Deconcentrating regulation in low- and middle-income country health systems: a proposed ambidextrous solution to problems with professional regulation for doctors and nurses in Kenya and Uganda.

BACKGROUND: Regulation can improve professional practice and patient care, but is often weakly implemented and enforced in health systems in low- and middle-income countries (LMICs). Taking a de-centred and frontline perspective, we examine national regulatory actors' and health professionals' views and experiences of health professional regulation in Kenya and Uganda and discuss how it might be improved in LMICs more generally. METHODS: We conducted large-scale research on professional regulation for doctors and nurses (including midwives) in Uganda and Kenya during 2019-2021. We interviewed 29 national regulatory stakeholders and 47 subnational regulatory actors, doctors, and nurses. We then ran a national survey of Kenyan and Ugandan doctors and nurses, which received 3466 responses. We thematically analysed qualitative data, conducted an exploratory factor analysis of survey data, and validated findings in four focus group discussions. RESULTS: Kenyan and Ugandan regulators were generally perceived as resource-constrained, remote, and out of touch with health professionals. This resulted in weak regulation that did little to prevent malpractice and inadequate professional education and training. However, interviewees were positive about online licencing and regulation where they had relationships with accessible regulators. Building on these positive findings, we propose an ambidextrous approach to improving regulation in LMIC health systems, which we term deconcentrating regulation. This involves developing online licencing and streamlining regulatory administration to make efficiency savings, freeing regulatory resources. These resources should then be used to develop connected subnational regulatory offices, enhance relations between regulators and health professionals, and address problems at local level. CONCLUSION: Professional regulation for doctors and nurses in Kenya and Uganda is generally perceived as weak. Yet these professionals are more positive about online licencing and regulation where they have relationships with regulators. Building on these positive findings, we propose deconcentrating regulation as a solution to regulatory problems in LMICs. However, we note resource, cultural and political barriers to its effective implementation.

Removal from the wild endangers the once widespread long-tailed macaque.

In 2022, long-tailed macaques (Macaca fascicularis), a once ubiquitous primate species, was elevated to Endangered on the International Union for Conservation of Nature (IUCN) Red List of Threatened Species. In 2023, recognizing that the long-tailed macaque is threatened by multiple factors: (1) declining native habitats across Southeast Asia; (2) overutilization for scientific, commercial, and recreational purposes; (3) inadequate regulatory mechanisms; and (4) culling due to human-macaque conflicts, a petition for rulemaking was submitted to the United States Fish and Wildlife Service to add the species to the US Endangered Species Act, the nation's most effective law to protect at risk species. The long-tailed macaque remains unprotected across much of its geographical range despite the documented continual decline of the species and related sub-species and the recent IUCN reassessment. This commentary presents a review of the factors that have contributed to the dramatic decline of this keystone species and makes a case for raising the level of protection they receive.

Surgical stress: the muscle and cognitive demands of robotic and laparoscopic surgery.

Introduction: Surgeons are among the most at-risk professionals for work-related musculoskeletal decline and experience high mental demands. This study examined the electromyographic (EMG) and electroencephalographic (EEG) activities of surgeons during surgery. Methods: Surgeons who performed live laparoscopic (LS) and robotic (RS) surgeries underwent EMG and EEG measurements. Wireless EMG was used to measure muscle activation in four muscle groups bilaterally (biceps brachii, deltoid, upper trapezius, and latissimus dorsi), and an 8-channel wireless EEG device was used to measure cognitive demand. EMG and EEG recordings were completed simultaneously during (i) noncritical bowel dissection, (ii) critical vessel dissection, and (iii) dissection after vessel control. Robust ANOVA was used to compare the %MVCRMS and alpha power between LS and RS. Results: Thirteen male surgeons performed 26 laparoscopic surgeries (LS) and 28 robotic surgeries (RS). Muscle activation was significantly higher in the right deltoid (p = 0.006), upper trapezius (left, p = 0.041; right, p = 0.032), and latissimus dorsi (left, p = 0.003; right, p = 0.014) muscles in the LS group. There was greater muscle activation in the right biceps than in the left biceps in both surgical modalities (both p = 0.0001). There was a significant effect of the time of surgery on the EEG activity (p <0.0001). A significantly greater cognitive demand was observed in the RS than in the LS with alpha, beta, theta, delta, and gamma (p = 0.002 - p <0.0001). Conclusion: These data suggest greater muscle demands in laparoscopic surgery, but greater cognitive demands in robotic surgery.

Consensus statement for perioperative care in total hip replacement and total knee replacement surgery: Enhanced Recovery After Surgery (ERAS®) Society recommendations.

Background and purpose - There is a large volume of heterogeneous studies across all Enhanced Recovery After Surgery (ERAS®) components within total hip and total knee replacement surgery. This multidisciplinary consensus review summarizes the literature, and proposes recommendations for the perioperative care of patients undergoing total hip replacement and total knee replacement with an ERAS program.Methods - Studies were selected with particular attention being paid to meta-analyses, randomized controlled trials, and large prospective cohort studies that evaluated the efficacy of individual items of the perioperative treatment pathway to expedite the achievement of discharge criteria. A consensus recommendation was reached by the group after critical appraisal of the literature.Results - This consensus statement includes 17 topic areas. Best practice includes optimizing preoperative patient education, anesthetic technique, and transfusion strategy, in combination with an opioid-sparing multimodal analgesic approach and early mobilization. There is insufficient evidence to recommend that one surgical technique (type of approach, use of a minimally invasive technique, prosthesis choice, or use of computer-assisted surgery) over another will independently effect achievement of discharge criteria.Interpretation - Based on the evidence available for each element of perioperative care pathways, the ERAS® Society presents a comprehensive consensus review, for the perioperative care of patients undergoing total hip replacement and total knee replacement surgery within an ERAS® program. This unified protocol should now be further evaluated in order to refine the protocol and verify the strength of these recommendations.

Group-specific archaeological signatures of stone tool use in wild macaques.

Stone tools in the prehistoric record are the most abundant source of evidence for understanding early hominin technological and cultural variation. The field of primate archaeology is well placed to improve our scientific knowledge by using the tool behaviours of living primates as models to test hypotheses related to the adoption of tools by early stone-age hominins. Previously we have shown that diversity in stone tool behaviour between neighbouring groups of long-tailed macaques (Macaca-fascicularis) could be explained by ecological and environmental circumstances (Luncz et al., 2017b). Here however, we report archaeological evidence, which shows that the selection and reuse of tools cannot entirely be explained by ecological diversity. These results suggest that tool-use may develop differently within species of old-world monkeys, and that the evidence of material culture can differ within the same timeframe at local geographic scales and in spite of shared environmental and ecological settings.

Antarctica and the strategic plan for biodiversity.

The Strategic Plan for Biodiversity, adopted under the auspices of the Convention on Biological Diversity, provides the basis for taking effective action to curb biodiversity loss across the planet by 2020-an urgent imperative. Yet, Antarctica and the Southern Ocean, which encompass 10% of the planet's surface, are excluded from assessments of progress against the Strategic Plan. The situation is a lost opportunity for biodiversity conservation globally. We provide such an assessment. Our evidence suggests, surprisingly, that for a region so remote and apparently pristine as the Antarctic, the biodiversity outlook is similar to that for the rest of the planet. Promisingly, however, much scope for remedial action exists.

Development of a method to measure free and bound ropivacaine in human plasma using equilibrium dialysis and hydrophilic interaction chromatography coupled to high resolution mass spectrometry.

The pharmacodynamics of absorption of local anaesthetics used during surgical procedures into tissues is governed by the amount of free drug in plasma. Toxicity may occur during continuous infusions if the levels of free drug become too high which may occur if the binding capacity of the α-1-acid glycoprotein present in plasma is exceeded. In order to monitor this a method was developed for the determination of the amount of free and bound ropivacaine in human plasma during knee and hip surgery. Rapid equilibrium dialysis units were used to separate free and bound drug then protein and buffer salts were removed by solvent precipitation. Analysis was carried out using a ZICHILIC HPLC column interfaced with an LTQ Orbitrap mass spectrometer. The following extracted ion ranges ([M+H](+)) were monitored: m/z 275.21-275.22 for ropivacaine and m/z 235.175-235.185 for lidocaine. The method was calibrated by spiking ropivacaine, and a fixed amount of lidocaine as internal standard, into plasma over the range 0.01-1.5 µg/ml. The equation of the line was y=0.886x±4.2% (n=2), forcing the curve through zero since blank plasma was free of the analyte. The values obtained for the accuracy and precision of the analysis of plasma spiked at 0.03 µg/ml and 1.5 µg/ml were 93.2%±2.8% and 95.4%±1.5% respectively (n=5). Repeat analysis of a patient sample for free and bound drug gave the following values for levels of ropivacaine: bound 1.63 µg/ml±1.48%, unbound 0.0671 µg/ml±1.68% (n=5).

The distribution and expression of CFTR restricts electrogenic anion secretion to the ileum of the brushtail possum, Trichosurus vulpecula.

In eutherian mammals, fluid secretion is essential for intestinal function. This is driven by electrogenic Cl(-) secretion, which involves a NaK2Cl cotransporter (NKCC1) in the enterocyte basolateral membrane and the cystic fibrosis transmembrane conductance regulator (CFTR) in the apical membrane. However, in the possum ileum, NKCC1 expression is low and secretagogues stimulate electrogenic HCO(3)(-) secretion driven by a basolateral NaHCO(3) cotransporter (pNBCe1). Here we investigated whether electrogenic anion secretion occurs in possum duodenum and jejunum and determined the role of CFTR in possum intestinal anion secretion. Prostaglandin E(2) (PGE(2)) and forskolin stimulated a large increase in ileal short-circuit current (I(sc)), consistent with electrogenic HCO(3)(-) secretion, but had little effect on the duodenal and jejunal I(sc). Furthermore, 5-nitro-2-(3-phenylpropylamino)benzoic acid (NPPB) and N-(2-naphthalenyl)-[(3,5-dibromo-2,4-dihydroxyphenyl)methylene]glycine hydrazide (GlyH101) inhibited cloned possum CFTR in cultured cells and the PGE(2)-stimulated ileal I(sc), implicating CFTR in ileal HCO(3)(-) secretion. Consistent with this, CFTR is expressed in the apical membrane of ileal crypt and lower villous cells, which also express pNBCe1 in the basolateral membrane. In contrast, duodenal and jejunal CFTR expression is low relative to the ileum. Jejunal pNBCe1 expression is also low, whereas duodenal and ileal pNBCe1 expression are comparable. All regions have low NKCC1 expression. These results indicate that cAMP-dependent electrogenic Cl(-) secretion does not occur in the possum small intestine because of the absence of CFTR and NKCC1. Furthermore, CFTR functions as the apical anion conductance associated with HCO(3)(-) secretion and its distribution limits electrogenic HCO(3)(-) secretion to the ileum.

A genome-wide significant linkage for severe depression on chromosome 3: the depression network study.

OBJECTIVE: The purpose of this study was to find loci for major depression via linkage analysis of a large sibling pair sample. METHOD: The authors conducted a genome-wide linkage analysis of 839 families consisting of 971 affected sibling pairs with severe recurrent major depression, comprising waves I and II of the Depression Network Study cohort. In addition to examining affected status, linkage analyses in the full data set were performed using diagnoses restricted by impairment severity, and association mapping of hits in a large case-control data set was attempted. RESULTS: The authors identified genome-wide significant linkage to chromosome 3p25-26 when the diagnoses were restricted by severity, which was a maximum LOD score of 4.0 centered at the linkage marker D3S1515. The linkage signal identified was genome-wide significant after correction for the multiple phenotypes tested, although subsequent association mapping of the region in a genome-wide association study of a U.K. depression sample did not provide significant results. CONCLUSIONS: The authors report a genome-wide significant locus for depression that implicates genes that are highly plausible for involvement in the etiology of recurrent depression. Despite the fact that association mapping in the region was negative, the linkage finding was replicated by another group who found genome-wide-significant linkage for depression in the same region. This suggests that 3p25-26 is a new locus for severe recurrent depression. This represents the first report of a genome-wide significant locus for depression that also has an independent genome-wide significant replication.

A genomewide linkage study on suicidality in major depressive disorder confirms evidence for linkage to 2p12.

Suicidal behavior is commonly associated with depression. Twin studies indicate that both suicidality and major depressive disorder (MDD) are heritable. However, epidemiological evidence suggests that the inheritance of suicidality is likely to be independent of the underlying psychiatric disorder, implying a distinct genetic contribution to suicidality. We conducted a genomewide linkage search aiming to detect genomic loci that may harbor susceptibility genes contributing to risk for suicidality in recurrent MDD. Affected sibling pair (ASP) variance components analysis was performed using the Depression Network cohort of 971 ASPs. The quantitative trait measuring suicidality as a broad phenotype, encompassing ideation and suicide attempts, was established from Schedules for Clinical Assessment in Neuropsychiatry interview items. We examined 1,060 genotyped microsatellite markers with an average spacing of 3.3 cM. Empirical thresholds for linkage evidence were set by whole-genome simulations (LOD = 2.71 for genomewide significance, 1.71 for suggestive linkage). No genomewide significant findings were found. Marker D3S1234 on 3p14 achieved suggestive linkage and yielded a maximum LOD of 1.853 (P = 0.0017), loci 9p24.3 and 18q22-q23 achieved LOD scores >1.5. We found some support for linkage to 2p12 (LOD = 1.2, P = 0.0087) which was previously implicated in linkage studies of suicidality. Our follow-up meta-analysis of five studies showed strong linkage to this region (P = 2 × 10(-6) ). In conclusion, this study analyzed suicidality as a continuous trait in MDD. We found modest evidence for linkage on 3p14. Our meta-analysis supports previous evidence of linkage to suicidality on 2p12. Some candidate genes in these regions may plausibly be implicated in suicidality. © 2010 Wiley-Liss, Inc.

Secretagogues stimulate electrogenic HCO3- secretion in the ileum of the brushtail possum, Trichosurus vulpecula: evidence for the role of a Na+/HCO3- cotransporter.

Fluid secretion is essential for intestinal function and, in eutherian mammals, is driven by electrogenic Cl(-) transport, which is dependent upon a bumetanide-sensitive, basolateral Na(+)/K(+)/2 Cl(-) cotransporter, NKCC1. However, ileal secretion in the brushtail possum, a marsupial, involves a fundamentally different process, since NKCC1 expression is low in this tissue and the secretagogue-induced short circuit current (I(sc)) is insensitive to bumetanide. In view of these differences we have investigated the basis of the secretory response of the possum ileum. In the Ussing chamber the secretory I(sc) is independent of Cl(-) but dependent upon Na(+) and serosal HCO(3)(-)/CO(2), suggesting that secretagogues stimulate electrogenic HCO(3)(-) secretion. In agreement with this, serosal DIDS (4,4'-diisothiocyano-stilbene-2,2'-disulfonate; 1 mmol l(-1)) inhibited the secretory response. However, acetazolamide (1 mmol l(-1)) and serosal amiloride (1 mmol l(-1)) had little effect, indicating that HCO(3)(-) secretion is driven by HCO(3)(-) transport from the serosal solution into the cell, rather than hydration of CO(2) by carbonic anhydrase. Consistent with this the pancreatic variant of the electrogenic Na(+)/HCO(3)(-) cotransporter (pNBC) is highly expressed in the ileal epithelium and is located in the basolateral membrane of the epithelial cells, predominantly in the mid region of the villi, with lower levels of expression in the crypts and no expression in the villous tips. We conclude that the secretory response of the possum ileum involves electrogenic HCO(3)(-) secretion driven by a basolateral pNBC and that the ileal HCO(3)(-) secretion is associated with a specialised function of the possum ileum, most probably related to hindgut fermentation.

Electrogenic Cl(-) secretion does not occur in the ileum of the Australian common brushtail possum, Trichosurus vulpecula, due to low levels of expression of the NaK2Cl cotransporter, NKCC1.

The colon of the brushtail possum does not have an electrogenic secretory response. Given the functional significance of electrogenic Cl(-) secretion in the intestine of eutherian mammals, we have investigated the secretory response in the small intestine of this marsupial. In the Ussing chamber cAMP-dependent secretagogues stimulated a sustained increase in ileal short-circuit current (Isc), whereas Ca(2+)-dependent secretagogues induced a transient increase. Both the responses were inhibited by mucosal addition of the anion channel blocker 5-nitro-2-(3-phenylpropylamino) benzoic acid (100 mciromol l(-1)), consistent with an anion secretory response. However, the responses were not inhibited by serosal bumetanide (10 mciromol l(-1)) and were independent of bath Cl(-), indicating that the stimulated ileal Isc does not involve electrogenic Cl(-) secretion driven by the NaK2Cl cotransporter, NKCC1. Consistent with this, there were low levels of NKCC1 expression in the ileal epithelium. In particular, NKCC1 expression in the ileal crypt cells was comparable to that of the villous cells. This differs from eutherian mammals where high levels of NKCC1 expression in the ileal crypt cells are associated with their role in Cl(-) secretion. The cAMP- and Ca(2+)-dependent secretory responses were inhibited by the removal of HCO(3) (-) suggesting that these responses were due to electrogenic HCO(3) (-) secretion. We conclude that the ileum of the possum does not secrete Cl(-) due to low levels of NKCC1 expression. It does however appear to secrete HCO(3) (-). These results are further significant examples of differences in the transport function of the possum intestinal epithelium compared with eutherian mammals.