using computer randomisation to receive loading doses and then 30 days of intensive antiplatelet therapy (combined aspirin 75 mg, clopidogrel 75 mg, and dipyridamole 200 mg twice daily) or guideline-based therapy (comprising either clopidogrel alone or combined aspirin and dipyridamole). Randomisation was stratified by country and index event, and minimised with prognostic baseline factors, medication use, time to randomisation, stroke-related factors, and thrombolysis. The ordinal primary outcome was the combined incidence and severity of any recurrent stroke (ischaemic or haemorrhagic; assessed using the modified Rankin Scale) or TIA within 90 days, as assessed by central telephone follow-up with masking to treatment assignment, and analysed by intention to treat. This trial is registered with the ISRCTN registry, number ISRCTN47823388.
3096 participants (1556 in the intensive antiplatelet therapy group, 1540 in the guideline antiplatelet therapy group) were recruited from 106 hospitals in four countries between April 7, 2009, and March 18, 2016. The trial was stopped early on the recommendation of the data monitoring committee. The incidence and severity of recurrent stroke or TIA did not differ between intensive and guideline therapy (93 6% participants vs 105 7%; adjusted common odds ratio cOR 0·90, 95% CI 0·67–1·20, p=0·47). By contrast, intensive antiplatelet therapy was associated with more, and more severe, bleeding (adjusted cOR 2·54, 95% CI 2·05–3·16, p<0·0001).
Among patients with recent cerebral ischaemia, intensive antiplatelet therapy did not reduce the incidence and severity of recurrent stroke or TIA, but did significantly increase the risk of major bleeding. Triple antiplatelet therapy should not be used in routine clinical practice.
National Institutes of Health Research Health Technology Assessment Programme, British Heart Foundation.
The outgrowth of the vertebrate tail is thought to involve the proliferation of regionalised stem/progenitor cell populations formed during gastrulation. To follow these populations over extended ...periods, we used cells from GFP-positive transgenic chick embryos as a source for donor tissue in grafting experiments. We determined that resident progenitor cell populations are localised in the chicken tail bud. One population, which is located in the chordoneural hinge (CNH), contributes descendants to the paraxial mesoderm, notochord and neural tube, and is serially transplantable between embryos. A second population of mesodermal progenitor cells is located in a separate dorsoposterior region of the tail bud, and a corresponding population is present in the mouse tail bud. Using heterotopic transplantations, we show that the fate of CNH cells depends on their environment within the tail bud. Furthermore, we show that the anteroposterior identity of tail bud progenitor cells can be reset by heterochronic transplantation to the node region of gastrula-stage chicken embryos.
The British public have been offered alternating periods of lockdown and relaxation of restrictions as part of the coronavirus disease 2019 (COVID-19) lockdown exit strategy.1 Extended periods of ...lockdown will increase economic and social damage, and each relaxation will almost certainly trigger a further epidemic wave of deaths. There is an alternative strategy: universal repeated testing.2 We recommend evaluation of weekly severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antigen testing of the whole population in an entire city as a demonstration site (preferably several towns and cities, if possible), with strict household quarantine after a positive test. PCR reagents should be obtained from manufacturers, rather than clinical test companies, and exempt from regulatory requirements on medical testing to limit costs and ensure supplies.
Orkney was a major cultural center during the Neolithic, 3800 to 2500 BC. Farming flourished, permanent stone settlements and chambered tombs were constructed, and long-range contacts were sustained. ...From ∼3200 BC, the number, density, and extravagance of settlements increased, and new ceremonial monuments and ceramic styles, possibly originating in Orkney, spread across Britain and Ireland. By ∼2800 BC, this phenomenon was waning, although Neolithic traditions persisted to at least 2500 BC. Unlike elsewhere in Britain, there is little material evidence to suggest a Beaker presence, suggesting that Orkney may have developed along an insular trajectory during the second millennium BC. We tested this by comparing new genomic evidence from 22 Bronze Age and 3 Iron Age burials in northwest Orkney with Neolithic burials from across the archipelago. We identified signals of inward migration on a scale unsuspected from the archaeological record: As elsewhere in Bronze Age Britain, much of the population displayed significant genome-wide ancestry deriving ultimately from the Pontic-Caspian Steppe. However, uniquely in northern and central Europe, most of the male lineages were inherited from the local Neolithic. This suggests that some male descendants of Neolithic Orkney may have remained distinct well into the Bronze Age, although there are signs that this had dwindled by the Iron Age. Furthermore, although the majority of mitochondrial DNA lineages evidently arrived afresh with the Bronze Age, we also find evidence for continuity in the female line of descent from Mesolithic Britain into the Bronze Age and even to the present day.
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