Self-denial and self-sacrifice in the life and teaching of Jesus

The sacrificial principle forms the background for the concepts of self-denial and self-sacrifice in the life and teaching of Jesus. The underlying purpose of sacrifice in the Old Testament was the offering of life to God. In accomplish¬ ing this purpose, sacrifice came to have three general aspectst gift, communion and expiation. The various forms of sacrifice were expressions of certain principles of substitution, repre¬ sentation, commutation of sacrifice, human sacrifice, and the practice of vowing persons to Yahweh.Expressions of self-denial and self-sacrifice appear in the lives of early patriarchs, but with the prophetic denunciation of improper sacrificial activity came a spiritualising of sacrificial terminology alongside the continued offering of material sacrifice. Thus language indicating concepts of self-sacrifice appears to a great extent in the Psalms; but the highest expression of self-sacrifice is found in the character of the Suffering Servant of Deutero-Issiah.The extra-canonical writings show how individual sacrifices were considered to be offerings of one's own soul. The Qumran discoveries shed light on the sacrificial cult and suggest possible contacts with the concepts of self-denial and self-sacrifice as practiced and taught by Jesus.Certain attitudes and concepts with regard to selfdenial and self-sacrifice in the life and teaching of Jesus bear the influence of Rabbinic Judaism. These include the yoke of Christ, obedience to death, the doctrine of merit, renunciation, finding greatness in service, humility and the losing of one's life to find it.In his attitude toward sacrifice, Jesus was conscious of the real value of the cultus but was quite aware of its limitations. He seems to have assumed a position of "detachment with acquiescence" in regard to the cult.The unifying element in Jesus' thoughts concerning the selX-oenial and self-sacrifice of his life is the princi¬ ple implicit in tae Old Testament sacrifices. Jesus sees ais work defined in the Suffering Servant.In this thesis a distinction is made between the Jesus of history and the kerygma of the church with regard to the Son of man sayings. The conclusion is drawn that Jesus united in his mind the three different usages of the term Son of man and employs the title in clarifying his intention of fulfiling his work of self-denial and self-sacrifice.Jesus' ethical teaching concerning self-denial and self-sacrifice demanded that the disciples understand their personal welfare to be subservient to the work of the kingdom. He taught that greatness and exaltation came through service, humility and suffering. All of this has come to be included in the terms self-denial and self-sacrifice.In the fourth Gospel there is evidence that special Son of sum words may be quite reliable for presenting the mind of Jesus. This is particularly true of John 3:14, 8:23, 12:32 and 12:34 which express belief in only the rejection and exaltation of Jesus.With regard to self-denial and self-sacrifice in the life of Jesus according to the presentation of the fourth Gospel, the author editorially declares that God gives Jesus for the world. He uses the good shepherd narrative to present the passion of Jesus as a voluntary self-sacrifice.The fourth Gospel emphasises the parallel sufferings which the disciples are to undergo. Some of the sayings may well present a tradition nearer the common original than those of the Synoptics. This seems particularly true of John 12:25, where to hate one's life is to keep it, and John 13:16, where a servant is not greater than his master. This Gospel indicates that self-denial and self-sacrifice formed a principal facet of Jesus' teachingThe thesis concludes with the Inference that there is no real distinction between the terms self-denial and self-sacrifice and that these two concepts become the unifying force which is central in Jesus* life and teaching as the means of accomplishing his purpose of offering the Kingdom of God to all

Connective tissue activation

Connective tissue activating peptide-III (CTAP-III) isolated from human platelets is a potent mitogen for human connective tissue cells in culture in addition to stimulating glycosaminoglycan synthesis, glucose consumption, and lactate formation. The amino acid composition of apparently homogeneous CTAP-III was determined, confirming the presence of two disulfide links and providing a calculated molecular weight of 11,633 daltons. Comparison of the mitogenic activity of serum and plasma-serum suggests that CTAP-III is a major mitogenic component of human serum. Seventeen strains of human connective tissue cells (synovial, cartilage, dermal and thyroid) incorporated [ 3 H]-thymidine at up to 30 times control at levels under the influence of microgram quantities of CTAP-III and caused detectable increases in thymidine incorporation at levels as low as 10–29 ng/ml. Prostaglandin E 1 (0.01 Μg/ml) and dibutyryl cyclic AMP (25 Μg/ml) potentiated the glycosaminoglycan stimulating effect of CTAP-III, but not its mitogenic effect. Cycloheximide and actinomycin D blocked the biologic actions of CTAP-III. Cortisol and penicillamine had little effect on the mitogenic activity of CTAP-III, whereas antirheumatic agents such as acetylsalicylic acid and phenylbutazone opposed the mitogenic activity when added to cultures at clinically relevant concentrations. A weak antiheparin factor secreted by platelets, low affinity platelet factor 4 (LA-PF 4 ), was shown to be similar to CTAP-III in biologic actions, electrophoretic mobility, amino acid composition, and antigenic determinants.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/37739/1/1780220308_ftp.pd

Safety and efficacy of the ChAdOx1 nCoV-19 vaccine (AZD1222) against SARS-CoV-2: an interim analysis of four randomised controlled trials in Brazil, South Africa, and the UK.

BACKGROUND: A safe and efficacious vaccine against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), if deployed with high coverage, could contribute to the control of the COVID-19 pandemic. We evaluated the safety and efficacy of the ChAdOx1 nCoV-19 vaccine in a pooled interim analysis of four trials. METHODS: This analysis includes data from four ongoing blinded, randomised, controlled trials done across the UK, Brazil, and South Africa. Participants aged 18 years and older were randomly assigned (1:1) to ChAdOx1 nCoV-19 vaccine or control (meningococcal group A, C, W, and Y conjugate vaccine or saline). Participants in the ChAdOx1 nCoV-19 group received two doses containing 5 × 1010 viral particles (standard dose; SD/SD cohort); a subset in the UK trial received a half dose as their first dose (low dose) and a standard dose as their second dose (LD/SD cohort). The primary efficacy analysis included symptomatic COVID-19 in seronegative participants with a nucleic acid amplification test-positive swab more than 14 days after a second dose of vaccine. Participants were analysed according to treatment received, with data cutoff on Nov 4, 2020. Vaccine efficacy was calculated as 1 - relative risk derived from a robust Poisson regression model adjusted for age. Studies are registered at ISRCTN89951424 and ClinicalTrials.gov, NCT04324606, NCT04400838, and NCT04444674. FINDINGS: Between April 23 and Nov 4, 2020, 23 848 participants were enrolled and 11 636 participants (7548 in the UK, 4088 in Brazil) were included in the interim primary efficacy analysis. In participants who received two standard doses, vaccine efficacy was 62·1% (95% CI 41·0-75·7; 27 [0·6%] of 4440 in the ChAdOx1 nCoV-19 group vs71 [1·6%] of 4455 in the control group) and in participants who received a low dose followed by a standard dose, efficacy was 90·0% (67·4-97·0; three [0·2%] of 1367 vs 30 [2·2%] of 1374; pinteraction=0·010). Overall vaccine efficacy across both groups was 70·4% (95·8% CI 54·8-80·6; 30 [0·5%] of 5807 vs 101 [1·7%] of 5829). From 21 days after the first dose, there were ten cases hospitalised for COVID-19, all in the control arm; two were classified as severe COVID-19, including one death. There were 74 341 person-months of safety follow-up (median 3·4 months, IQR 1·3-4·8): 175 severe adverse events occurred in 168 participants, 84 events in the ChAdOx1 nCoV-19 group and 91 in the control group. Three events were classified as possibly related to a vaccine: one in the ChAdOx1 nCoV-19 group, one in the control group, and one in a participant who remains masked to group allocation. INTERPRETATION: ChAdOx1 nCoV-19 has an acceptable safety profile and has been found to be efficacious against symptomatic COVID-19 in this interim analysis of ongoing clinical trials. FUNDING: UK Research and Innovation, National Institutes for Health Research (NIHR), Coalition for Epidemic Preparedness Innovations, Bill & Melinda Gates Foundation, Lemann Foundation, Rede D'Or, Brava and Telles Foundation, NIHR Oxford Biomedical Research Centre, Thames Valley and South Midland's NIHR Clinical Research Network, and AstraZeneca

Safety and efficacy of the ChAdOx1 nCoV-19 vaccine (AZD1222) against SARS-CoV-2: an interim analysis of four randomised controlled trials in Brazil, South Africa, and the UK

Background A safe and efficacious vaccine against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), if deployed with high coverage, could contribute to the control of the COVID-19 pandemic. We evaluated the safety and efficacy of the ChAdOx1 nCoV-19 vaccine in a pooled interim analysis of four trials. Methods This analysis includes data from four ongoing blinded, randomised, controlled trials done across the UK, Brazil, and South Africa. Participants aged 18 years and older were randomly assigned (1:1) to ChAdOx1 nCoV-19 vaccine or control (meningococcal group A, C, W, and Y conjugate vaccine or saline). Participants in the ChAdOx1 nCoV-19 group received two doses containing 5 × 1010 viral particles (standard dose; SD/SD cohort); a subset in the UK trial received a half dose as their first dose (low dose) and a standard dose as their second dose (LD/SD cohort). The primary efficacy analysis included symptomatic COVID-19 in seronegative participants with a nucleic acid amplification test-positive swab more than 14 days after a second dose of vaccine. Participants were analysed according to treatment received, with data cutoff on Nov 4, 2020. Vaccine efficacy was calculated as 1 - relative risk derived from a robust Poisson regression model adjusted for age. Studies are registered at ISRCTN89951424 and ClinicalTrials.gov, NCT04324606, NCT04400838, and NCT04444674. Findings Between April 23 and Nov 4, 2020, 23 848 participants were enrolled and 11 636 participants (7548 in the UK, 4088 in Brazil) were included in the interim primary efficacy analysis. In participants who received two standard doses, vaccine efficacy was 62·1% (95% CI 41·0–75·7; 27 [0·6%] of 4440 in the ChAdOx1 nCoV-19 group vs71 [1·6%] of 4455 in the control group) and in participants who received a low dose followed by a standard dose, efficacy was 90·0% (67·4–97·0; three [0·2%] of 1367 vs 30 [2·2%] of 1374; pinteraction=0·010). Overall vaccine efficacy across both groups was 70·4% (95·8% CI 54·8–80·6; 30 [0·5%] of 5807 vs 101 [1·7%] of 5829). From 21 days after the first dose, there were ten cases hospitalised for COVID-19, all in the control arm; two were classified as severe COVID-19, including one death. There were 74 341 person-months of safety follow-up (median 3·4 months, IQR 1·3–4·8): 175 severe adverse events occurred in 168 participants, 84 events in the ChAdOx1 nCoV-19 group and 91 in the control group. Three events were classified as possibly related to a vaccine: one in the ChAdOx1 nCoV-19 group, one in the control group, and one in a participant who remains masked to group allocation. Interpretation ChAdOx1 nCoV-19 has an acceptable safety profile and has been found to be efficacious against symptomatic COVID-19 in this interim analysis of ongoing clinical trials

Home, Colonial and Foreign: Europe, Empire and the History of Migration in 20th-century Britain

This essay reviews the increasingly rich recent literature on 20th-century transnational movements from empire and Europe to Britain and in the opposite directions, particularly on migration. It suggests that this work offers a way of thinking about British-empire and British-European relations – themes that have been comparatively neglected in 20th-century social and cultural history, especially in the period of decolonisation. While much of the literature on migration treats empire and Europe separately, as well as immigration and emigration, the essay makes connections between them, looking at changing British perceptions of Europe and the world beyond Europe: of home, colonial and foreign. It argues that the second half of the century saw an increasing erosion of distinctions between ‘colonial’ and ‘foreign’ and a reorientation of British world views towards Europe that owed little to its membership of the EU

Multicenter retrospective evaluation of transmural migration of subcutaneous ureteral bypass devices within the digestive tract in cats.

BackgroundPlacement of a subcutaneous ureteral bypass (SUB) device is an effective method to relieve all causes of ureteral obstruction in cats. Complications involving migration within the gastrointestinal tract have been seldomly described.ObjectivesTo characterize transmural migration of SUB devices within the digestive tract in cats.AnimalsEleven migrated SUB catheters identified in 8 cats between 2017 and 2021.MethodsRetrospective review of medical records of cats with a SUB device in which migration into the gastrointestinal tract was identified.ResultsThe median time from SUB device placement to implant migration was 928 days (201-2298 days). Seven cats had obstruction of the SUB device and a positive urine culture at diagnosis. The migration was identified by ultrasound in 6/11, pre-operative contrast radiography in 2/2, and only at time of surgery in 3 SUB devices. All cats underwent surgical correction. Four nephrostomy and 7 cystotomy catheters migrated. Migration occurred into the duodenum (3/11), jejunum (7/11), and colon (1/11). SUB devices were removed in 7 cats and replaced in 2 cats, with 1 cat diagnosed with 2 migration events. Gastrointestinal resection and anastomosis were performed in 7/8 cats and an enterotomy in 2 cats. Six cats survived to discharge. The median follow-up time after migration diagnosis was 365 days (range, 0-1114 days) and 2 cats are still alive.Conclusions and clinical importanceAlthough a rare complication, migration of SUB device should be considered in cats with SUB device obstruction and a positive urine culture

Ferrous iron-activatable drug conjugate achieves potent MAPK blockade in KRAS-driven tumors.

KRAS mutations drive a quarter of cancer mortality, and most are undruggable. Several inhibitors of the MAPK pathway are FDA approved but poorly tolerated at the doses needed to adequately extinguish RAS/RAF/MAPK signaling in the tumor cell. We found that oncogenic KRAS signaling induced ferrous iron (Fe2+) accumulation early in and throughout mutant KRAS-mediated transformation. We converted an FDA-approved MEK inhibitor into a ferrous iron-activatable drug conjugate (FeADC) and achieved potent MAPK blockade in tumor cells while sparing normal tissues. This innovation allowed sustainable, effective treatment of tumor-bearing animals, with tumor-selective drug activation, producing superior systemic tolerability. Ferrous iron accumulation is an exploitable feature of KRAS transformation, and FeADCs hold promise for improving the treatment of KRAS-driven solid tumors