‘Down-shifting’ among top UK scientists? – The decline of ‘revolutionary science’ and the rise of ‘normal science’ in the UK compared with the USA

It is sometimes asserted that UK science is thriving, at other times that it has declined. We suggest that both assertions are partly true because the UK is thriving with respect to the volume of 'normal' science production but at the same time declining in the highest level of 'revolutionary' science. Revolutionary science may be distinguished from normal science in that revolutionary science aims at generating qualitative advances which change the direction of established science, while 'normal' science aims at incremental progress extrapolating from established science. Revolutionary science has been measured by counting national numbers of science Nobel laureates and ISI Highly Cited (HiCi) scientists; normal science has been measured using the total volume of scientific publications and citations at both national and institutional levels. By these criteria the UK has been progressively catching-up with the USA in terms of normal science since the 1990s. At the same time the UK has declined in revolutionary science over recent decades by a significant brain drain of future Nobel laureates and HiCi scientists, and a sharply reduced success (both in absolute and compared with the USA) at winning science Nobel prizes. One possible cause for this pattern could be a time-lag, such that the UK's improved science production since about 1990 may eventually work-through into improved UK performance in revolutionary science. More pessimistically, this pattern may reflect a strategic down-shift of the best UK-resident scientists away from revolutionary science and towards less-ambitious and safer normal science which is more productive in the short term.     

Postnatal stress in mice: Does “stressing” the mother have the same effect as “stressing” the pups?

Short- and long-term effects of brief maternal separation, maternal exposure to novel male odor, and standard rearing were compared in NMRI mice. The first condition consisted of 15 min of daily exposure of pups to clean bedding (CB), and the second condition consisted of 15 min of mothers' exposure to the odor of strange males (SM), for 14 days after birth starting from postnatal Day 1. Thus, both conditions entailed the same period of maternal separation. A control mother-offspring group was left undisturbed (nonhandled, N-H). Corticosterone levels of mothers and pups were measured at the end of the last manipulation session. Corticosterone levels were higher in SM mothers, differing from both those of CB and of control dams; CB pups showed the highest corticosterone levels in comparison with the pups belonging to the other groups. Maternal behavior observed as furthest as possible from the daily separation session did not differ among the three groups. The behavioral response to 0.5 mg/kg of apomorphine in 15-day-old pups was enhanced in both CB and SM animals, which suggests an alteration of dopaminergic functioning. Finally, adult CB and SM male mice showed an increase in the percentage of time and entries into the open arms of the plus-maze in comparison to nonhandled males. This study indicates that exposure to ecologically relevant stimuli elicited a stress response in lactating dams. This "social stress" brings about short- and long-term effects in the offspring, even in the absence of any direct manipulation of the pups.     

Estimation of<Emphasis Type="Italic"> V̇</Emphasis>O<Subscript>2max</Subscript> from the ratio between HR<Subscript>max </Subscript>and HR<Subscript>rest</Subscript> – the Heart Rate Ratio Method

The effects of ̇raining and/or ageing upon maximal oxygen uptake (O_2max) and heart rate values at rest (HR_rest) and maximal exercise (HR_max), respectively, suggest a relationship between O_2max and the HR_max-to-HR_rest ratio which may be of use for indirect testing of O_2max. Fick principle calculations supplemented by literature data on maximum-to-rest ratios for stroke volume and the arterio-venous O₂ difference suggest that the conversion factor between mass-specific O_2max (ml·min^–1·kg^–1) and HR_max·HR_rest ^–1 is ~15. In the study we experimentally examined this relationship and evaluated its potential for prediction of O_2max. O_2max was measured in 46 well-trained men (age 21–51 years) during a treadmill protocol. A subgroup (n=10) demonstrated that the proportionality factor between HR_max·HR_rest ^–1 and mass-specific O_2max was 15.3 (0.7) ml·min^–1·kg^–1. Using this value, O_2max in the remaining 36 individuals could be estimated with an SEE of 0.21 l·min^–1 or 2.7 ml·min^–1·kg^–1 (~4.5%). This compares favourably with other common indirect tests. When replacing measured HR_max with an age-predicted one, SEE was 0.37 l·min^–1 and 4.7 ml·min^–1·kg^–1 (~7.8%), which is still comparable with other indirect tests. We conclude that the HR_max-to-HR_rest ratio may provide a tool for estimation of O_2max in well-trained men. The applicability of the test principle in relation to other groups will have to await direct validation. O_2max can be estimated indirectly from the measured HR_max-to-HR_rest ratio with an accuracy that compares favourably with that of other common indirect tests. The results also suggest that the test may be of use for O_2max estimation based on resting measurements alone.An erratum to this article can be found at     

The Genus Streptococcus – Part I: Emerging Pathogens in the “Pyogenic Cocci” and the “Streptococcus bovis” Groups

In this first part of a two-part update on the streptococci, new and emerging pathogens in the “pyogenic cocci group” and the “Streptococcus bovis group” are addressed. Among the pyogenic cocci, several new species have been described, and some of these are becoming relevant agents of human disease. Streptococcus porcinus and Streptococcus pseudoporcinus are β-hemolytic streptococci that are found in swine and humans, respectively. S. pseudoporcinus has been isolated primarily from the female genital tract and may play a role in genitourinary tract infections, wound infections, and adverse pregnancy outcomes. Streptococcus iniae, Streptococcus hongkongensis, and Streptococcus ictaluri are fish pathogens, and S. iniae, in particular, has been isolated from several human infections in persons who handle raw seafood or experience penetrating injuries from fish spines or crab pincers. Streptococcus gallolyticus subspecies (i.e., the former “S. bovis group”) are well-recognized causes of bacteremia, meningitis, and endocarditis. S. gallolyticus subsp. gallolyticus is known to be associated with colon cancer, and current studies suggest that other S. gallolyticus subspecies (particularly S. gallolyticus subsp. pasteurianus) may also be associated with meningitis and other digestive tract malignancies. In this review, current research on S. gallolyticus subspecies and proposed mechanisms for their involvement in the pathogenesis of colonic carcinoma are also briefly addressed.     

Do the public share practitioners’ views about the best evidence?

Objective

To investigate whether general practitioners (GPs) and patients agree on what constitutes the best evidence for the effectiveness of treatments.

Methods

GPs and members of the public aged 18–83 read five scenarios describing comparisons between hypothetical treatments for common ailments. Each scenario reported that one treatment was the more effective, as determined by randomised controlled trial (RCT), audit of treatment outcomes from many doctors’ patients, a single doctor's clinical experience, a friend's experience, or a web-based sales site. Participants rated how confident they would be that the treatment reported to be more effective would work for them.

Results

All participants had least confidence in the web-based sales site, more confidence in a friend's experience and more still in one doctor's experience. For doctor's experience, audit and RCT, amongst the public there were some differences by age but, importantly, only GPs had most confidence in evidence from an RCT.

Conclusion

GPs may treat evidence from RCTs as the gold standard while members of the public (their patients) may not afford it that same respect.

Practice implications

GPs engaged in shared decision-making should be alert to possible differences from their patients in the weight given to different types of evidence.     

Is the genus<Emphasis Type="Italic"> Digramma</Emphasis> synonymous to the genus<Emphasis Type="Italic"> Ligula</Emphasis> (Cestoda: Pseudophyllidea)?

The genus Digramma (Cestoda: Pseudophyllidea) described by Cholodkovsky in 1915 differs from the genus Ligula only by the number of the reproductive organs per proglottis. However, the occurrence of transitional forms in Digramma raises much confusion concerning its generic validity. In the present study, cestodes previously designated as Digramma and Ligula were collected from lakes in the lower and middle reaches of the Yangtze River, and also from Qinghai Lake on Qingzang plateau, China. The entire internal transcribed spacer of the ribosomal DNA (ITS rDNA) and 5' end of 28S rDNA were compared between the Digramma and Ligula specimens. The low level of nucleotide variation between the two genera may imply that cestodes in the genus Digramma are paraphyletic to the Ligula genus, and Digramma is a synonym of Ligula. However, whether previously identified Digramma cestodes represent different species in the genus Ligula requires further investigation.     

Methotrexate for the treatment of rheumatoid arthritis in the biologic era: Still an “anchor” drug?

The improvement of rheumatoid arthritis (RA) management has been strictly related to methotrexate (MTX) long-term effectiveness, safety profile and its widespread use in clinical practice over the last decades. According to the results of several head-to-head comparative trials against other synthetic DMARDs, MTX has been recognised as the “anchor drug” for the treatment of RA at the end of the 1990s. The subsequent increasing knowledge in the area of RA pathophysiology has progressively expanded the arsenal of available therapeutic tools, especially by the introduction of novel drugs such as biological DMARDs. The introduction of therapies targeted to key molecules and cells involved in RA pathogenesis has significantly changed the strategies for disease management, possibly modifying the key role of MTX. This review first analyses data supporting the evolution of MTX towards the role of “anchor drug” for RA in the pre-biologic era. We will then examine how the introduction and progressive spreading of biological agents could have modified the central role of MTX in the approach to RA.     

Expanding the phenotype of CRB2 mutations – A new ciliopathy syndrome?

Recessive CRB2 mutations were recently reported to cause both steroid resistant nephrotic syndrome and prenatal onset ventriculomegaly with kidney disease. We report two Ashkenazi Jewish siblings clinically diagnosed with ciliopathy. Both presented with severe congenital hydrocephalus and mild urinary tract anomalies. One affected sibling also has lung hypoplasia and heart defects. Exome sequencing and further CRB2 analysis revealed that both siblings are compound heterozygotes for CRB2 mutations p.N800K and p.Gly1036Alafs*43, and heterozygous for a deleterious splice variant in the ciliopathy gene TTCB21. CRB2 is a polarity protein which plays a role in ciliogenesis and ciliary function. Biallelic CRB2 mutations in animal models result in phenotypes consistent with ciliopathy. This report expands the phenotype of CRB2 mutations to include lung hypoplasia and uretero‐pelvic renal anomalies, and confirms cardiac malformation as a feature. We suggest that CRB2‐associated disease is a new ciliopathy syndrome with possible digenic/triallelic inheritance, as observed in other ciliopathies. Clinically, CRB2 should be assessed when ciliopathy is suspected, especially in Ashkenazi Jews, where we found that p.N800K carrier frequency is 1 of 64. Patients harboring CRB2 mutations should be tested for the complete range of ciliopathy manifestations.     

Oxygen inhibits—even though in traces—the hatching of the eggs of the liver fluke <Emphasis Type="Italic">Dicrocoelium dendriticum</Emphasis> R

A chamber was constructed to investigate the influence of gaseous surroundings on the hatching of Dicrocoelium eggs (Fig. 1). It was found that the exclusion of even traces of oxygen is the prerequisite for successful hatching. Oxygen was removed by baker’s yeast suspensions as well as by dithionite solutions. Hatching rates reached a maximum when the carbon dioxide content of the chamber ranged between 0.1% and 4%. Under natural hatching conditions within the intestine of the pulmonate intermediate hosts, bacteria ensure oxygen consumption and carbon dioxide production. The consequence is the hatching of Dicrocoelium eggs. Carbon monoxide also stimulates hatching in the presence of oxygen and therefore seems to block the inhibition mechanism, which is based on oxygen acting. The hatching of eggs started about 5 min after exposure to hatching conditions and continued over a period of 60–90 min. The experiments were occasionally carried out in 1974–1978 at the following institutes of the University of Hamburg: Zoologisches Institut und Zoologisches Museum, and Institut für Organische Chemie und Biochemie, Abt. Biochemie.     

Should the ‘no thumb technique’ be the golden standard for evaluating patellar tracking in total knee arthroplasty?

We checked intraoperative patellar tracking with both ‘towel clip technique’ and the ‘no thumb technique’ on 97 patients (167 knees) who underwent primary total knee arthroplasty to decide whether to do or not to do lateral retinacular release. Patellar tracking was assessed under pneumatic tourniquet with the no thumb technique first and re-evaluated with the towel clip technique. The tracking was graded as total contact, good contact, lateral contact and subluxation. The knees graded as total or good contact with the no thumb technique were classified into group A; those graded lateral contact or subluxation by the no thumb technique but total or good contact by the towel clip technique were classified into group B; and those graded lateral contact or subluxation by both techniques were classified into group C; in which lateral releases were performed. One hundred three, 53 and 11 knees were classified into groups A, B and C respectively. Of the 167 knees, 64 (38.3%) showed poor tracking (lateral contact or subluxation) with the no thumb technique alone. Re-evaluation of these knees with the towel clip technique significantly reduced the number with poor tracking to 11 (6.6%) knees requiring lateral retinacular release (p < 0.05). The patients were followed up for 1 year without any patella-related complications occurring. Assessment of the patellar tracking using only the no thumb technique may overestimate the need for lateral retinacular release. The use of the no thumb technique as a screening test, and re-evaluation with the towel clip technique may reduce unnecessary lateral retinacular release.