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The South Pacific Gyre (SPG) plays a vital role in regulating Southern Hemisphere climate and ecosystems. The SPG has been intensifying since the twentieth century due to changes in large scale wind forcing. These changes result from variability in the Southern Annular Mode (SAM), causing warming along the eastern SPG which affects local ecosystems. However, our understanding of SPG variability on timescales greater than several decades is poor due to limited observations. Marine sediment cores are traditionally used to determine if recent ocean trends are anomalous, but rarely capture centennial variability in the southwest Pacific and limit our understanding of SPG variability. Here we capture centennial SPG dynamics using a novel high-resolution paleocirculation archive: radiocarbon reservoir ages (R) and local reservoir corrections (∆R) in SPG deep-sea black corals. We find black coral R and ∆R correlates with SAM reconstructions over 0-1000 cal BP and 2000-3000 cal BP. We propose this correlation indicates varying transport of well-ventilated subtropical waters resulting from SPG and SAM interactions. We reconstruct several 'spin up' cycles reminiscent of the recent gyre intensification, which has been attributed to anthropogenic causes. This implies gyre strength and SAM show natural co-variability on anthropogenic timescales which should factor into future climate projections., (© 2022. The Author(s).)

The leaf homogenate of Psychotria insularum is widely used in Samoan traditional medicine to treat inflammation associated with fever, body aches, swellings, wounds, elephantiasis, incontinence, skin infections, vomiting, respiratory infections, and abdominal distress. However, the bioactive components and underlying mechanisms of action are unknown. We used chemical genomic analyses in the model organism Saccharomyces cerevisiae (baker's yeast) to identify and characterize an iron homeostasis mechanism of action in the traditional medicine as an unfractionated entity to emulate its traditional use. Bioactivity-guided fractionation of the homogenate identified two flavonol glycosides, rutin and nicotiflorin, each binding iron in an ion-dependent molecular networking metabolomics analysis. Translating results to mammalian immune cells and traditional application, the iron chelator activity of the P. insularum homogenate or rutin decreased proinflammatory and enhanced anti-inflammatory cytokine responses in immune cells. Together, the synergistic power of combining traditional knowledge with chemical genomics, metabolomics, and bioassay-guided fractionation provided molecular insight into a relatively understudied Samoan traditional medicine and developed methodology to advance ethnobotany., Competing Interests: The authors declare no competing interest., (Copyright © 2021 the Author(s). Published by PNAS.)

Background: Electroconvulsive therapy (ECT) involves the induction of a seizure by the administration of an electrical stimulus via electrodes usually placed bilaterally on the scalp and was introduced as a treatment for schizophrenia in 1938. However, ECT is a controversial treatment with concerns about long-term side effects such a memory loss. Therefore, it is important to determine its clinical efficacy and safety for people with schizophrenia who are not responding to their treatment., Objectives: Our primary objective was to assess the effects (benefits and harms) of ECT for people with treatment-resistant schizophrenia.Our secondary objectives were to determine whether ECT produces a differential response in people: who are treated with unilateral compared to bilateral ECT; who have had a long (more than 12 sessions) or a short course of ECT; who are given continuation or maintenance ECT; who are diagnosed with well-defined treatment-resistant schizophrenia as opposed to less rigorously defined treatment-resistant schizophrenia (who would be expected to have a greater affective component to their illness)., Search Methods: We searched the Cochrane Schizophrenia Group's Study-Based Register of Trials including clinical trial registries on 9 September 2015 and 4 August 2017. There were no limitations on language, date, document type, or publication status for the inclusion of records in the register. We also inspected references of all the included records to identify further relevant studies., Selection Criteria: Randomised controlled trials investigating the effects of ECT in people with treatment-resistant schizophrenia., Data Collection and Analysis: Two review authors independently extracted data. For binary outcomes, we calculated the risk ratio (RR) and its 95% confidence intervals (CIs), on an intention-to-treat basis. For continuous data, we estimated the mean difference (MD) between the groups and its 95% CIs. We employed the fixed-effect model for all analyses. We assessed risk of bias for the included studies and created 'Summary of findings' tables using the GRADE framework., Main Results: We included 15 studies involving 1285 participants (1264 completers with an average age of 18 to 46 years) with treatment-resistant schizophrenia. We rated most studies (14/15, 93.3%) as at high risk of bias due to issues related to the blinding of participants and personnel. Our main outcomes of interest were: (i) clinically important response to treatment; (ii) clinically important change in cognitive functioning; (iii) leaving the study early; (iv) clinically important change in general mental state; (v) clinically important change in general functioning; (vi) number hospitalised; and (vii) death. No trial reported data on death.The included trials reported useable data for four comparisons: ECT plus standard care compared with sham-ECT added to standard care; ECT plus standard care compared with antipsychotic added to standard care; ECT plus standard care compared with standard care; and ECT alone compared with antipsychotic alone.For the comparison ECT plus standard care versus sham-ECT plus standard care, only average endpoint BPRS (Brief Psychiatric Rating Scale) scores from one study were available for mental state; no clear difference between groups was observed (short term; MD 3.60, 95% CI -3.69 to 10.89; participants = 25; studies = 1; very low-quality evidence). One study reported data for service use, measured as number readmitted; there was a clear difference favouring the ECT group (short term; RR 0.29, 95% CI 0.10 to 0.85; participants = 25; studies = 1; low-quality evidence).When ECT plus standard care was compared with antipsychotics (clozapine) plus standard care, data from one study showed no clear difference for clinically important response to treatment (medium term; RR 1.23, 95% CI 0.95 to 1.58; participants = 162; studies = 1; low-quality evidence). Clinically important change in mental state data were not available, but average endpoint BPRS scores were reported. A positive effect for the ECT group was found (short-term BPRS; MD -5.20, 95% CI -7.93 to -2.47; participants = 162; studies = 1; very low-quality evidence).When ECT plus standard care was compared with standard care, more participants in the ECT group had a clinically important response (medium term; RR 2.06, 95% CI 1.75 to 2.42; participants = 819; studies = 9; moderate-quality evidence). Data on clinically important change in cognitive functioning were not available, but data for memory deterioration were reported. Results showed that adding ECT to standard care may increase the risk of memory deterioration (short term; RR 27.00, 95% CI 1.67 to 437.68; participants = 72; studies = 1; very low-quality evidence). There were no clear differences between groups in satisfaction and acceptability of treatment, measured as leaving the study early (medium term; RR 1.18, 95% CI 0.38 to 3.63; participants = 354; studies = 3; very low-quality evidence). Only average endpoint scale scores were available for mental state (BPRS) and general functioning (Global Assessment of Functioning). There were clear differences in scores, favouring ECT group for mental state (medium term; MD -11.18, 95% CI -12.61 to -9.76; participants = 345; studies = 2; low-quality evidence) and general functioning (medium term; MD 10.66, 95% CI 6.98 to 14.34; participants = 97; studies = 2; very low-quality evidence).For the comparison ECT alone versus antipsychotics (flupenthixol) alone, only average endpoint scale scores were available for mental state and general functioning. Mental state scores were similar between groups (medium-term BPRS; MD -0.93, 95% CI -6.95 to 5.09; participants = 30; studies = 1; very low-quality evidence); general functioning scores were also similar between groups (medium-term Global Assessment of Functioning; MD -0.66, 95% CI -3.60 to 2.28; participants = 30; studies = 1; very low-quality evidence)., Authors' Conclusions: Moderate-quality evidence indicates that relative to standard care, ECT has a positive effect on medium-term clinical response for people with treatment-resistant schizophrenia. However, there is no clear and convincing advantage or disadvantage for adding ECT to standard care for other outcomes. The available evidence was also too weak to indicate whether adding ECT to standard care is superior or inferior to adding sham-ECT or other antipsychotics to standard care, and there was insufficient evidence to support or refute the use of ECT alone. More good-quality evidence is needed before firm conclusions can be made.

Antibiotics are among the most important interventions in healthcare. Resistance of bacteria to antibiotics threatens the effectiveness of treatment. Systematic reviews of antibiotic treatments often do not address resistance to antibiotics even when data are available in the original studies. This omission creates a skewed view, which emphasizes short-term efficacy and ignores the long-term consequences to the patient and other people. We offer a framework for addressing antibiotic resistance in systematic reviews. We suggest that the data on background resistance in the original trials should be reported and taken into account when interpreting results. Data on emergence of resistance (whether in the body reservoirs or in the bacteria causing infection) are important outcomes. Emergence of resistance should be taken into account when interpreting the evidence on antibiotic treatment in randomized controlled trials or systematic reviews., (© The Author 2016. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.)

Guest-love-ometer: The equilibrium inside-outside atropisomeric ratio of ortho-substituted phenyl cavitands shows a strong solvent dependence. The competition between the ortho-substituent and the solvent guest for the bowl cavity leads to a sensitive system for the measurement of relative guest binding affinities.

The goal of this study was to characterize the Yersinia pestis KIM OmpX protein. Yersinia spp. provide a model for studying several virulence processes including attachment to, and internalization by, host cells. For Yersinia enterocolitica and Yersinia pseudotuberculosis, Ail, YadA and Inv, have been implicated in these processes. In Y. pestis, YadA and Inv are inactivated. Genomic analysis of two Y. pestis strains revealed four loci with sequence homology to Ail. One of these genes, designated y1324 in the Y. pestis KIM database, encodes a protein designated OmpX. The mature protein has a predicted molecular mass of 17.47 kDa, shares approximately 70 % sequence identity with Y. enterocolitica Ail, and has an identical homologue, designated Ail, in the Y. pestis CO92 database. The present study compared the Y. pestis KIM6(+) parental strain with a mutant derivative having an engineered disruption of the OmpX structural gene. The parental strain (and a merodiploid control strain) expressed OmpX at 28 and 37 degrees C, and the protein was detectable throughout all phases of growth. OmpX was required for efficient adherence to, and internalization by, cultured HEp-2 cell monolayers and conferred resistance to the bactericidal effect of human serum. Deletion of ompX resulted in a significantly reduced autoaggregation phenotype and loss of pellicle formation in vitro. These results suggest that Y. pestis OmpX shares functional homology with Y. enterocolitica Ail in adherence, internalization into epithelial cells and serum resistance.

The design and self-assembly of six new supramolecular complexes (four triangles and two 2+2 assemblies) are described. These assemblies incorporate two new bispyridyl cavitand building blocks and were prepared in excellent yields (85-95%). The assemblies and building blocks were characterized with multinuclear NMR spectroscopy, electrospray ionization mass spectrometry, and elemental analysis. Isotopically resolved mass spectrometry along with NMR data confirms the existence of the six assemblies.

[reaction: see text] m- or p-Diiodobenzene undergoes selective double coupling reactions with arylboronic acids and esters. Selectivity for double coupling over single coupling is remarkably strong: even with a diiodobenzene:monoboronic acid ratio of 10:1, the products of double coupling are formed in good yields. Steric hindrance and electronic influences of the boronic acid or ester, and reaction conditions do not appear to impact significantly upon the outcome of the reaction. In contrast, m- and p-dibromobenzenes undergo single couplings with aryl boronic acids with high selectivity.

A survey was conducted into the use of intravascular contrast media within Scotland during 1993-4 auditing the period from April 1992 to March 1993. The first phase of the study examined the use of low osmolar contrast media and high osmolar contrast media and this obtained a 100% response rate. All users were found to adhere to Royal College of Radiologists guidelines, but as an incidental finding, only 87% recorded adverse reactions and a separate register was not always maintained. A second follow-up questionnaire was issued to examine specifically the recording of adverse reactions. A 96% response rate was obtained. Although all departments recorded adverse reactions in some form, only 13% kept a separate register. Recommendations are made that all departments should maintain a separate adverse reaction register and that there should be standardisation of the grading of reactions. Annual returns to a central body are also recommended.

We report a study on human skeletal remains excavated from a medieval city centre graveyard. The remains of approximately 75 individuals were examined and radiographs were made of selected specimens. Many bones were normal and apparently from strong, young adults. The most frequent abnormality was osteoarthritis but we also noted osteoporosis, periostitis and an example of probable Paget's disease. From measurements of long bones and using appropriate formulae, we estimated stature. The average height for males was calculated to be 172cm (5' 7") and for females 157 cm (5' 2").

Benign cystic mesothelioma of the peritoneum is a rare multicystic tumour that occurs predominantly in middle aged women with strong predilection for the surface of the pelvic viscera. Our patient was a 79-year-old woman who presented with weight loss and left upper abdominal mass showing calcification on CT. This is the first reported case of benign cystic mesothelioma with calcification. Differentiation from an adrenal tumour and peritoneal teratoma was not possible preoperatively.

Surgical plombage was used as a form of collapse therapy for pulmonary tuberculosis before the advent of reliable chemotherapy. A patient developed stridor, recurrent laryngeal nerve paralysis, and obstruction of the superior vena cava and eventually died as a result of haemorrhage into a large intrathoracic cyst, secondary to a polystan pack inserted 38 years previously.

In a retrospective study of 377 patients with bronchial carcinoma, sputum had been reported positive or suspicious for malignant cells in 59.7%. The most important factors contributing to a positive result were the histological cell type and the site of the tumour as assessed at bronchoscopy. Significantly more positive results were obtained in epidermoid tumours and those with a visible bronchoscopic abnormality. A higher proportion of positive results also occurred in large tumours, lower lobe tumours, and those associated with collapse and consolidation. The physical condition of the patient and the presence of infection in the sputum were not important factors contributing to a negative result. Although adequate numbers of sputum samples were collected the predominant problem was the large number of unsatisfactory sputum specimens. The preparation of the sputum specimens in the laboratory is important and is also a potential source of error.

Mantoux (10 tuberculin units) and tine tuberculin tests were performed in 190 subjects and the results recorded at 48, 72, and 96 hours. Altogether 1010 readings were recorded. Of these, 555 (55%) were Mantoux-test positive and 525 (52%) tine-test positive. While the tine test is marginally less sensitive, its advantages are simplicity and ease and speed of application. It thus provides a useful screening test for eliciting tuberculin sensitivity.

In view of the importance of determination of cell type in patients with bronchial carcinoma who are to be given chemotherapy a series of 140 histologically proved cases was analysed to assess the accuracy of pretreatment diagnosis by cytology and bronchial biopsy. Final histological diagnosis was made after thoracotomy (131 cases) or necropsy (9 cases). Before treatment, malignancy was diagnosed in 71% of cases with 91% accuracy in cell typing. Diagnostic yield was greatest in squamous carcinoma (81%) and least with adenocarcinoma (50%). Large-celled and small-celled anaplastic carcinomas gave yields of 61% and 68% respectively. Accuracy of cell typing was high (90-97%) except for large-celled anaplastic carcinoma (71%). All diagnostic methods were not employed in every case. In patients supplying samples the diagnosis was made by sputum cytology in 57%, by rigid bronchoscopy cytology in 57%, by fibreoptic bronchoscopy cytology in 71% and biopsy in 53%. Causes of diagnostic failures and possible means of increasing accuracy of pretreatment diagnosis were discussed.

In a controlled trial of exercise retraining in patients with severe chronic bronchitis, 33 subjects were followed for a mean period of 10.3 months. The exercise programme was supervised once a week, and daily training comprised a 12-minute walk and simple stair climbing exercises. The subjects in the exercise group showed a highly significant improvement in their walking distance, attaining a maximum increase of 24% after eight to 12 months. There was also considerable subjective improvement. The control group did not improve. No significant changes in cardiorespiratory function or muscle strength were seen. Simple exercise rehabilitation is of benefit to patients with disabling obstructive lung disease.

Bipedal lymphography and intravenous urography were carried out in 44 patients in an attempt to define the role of these procedures in the assessment of the patient with carcinoma of the bladder. Evidence of lymphatic involvement, even though unsupported by histological proof and a major abnormality on urography, conferred a worse prognosis than if these examinations were thought to be normal. Implications for therapy are considered.

Thirty patients with pulmonary complications of influenza are described, with particular emphasis on the appearance on the chest films. A wide spectrum of radiological changes was found, partly due to virus and partly to bacterial infection, both modified by the presence of other diseases.