The effect of COVID-19 on general anaesthesia rates for caesarean section. A cross-sectional analysis of six hospitals in the north-west of England.

At the onset of the global pandemic of COVID-19 (SARS-CoV-2), guidelines recommended using regional anaesthesia for caesarean section in preference to general anaesthesia. National figures from the UK suggest that 8.75% of over 170,000 caesarean sections are performed under general anaesthetic. We explored whether general anaesthesia rates for caesarean section changed during the peak of the pandemic across six maternity units in the north-west of England. We analysed anaesthetic information for 2480 caesarean sections across six maternity units from 1 April to 1 July 2020 (during the pandemic) and compared this information with data from 2555 caesarean sections performed at the same hospitals over a similar period in 2019. Primary outcome was change in general anaesthesia rate for caesarean section. Secondary outcomes included overall caesarean section rates, obstetric indications for caesarean section and regional to general anaesthesia conversion rates. A significant reduction (7.7 to 3.7%, p < 0.0001) in general anaesthetic rates, risk ratio (95%CI) 0.50 (0.39-0.93), was noted across hospitals during the pandemic. Regional to general anaesthesia conversion rates reduced (1.7 to 0.8%, p = 0.012), risk ratio (95%CI) 0.50 (0.29-0.86). Obstetric indications for caesarean sections did not change (p = 0.17) while the overall caesarean section rate increased (28.3 to 29.7%), risk ratio (95%CI) 1.02 (1.00-1.04), p = 0.052. Our analysis shows that general anaesthesia rates for caesarean section declined during the peak of the pandemic. Anaesthetic decision-making, recommendations from anaesthetic guidelines and presence of an on-site anaesthetic consultant in the delivery suite seem to be the key factors that influenced this decline.

Sensations of skin infestation linked to abnormal frontolimbic brain reactivity and differences in self-representation.

Some patients experience skin sensations of infestation and contamination that are elusive to proximate dermatological explanation. We undertook a functional magnetic resonance imaging study of the brain to demonstrate, for the first time, that central processing of infestation-relevant stimuli is altered in patients with such abnormal skin sensations. We show differences in neural activity within amygdala, insula, middle temporal lobe and frontal cortices. Patients also demonstrated altered measures of self-representation, with poorer sensitivity to internal bodily (interoceptive) signals and greater susceptibility to take on an illusion of body ownership: the rubber hand illusion. Together, these findings highlight a potential model for the maintenance of abnormal skin sensations, encompassing heightened threat processing within amygdala, increased salience of skin representations within insula and compromised prefrontal capacity for self-regulation and appraisal.

Best interests, dementia and the Mental Capacity Act (2005).

The Mental Capacity Act (2005) is an impressive piece of legislation that deserves serious ethical attention, but much of the commentary on the Act has focussed on its legal and practical implications rather than the underlying ethical concepts. This paper examines the approach that the Act takes to best interests. The Act does not provide an account of the underlying concept of best interests. Instead it lists factors that must be considered in determining best interests, and the Code of Practice to the Act states that this list is incomplete. This paper argues that this general approach is correct, contrary to some accounts of best interests. The checklist includes items that are unhelpful. Furthermore, neither the Act nor its Code of Practice provides sufficient guidance to carers faced with difficult decisions concerning best interests. This paper suggests ways in which the checklist can be developed and discusses cases that could be used in an updated Code of Practice.

Lower-crustal intrusion on the North Atlantic continental margin.

When continents break apart, the rifting is sometimes accompanied by the production of large volumes of molten rock. The total melt volume, however, is uncertain, because only part of it has erupted at the surface. Furthermore, the cause of the magmatism is still disputed-specifically, whether or not it is due to increased mantle temperatures. We recorded deep-penetration normal-incidence and wide-angle seismic profiles across the Faroe and Hatton Bank volcanic margins in the northeast Atlantic. Here we show that near the Faroe Islands, for every 1 km along strike, 360-400 km(3) of basalt is extruded, while 540-600 km(3) is intruded into the continent-ocean transition. We find that lower-crustal intrusions are focused mainly into a narrow zone approximately 50 km wide on the transition, although extruded basalts flow more than 100 km from the rift. Seismic profiles show that the melt is intruded into the lower crust as sills, which cross-cut the continental fabric, rather than as an 'underplate' of 100 per cent melt, as has often been assumed. Evidence from the measured seismic velocities and from igneous thicknesses are consistent with the dominant control on melt production being increased mantle temperatures, with no requirement for either significant active small-scale mantle convection under the rift or the presence of fertile mantle at the time of continental break-up, as has previously been suggested for the North Atlantic Ocean.

A comparison of methods used to enumerate Escherichia coli in conventionally treated sewage sludge.

AIMS: This study examined the suitability of three analytical methods for isolating and enumerating Escherichia coli from conventionally treated sewage sludge. METHODS AND RESULTS: Crude sewage, mesophilic anaerobic digested (MAD) sludge, and final product sludge samples were taken from six sewage treatment works for analysis. Two of the three methods tested were membrane filtration techniques, utilizing chromogenic E. coli/coliform (CEC) media and membrane-lactose glucuronide agar (MLGA); the third method was a most probable number (MPN) technique utilizing Colilert in Quantitray 2000 (Idexx). The methods were evaluated for variation, consistency, false-positive and false-negative results, as well as method correlation. The methods gave good and consistent recovery of E. coli for a range of conventionally treated sewage matrices. All of the methods had a false-positive rate of <3%, although MLGA had a high false-negative rate (35.5%) compared with Colilert (3.81%) and the CEC method (6.75%). This resulted in slightly lower presumptive counts but comparable numbers of confirmed counts. CONCLUSIONS: The three detection methods tested, chromogenic, MLGA and Colilert gave comparable recoveries, and did not vary by greater than one order of magnitude (1 log). SIGNIFICANCE AND IMPACT OF THE STUDY: Forthcoming revisions to the Use of Sludge in Agriculture Regulations (1989) will categorize sewage sludge as untreated, conventionally treated or enhanced treated in accordance to microbiological standards. The standard will be based upon numbers of E. coli removed through the sludge treatment process and the numbers remaining in the final product. It is recommended that the Colilert 2000 (Idexx, Westbrook, Maine) and CEC methods would be equally suitable to assess the reduction of indigenous E. coli in conventionally treated sludges, and that MLGA be used with follow-up confirmatory testing.

Lactoferrin-binding proteins of Tritrichomonas foetus.

Tritrichomonas foetus is a common, sexually transmitted, protozoan parasite of cattle. It has an essential requirement for iron, which it obtains from host lactoferrin. However, specific lactoferrin-binding protein receptors have not yet been identified in T. foetus. To differentiate specific and nonspecific binding of lactoferrin, lactoferrin affinity chromatography and Western blotting was used to identify metabolically or surface-labeled T. foetus lactoferrin-binding proteins. Bovine lactoferrin was shown to bind more efficiently than human lactoferrin, and each of these bound much better than bovine transferrin. This is relevant because T. foetus is both species-specific and only infects the mucosal surface of the reproductive tract, which has little transferrin. Whereas the majority of lactoferrin binding was specific, competitive inhibition studies showed that nonspecific, charge-related binding of lactoferrin to T. foetus may also be involved. In the presence of bovine cervical mucus, binding of lactoferrin to T. foetus was diminished, suggesting that mucus has an effect on lactoferrin binding. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis of surface biotinylated proteins affinity-purified on lactoferrin-Sepharose showed biotinylated bands at Mr values of 22, 49, 55, 72, and 155 kDa. Because lactoferrin-binding proteins may be susceptible to digestion by T. foetus extracellular cysteine proteinases, it is suspected that the 155-kDa protein is the specific lactoferrin-binding protein and that the lower-Mr lactoferrin-binding molecules may be fragmentation products that contain the lactoferrin-binding site; however, other interpretations are clearly feasible. It is possible that there may be multiple proteins or multimers of the same protein. In summary, the data showed that binding of lactoferrin to T. foetus may be regulated by an interplay of specific receptor interactions as well as by hydrophobic and charge-related interactions.

Parents' roles in shaping early adolescents' occupational aspirations.

Relations among dimensions of parenting and adolescents' occupational aspirations were examined in two specific domains: academics and sports. The sample consisted of 444 seventh graders, with approximately equal numbers of African American and European American males and females, from two-parent nondivorced families. Multiple measures were used as indicators of parents' values and behaviors, youths' values and beliefs, positive identification with parents, and adolescents' occupational aspirations. In the academic domain, parents' values predicted youths' values directly rather than indirectly through their behaviors. In contrast, fathers' behaviors mediated the relation between parents' and youths' values in the sports domain. Positive identification was directly related to adolescents' values (especially about academics); however, positive identification did not moderate the transmission of values from parent to child in either domain. Parents' values predicted adolescents' occupational aspirations via both direct and indirect pathways. Similar results were obtained for African American and European American males and females. These findings highlight the potential role of parents as socializers of achievement-related values, and, ultimately, adolescents' occupational visions of themselves in the future.

Trypanosome-derived oligopeptidase B is released into the plasma of infected rodents, where it persists and retains full catalytic activity.

A trypsin-like serine peptidase activity, levels of which correlate with blood parasitemia levels, is present in the plasma of rats acutely infected with Trypanosoma brucei brucei. Antibodies to a trypanosome peptidase with a trypsin-like substrate specificity (oligopeptidase B [OP-Tb]) cross-reacted with a protein in the plasma of trypanosome-infected rats on a Western blot. These antibodies also abolished 80% of the activity in the plasma of trypanosome-infected rats, suggesting that the activity may be attributable to a parasite-derived peptidase. We purified the enzyme responsible for the bulk of this activity from parasite-free T. b. brucei-infected rat plasma and confirmed its identity by protein sequencing. We show that live trypanosomes do not release OP-Tb in vitro and propose that disrupted parasites release it into the host circulation, where it is unregulated and retains full catalytic activity and may thus play a role in the pathogenesis of African trypanosomiasis.

Early adolescent peer orientation and adjustment during high school.

The long-term consequences of early adolescents' orientation toward peers for their adjustment during high school were assessed. Approximately 1,200 adolescents completed questionnaires in the 7th grade and in the 10th or 12th grades; course grades were also obtained from the students' school records. Early adolescents who were willing to sacrifice their talents, school performance, and parents' rules engaged in greater problem behavior and evidenced lower academic achievement than did other adolescents during high school. The poorer adjustment of adolescents with this extreme orientation toward peers was mediated by their reported involvement in deviant peer groups. In contrast, a tendency to seek advice from peers more than from parents during early adolescence had little implication for later adjustment. Discussion focuses on the need to consider the role of peer dependence along with the effects of supportive friendships during adolescence.

Characterisation of the antitrypanosomal activity of peptidyl alpha-aminoalkyl phosphonate diphenyl esters.

Two groups of irreversible serine peptidase inhibitors, peptidyl chloromethyl ketones and peptidyl phosphonate diphenyl esters, were examined for antitrypanosomal activity against the bloodstream form of Trypanosoma brucei brucei. Both peptidyl chloromethyl ketones and peptidyl phosphonate diphenyl esters inhibited trypsin-like peptidases of the parasites and exhibited antitrypanosomal activity at micromolar concentrations. In live T. b. brucei, labelled analogues of both of these groups of inhibitors primarily targeted an 80-kDa peptidase, possibly a serine oligopeptidase known as oligopeptidase B. In an in vivo mouse model of infection, one of these inhibitors, carbobenzyloxyglycyl-4-amidinophenylglycine phosphonate diphenyl ester, was curative at 5 mg kg(-1) day(-1) but appeared toxic at higher doses. There was no significant correlation between the inhibitory potency (as evaluated against purified T. b. brucei oligopeptidase B) and the in vitro antitrypanosomal efficacy of either group of inhibitors, suggesting that these inhibitors were acting on multiple targets within the parasites, or had different cell permeability properties. These findings suggest that serine peptidases may represent novel chemotherapeutic targets in African trypanosomes.

Chalcone, acyl hydrazide, and related amides kill cultured Trypanosoma brucei brucei.

BACKGROUND: Protozoan parasites of the genus Trypanosoma cause disease in a wide range of mammalian hosts. Trypanosoma brucei brucei, transmitted by tsetse fly to cattle, causes a disease (Nagana) of great economic importance in parts of Africa. T. b. brucei also serves as a model for related Trypanosoma species, which cause human sleeping sickness. MATERIALS AND METHODS: Chalcone and acyl hydrazide derivatives are known to retard the growth of Plasmodium falciparum in vitro and inhibit the malarial cysteine proteinase, falcipain. We tested the effects of these compounds on the growth of bloodstream forms of T. b. brucei in cell culture and in a murine trypanosomiasis model, and investigated their ability to inhibit trypanopain-Tb, the major cysteine proteinase of T. b. brucei. RESULTS: Several related chalcones, acyl hydrazides, and amides killed cultured bloodstream forms of T. b. brucei, with the most effective compound reducing parasite numbers by 50% relative to control populations at a concentration of 240 nM. The most effective inhibitors protected mice from an otherwise lethal T. b. brucei infection in an in vivo model of acute parasite infection. Many of the compounds also inhibited trypanopain-Tb, with the most effective inhibitor having a Ki value of 27 nM. Ki values for trypanopain-Tb inhibition were up to 50- to 100-fold lower than for inhibition of mammalian cathepsin L, suggesting the possibility of selective inhibition of the parasite enzyme. CONCLUSIONS: Chalcones, acyl hydrazides, and amides show promise as antitrypanosomal chemotherapeutic agents, with trypanopain-Tb possibly being one of their in vivo targets.

Do self-fulfilling prophecies accumulate, dissipate, or remain stable over time?

The authors examined whether self-fulfilling prophecies accumulate, dissipate, or remain stable over time by using data from more than 500 6th- through 12th-grade students in public school math classes. The authors used multiple regression analyses to assess the extent to which teacher perceptions predicted students' final math marks and standardized math-test scores from 6th through 12th grade. Control variables included 5 measures of student motivation and 2 measures of previous achievement. The results were consistent with both the dissipation and stability hypotheses. Implications for understanding the extent to which social perception creates social reality and the role of expectations in social problems are discussed.

Oligopeptidase B from Trypanosoma brucei, a new member of an emerging subgroup of serine oligopeptidases.

Trypanosoma brucei contains a soluble serine oligopeptidase (OP-Tb) that is released into the host bloodstream during infection, where it has been postulated to participate in the pathogenesis of African trypanosomiasis. Here, we report the identification of a single copy gene encoding the T. brucei oligopeptidase and a homologue from the related trypanosomatid pathogen Leishmania major. The enzymes encoded by these genes belong to an emerging subgroup of the prolyl oligopeptidase family of serine hydrolases, referred to as oligopeptidase B. The trypanosomatid oligopeptidases share 70% amino acid sequence identity with oligopeptidase B from the intracellular pathogen Trypanosoma cruzi, which has a demonstrated role in mammalian host cell signaling and invasion. OP-Tb exhibited no activity toward the prolyl oligopeptidase substrate H-Gly-Pro-7-amido-4-methylcoumarin. Instead, it had activity toward substrates of trypsin-like enzymes, particularly those that have basic amino acids in both P(1) and P(2) (e.g. benzyloxycarbonyl-Arg-Arg-7-amido-4-methylcoumarin k(cat)/K(m) = 529 s(-1) microM(-1)). The activity of OP-Tb was enhanced by reducing agents and by polyamines, suggesting that these agents may act as in vivo regulators of OP-Tb activity. This study provides the basis of the characterization of a novel subgroup of serine oligopeptidases from kinetoplastid protozoa with potential roles in pathogenesis.

Purification and characterisation of a trypsin-like serine oligopeptidase from Trypanosoma congolense.

Trypanosoma brucei contain a serine oligopeptidase (OP-Tb) that is released into (and remains active in) the blood of trypanosome-infected animals. Here a similar enzyme from Trypanosoma congolense is described. This oligopeptidase, called OP-Tc, was purified using three-phase partitioning, and ion-exchange and affinity chromatography. OP-Tc is inhibited by alkylating agents, by serine peptidase-specific inhibitors including 3,4-dichloroisocoumarin, 4-(2-aminoethyl)benzenesulfonylfluoride and diispropylfluoro-phosphate and by other peptidase inhibitors including leupeptin, antipain and peptidyl chloromethyl ketones. Reducing agents such as dithiothreitol enhanced activity as did heparin, spermine and spermidine. The enzyme has trypsin-like specificity since it cleaved fluorogenic peptides that have basic amino acid residues (Arg or Lys) in the P1 position. Potential substrates without a basic residue in P1 were not hydrolysed. Although OP-Tc has weak arginine aminopeptidase activity, the enzyme clearly preferred substrates that had amino acids in the P2 and P3 positions. Overall, OP-Tc appears to be less efficient than OP-Tb because it usually displayed lower k(cat)/Km values for the substrates tested. However, like OP-Tb, the best substrate for OP-Tc was Cbz-Arg-Arg-AMC (Km = 0.72 microM, k(cat) = 96 s(-1)). OP-Tc preference for amino acids in the P2 position was (Gly,Lys,Arg) > Phe > Leu > Pro. The results also suggest that the P3-binding site has hydrophobic characteristics. OP-Tc may not be a naturally immunodominant molecule because neither IgG nor IgM anti- OP-Tc antibodies were detected in the blood of experimentally infected cattle.

Cysteine proteinase inhibitors kill cultured bloodstream forms of Trypanosoma brucei brucei.

Trypanosoma brucei brucei is a causative agent of bovine trypanosomiasis (nagana), a disease of considerable economic significance in much of Africa. Here we report investigations on the effects of various irreversible cysteine proteinase inhibitors, including vinyl sulfones (VS), peptidyl chloromethylketones (CMK), diazomethylketones, and fluoromethyl ketones, on the major lysosomal cysteine proteinase (trypanopain-Tb) of T. b. brucei and on in vitro-cultured bloodstream forms of the parasite. Many of the tested inhibitors were trypanocidal at low micromolar concentrations. Methylpiperazine urea-Phe-homoPhe-VS was the most effective trypanocidal agent, killing 50% of test populations at a work ing concentration of 0.11 microM, while carbobenzoxy-Phe-Phe-CMK was the most trypanocidal of the methylketones with an IC50 of 3.6 microM. Labelling of live and lysed T. b. brucei with biotinylated inhibitor derivatives suggests that trypanopain-Tb is the likely intracellular target for these inhibitors. Kinetic analysis of the inhibition of purified trypanopain-Tb by the inhibitors showed that most had kass values in the 10(6) M-1 s-1 range. We conclude that cysteine proteinase inhibitors have potential as trypanocidal agents and that a major target of these compounds is the lysosomal enzyme trypanopain-Tb.

Financial strain, parenting behaviors, and adolescents' achievement: testing model equivalence between African American and European American single- and two-parent families.

This study tested the equivalence of a theoretical model of parenting behaviors linking financial strain to adolescents' achievement for African American and European American families and for single- and two-parent families. The sample included an economic cross-section of African American (n = 387) and European American families (n = 230) from single- (n = 171) and two-parent (n = 446) homes. Multi-group analyses revealed no significant differences in the structural equation models between the African American and European American families, or between the single- and two-parent families. Results demonstrated that negative parent-adolescent relationships and parental school involvement mediated the relation between financial strain and adolescents' academic achievement.

The development of children ages 6 to 14.

The years between 6 and 14--middle childhood and early adolescence--are a time of important developmental advances that establish children's sense of identity. During these years, children make strides toward adulthood by becoming competent, independent, self-aware, and involved in the world beyond their families. Biological and cognitive changes transform children's bodies and minds. Social relationships and roles change dramatically as children enter school, join programs, and become involved with peers and adults outside their families. During middle childhood, children develop a sense of self-esteem and individuality, comparing themselves with their peers. They come to expect they will succeed or fail at different tasks. They may develop an orientation toward achievement that will color their response to school and other challenges for many years. In early adolescence, the tumultuous physical and social changes that accompany puberty, the desire for autonomy and distance from the family, and the transition from elementary school to middle school or junior high can all cause problems for young people. When adolescents are in settings (in school, at home, or in community programs) that are not attuned to their needs and emerging independence, they can lose confidence in themselves and slip into negative behavior patterns such as truancy and school dropout. This article examines the developmental changes that characterize the years from 6 to 14, and it highlights ways in which the organization of programs, schools, and family life can better support positive outcomes for youths.