Blood-stage malaria vaccine candidate RH5.1/Matrix-M in healthy Tanzanian adults and children; an open-label, non-randomised, first-in-human, single-centre, phase 1b trial.

BACKGROUND: A blood-stage Plasmodium falciparum malaria vaccine would provide a second line of defence to complement partially effective or waning immunity conferred by the approved pre-erythrocytic vaccines. RH5.1 is a soluble protein vaccine candidate for blood-stage P falciparum, formulated with Matrix-M adjuvant to assess safety and immunogenicity in a malaria-endemic adult and paediatric population for the first time. METHODS: We did a non-randomised, phase 1b, single-centre, dose-escalation, age de-escalation, first-in-human trial of RH5.1/Matrix-M in Bagamoyo, Tanzania. We recruited healthy adults (aged 18-45 years) and children (aged 5-17 months) to receive the RH5.1/Matrix-M vaccine candidate in the following three-dose regimens: 10 µg RH5.1 at 0, 1, and 2 months (Adults 10M), and the higher dose of 50 µg RH5.1 at 0 and 1 month and 10 µg RH5.1 at 6 months (delayed-fractional third dose regimen; Adults DFx). Children received either 10 µg RH5.1 at 0, 1, and 2 months (Children 10M) or 10 µg RH5.1 at 0, 1, and 6 months (delayed third dose regimen; Children 10D), and were recruited in parallel, followed by children who received the dose-escalation regimen (Children DFx) and children with higher malaria pre-exposure who also received the dose-escalation regimen (High Children DFx). All RH5.1 doses were formulated with 50 µg Matrix-M adjuvant. Primary outcomes for vaccine safety were solicited and unsolicited adverse events after each vaccination, along with any serious adverse events during the study period. The secondary outcome measures for immunogenicity were the concentration and avidity of anti-RH5.1 serum IgG antibodies and their percentage growth inhibition activity (GIA) in vitro, as well as cellular immunogenicity to RH5.1. All participants receiving at least one dose of vaccine were included in the primary analyses. This trial is registered at ClinicalTrials.gov, NCT04318002, and is now complete. FINDINGS: Between Jan 25, 2021, and April 15, 2021, we recruited 12 adults (six [50%] in the Adults 10M group and six [50%] in the Adults DFx group) and 48 children (12 each in the Children 10M, Children 10D, Children DFx, and High Children DFx groups). 57 (95%) of 60 participants completed the vaccination series and 55 (92%) completed 22 months of follow-up following the third vaccination. Vaccinations were well-tolerated across both age groups. There were five serious adverse events involving four child participants during the trial, none of which were deemed related to vaccination. RH5-specific T cell and serum IgG antibody responses were induced by vaccination and purified total IgG showed in vitro GIA against P falciparum. We found similar functional quality (ie, GIA per µg RH5-specific IgG) across all age groups and dosing regimens at 14 days after the final vaccination; the concentration of RH5.1-specific polyclonal IgG required to give 50% GIA was 14·3 µg/mL (95% CI 13·4-15·2). 11 children were vaccinated with the delayed third dose regimen and showed the highest median anti-RH5 serum IgG concentration 14 days following the third vaccination (723 µg/mL [IQR 511-1000]), resulting in all 11 who received the full series showing greater than 60% GIA following dilution of total IgG to 2·5 mg/mL (median 88% [IQR 81-94]). INTERPRETATION: The RH5.1/Matrix-M vaccine candidate shows an acceptable safety and reactogenicity profile in both adults and 5-17-month-old children residing in a malaria-endemic area, with all children in the delayed third dose regimen reaching a level of GIA previously associated with protective outcome against blood-stage P falciparum challenge in non-human primates. These data support onward efficacy assessment of this vaccine candidate against clinical malaria in young African children. FUNDING: The European and Developing Countries Clinical Trials Partnership; the UK Medical Research Council; the UK Department for International Development; the National Institute for Health and Care Research Oxford Biomedical Research Centre; the Division of Intramural Research, National Institute of Allergy and Infectious Diseases; the US Agency for International Development; and the Wellcome Trust.

Oral Structural Dysphagia in Children.

Oral causes of dysphagia in infancy may involve the lips, the tongue, or the palate. Whereas ankyloglossia is commonly diagnosed in infants with dysphagia, assessment of the need for surgical intervention may be less straightforward. Tongue size (macroglossia) may be associated with dysphagia as it may cause limitation of movement of the food or milk bolus by the lips or cheeks. Congenital conditions such as cleft lip and palate, micrognathia, or craniofacial microsomia may also be associated with dysphagia. Diagnosis and treatment of these conditions can be improved with the engagement of lactation and feeding experts as well as multidisciplinary craniofacial teams.

Antioxidants green tea extract and nordihydroguaiaretic acid confer species and strain-specific lifespan and health effects in Caenorhabditis nematodes.

The Caenorhabditis Intervention Testing Program (CITP) is an NIH-funded research consortium of investigators who conduct analyses at three independent sites to identify chemical interventions that reproducibly promote health and lifespan in a robust manner. The founding principle of the CITP is that compounds with positive effects across a genetically diverse panel of Caenorhabditis species and strains are likely engaging conserved biochemical pathways to exert their effects. As such, interventions that are broadly efficacious might be considered prominent compounds for translation for pre-clinical research and human clinical applications. Here, we report results generated using a recently streamlined pipeline approach for the evaluation of the effects of chemical compounds on lifespan and health. We studied five compounds previously shown to extend C. elegans lifespan or thought to promote mammalian health: 17α-estradiol, acarbose, green tea extract, nordihydroguaiaretic acid, and rapamycin. We found that green tea extract and nordihydroguaiaretic acid extend Caenorhabditis lifespan in a species-specific manner. Additionally, these two antioxidants conferred assay-specific effects in some studies-for example, decreasing survival for certain genetic backgrounds in manual survival assays in contrast with extended lifespan as assayed using automated C. elegans Lifespan Machines. We also observed that GTE and NDGA impact on older adult mobility capacity is dependent on genetic background, and that GTE reduces oxidative stress resistance in some Caenorhabditis strains. Overall, our analysis of the five compounds supports the general idea that genetic background and assay type can influence lifespan and health effects of compounds, and underscores that lifespan and health can be uncoupled by chemical interventions.

Toxicokinetics of a humanized anti-cocaine monoclonal antibody in male and female rats and lack of cross-reactivity.

A humanized monoclonal antibody h2E2 designed to bind cocaine with high affinity, specificity, and a long half-life (~7 d in rats) is being developed as a treatment for cocaine use disorder. We report here a pharmacokinetic (PK) study of h2E2 using male and female rats conducted under a Good Laboratory Practice (GLP) protocol over a dose range of 40 to 1200 mg/kg. The maximum concentration measured in rat plasma (Cmax) varied proportionately to the dose administered in both male and female rats. The terminal elimination half-lives (t1/2ß) were not significantly different in male and female rats at all doses tested. Importantly, this study reports pharmacokinetics for a humanized monoclonal antibody at a dose never tested before. h2E2 has a high affinity for cocaine, whereas low or no affinity was demonstrated for cocaine metabolites (all except cocaethylene), endogenous monoamines, and methamphetamine. This demonstrates its specificity and a potential lack of interactions with physiological and endocrine systems. A review of the clinical signs in single-dose toxicity studies in rats revealed no effects on the central nervous, respiratory, or cardiovascular systems following single intravenous doses of 40 to 1200 mg/kg. This study predicts that this monoclonal antibody may be safe and effective in humans.

C-Terminal Arginine-Selective Cleavage of Peptides as a Method for Mimicking Carboxypeptidase B.

C-Terminal residues play a pivotal role in dictating the structure and functions of proteins. Herein, we report a mild, efficient, chemoselective, and site-selective chemical method that allows for precise chemical proteolysis at C-terminal arginine dictated by 9,10-phenanthrenequinone independent of the remaining sequence. This biomimetic approach also exhibits the potential to synthesize C-terminal methyl ester (-CO2Me) peptides.

Apolipoprotein B-100-mediated motor neuron degeneration in sporadic amyotrophic lateral sclerosis.

Amyotrophic lateral sclerosis is a fatal neurodegenerative disease characterized by motor neuron degeneration. Approximately 90% of cases occur sporadically with no known cause while 10% are familial cases arising from known inherited genetic mutations. In vivo studies have predominantly utilized transgenic models harbouring amyotrophic lateral sclerosis-associated gene mutations, which have not hitherto elucidated mechanisms underlying motor neuron death or identified therapeutic targets specific to sporadic amyotrophic lateral sclerosis. Here we provide evidence demonstrating pathogenic differences in CSF from patients with sporadic amyotrophic lateral sclerosis and familial amyotrophic lateral sclerosis patients with mutations in SOD1, C9orf72 and TARDBP. Using a novel CSF-mediated animal model, we show that intrathecal delivery of sporadic amyotrophic lateral sclerosis patient-derived CSF into the cervical subarachnoid space in adult wild-type mice induces permanent motor disability which is associated with hallmark pathological features of amyotrophic lateral sclerosis including motor neuron loss, cytoplasmic TDP-43 translocation, reactive astrogliosis and microglial activation. Motor impairments are not induced by SOD1, C9orf72 or TARDBP CSF, although a moderate degree of histopathological change occurs in C9orf72 and TARDBP CSF-injected mice. By conducting a series of CSF filtration studies and global proteomic analysis of CSF, we identified apolipoprotein B-100 in sporadic amyotrophic lateral sclerosis CSF as the putative agent responsible for inducing motor disability, motor neuron degeneration and pathological translocation of TDP-43. Apolipoprotein B-100 alone is sufficient to recapitulate clinical and pathological outcomes in vivo and induce death of human induced pluripotent stem cell-derived motor neurons in vitro. Targeted removal of apolipoprotein B-100 from sporadic amyotrophic lateral sclerosis CSF via filtration or immunodepletion successfully attenuated the neurotoxic capacity of sporadic amyotrophic lateral sclerosis CSF to induce motor disability, motor neuron death, and TDP-43 translocation. This study presents apolipoprotein B-100 as a novel therapeutic target specific for the predominant sporadic form of amyotrophic lateral sclerosis and establishes proof-of-concept to support CSF pheresis as a therapeutic strategy for mitigating neurotoxicity in sporadic amyotrophic lateral sclerosis.

Paediatric admissions to a TB hospital: reasons for admission, clinical profile and outcomes.

BACKGROUND: Brooklyn Chest Hospital (BCH) is a specialised TB hospital in Cape Town, South Africa. We describe reasons for admission, patient profiles and hospital-discharge outcomes in children admitted to BCH. This was compared to a previous study (2000-2001).METHODS: This retrospective, descriptive study included all children (0-14 years) admitted to BCH from January 2016 to December 2017. Data collected from patient folders and a laboratory database included demographic data, reasons for admission, clinical data and hospital outcomes.RESULTS: Of 263 children admitted, 133 (50.6%) were male. The median age was 32 months (IQR 15-75); 48 (18.3%) were HIV-positive and 150 (57.0%) had bacteriologically confirmed TB. Reasons for admission included social/caregiver-related (n = 119, 45.2%), drug-resistant TB (n = 114, 43.3%), TB meningitis (n = 86, 32.7%) and other severe types of TB (n = 63, 24.0%); 110 (41.8%) children had >1 reason for admission. TB meningitis admissions decreased (P = 0.014) and those for drug-resistant TB increased (P < 0.001) compared to 2000-2001. Pulmonary TB was diagnosed in 234 (89.0%), extrapulmonary TB in 149 (56.7%) and 126 (47.9%) had both. At discharge, 73 (27.8%) had completed treatment, 182 (69.2%) were transferred out to complete treatment at community clinics, and 6 (2.3%) died.CONCLUSIONS: Although most children were admitted for clinical reasons, social/caregiver-related reasons were also important.

Comparison of two-year treatment outcomes between subthreshold micropulse (577 nm) laser and aflibercept for diabetic macular edema.

PURPOSE: To compare two-year treatment outcomes of subthreshold micropulse (577 nm) laser and aflibercept for diabetic macular edema (DME). STUDY DESIGN: Retrospective case-control study. METHODS: A total 164 eyes in 164 DME patients treated with either micropulse laser (86 eyes) or intravitreal aflibercept monotherapy (78 eyes) were recruited. Main outcome measures included at least five Early Treatment Diabetic Retinopathy Study (ETDRS) letters' improvement from baseline at 6, 12 and 24 months. RESULTS: Rescue aflibercept was initiated in 24% of eyes in micropulse laser group. At 6-month visit the aflibercept group achieved a higher percentage of eyes with at least 5-letter visual acuity improvement than micropulse laser group (56% vs 38%, P = 0.044), however, this was not the case at 12-month (45% vs 49%, P = 0.584) and 24-month visits (49% vs 57%, P = 0.227). At 6-month visit the aflibercept group achieved a higher percentage of eyes with at least 10% improvement of central macular thickness (73% vs 49%, P = 0.005), but this was not the case at 12-month (73% vs 70%, P = 0.995) and 24-month visits (85% vs 84%, P = 0.872). CONCLUSION: Aflibercept achieved faster and higher rates of anatomical and functional improvement than micropulse laser in DME patients. Long term efficacy of treatment did not result in significant differences between aflibercept monotherapy and micropulse laser in DME patients. Primary treatment of micropulse laser with deferred rescue aflibercept might be the treatment option without reducing the chance of visual improvement in DME eyes.

Proliferating pilomatricoma in a 9-year-old girl.

Proliferating pilomatricoma is a rare, benign tumor of hair matrix origin that rarely occurs in children. We report the case of a 9-year-old girl with a rapidly growing, proliferating pilomatricoma located on the glabella. The lesion was embolized and surgically excised, with histopathological examination of the tissue confirming the diagnosis of proliferating pilomatricoma.

Exophytic Lumbar Vertebral Body Mass in an Adult with Back Pain.

Chordomas are rare primary bone malignancies derived from notochord remnants. The tumors often are slow-growing and often present with indolent, nonspecific symptoms. Nevertheless, chordomas are locally aggressive and highly prone to local recurrence, necessitating precise planning before biopsy and/or surgical resection. Familiarity with the imaging features of chordomas is, therefore, essential. This case highlights the typical imaging and pathologic features of a spinal chordoma as well as the surgical approach and the patient's subsequent outcome.

Discovery of a Chiral DNA-Targeted Platinum-Acridine Agent with Potent Enantioselective Anticancer Activity.

A structure-activity relationship study was performed for a set of rigidified platinum-acridine anticancer agents containing linkers derived from chiral pyrrolidine and piperidine scaffolds. Screening a library of microscale reactions and selected resynthesized compounds in non-small-cell lung cancer (NSCLC) cells showed that cytotoxicities varied by more than three orders of magnitude. A potent hit compound was discovered containing a (R)-N-(piperidin-3-yl) linker (P2-6R), which killed NCI-H460 and A549 lung cancer cells 100 times more effectively than the S enantiomer (P2-6S). P2-6R accumulated in A549 cells significantly faster and produced 50-fold higher DNA adduct levels than P2-6S. Ligand similarity analysis suggests that only module 6R may be compatible with strainless monofunctional intercalative binding. NCI-60 screening and COMPARE analysis highlights the spectrum of activity and potential utility of P2-6R for treating NSCLC and other solid tumors.

Tracheal tube size in adults undergoing elective surgery - a narrative review.

Tracheal tubes are routinely used in adults undergoing elective surgery. The size of the tracheal tube, defined by its internal diameter, is often generically selected according to sex, with 7-7.5 mm and 8-8.5 mm tubes recommended in women and men, respectively. Tracheal diameter in adults is highly variable, being narrowest at the subglottis, and is affected by height and sex. The outer diameter of routinely used tracheal tubes may exceed these dimensions, traumatise the airway and increase the risk of postoperative sore throat and hoarseness. These complications disproportionately affect women and may be mitigated by using smaller tracheal tubes (6-6.5 mm). Patient safety concerns about using small tracheal tubes are based on critical care populations undergoing prolonged periods of tracheal intubation and not patients undergoing elective surgery. The internal diameter of the tube corresponds to its clinical utility. Tracheal tubes as small as 6.0 mm will accommodate routinely used intubation aids, suction devices and slim-line fibreoptic bronchoscopes. Positive pressure ventilation may be performed without increasing the risk of ventilator-induced lung injury or air trapping, even when high minute volumes are required. There is also no demonstrable increased risk of aspiration or cuff pressure damage when using smaller tracheal tubes. Small tracheal tubes may not be safe in all patients, such as those with high secretion loads and airflow limitation. A balanced view of risks and benefits should be taken appropriate to the clinical context, to select the smallest tracheal tube that permits safe peri-operative management.

A novel approach for eliciting adolescent MDR-TB treatment tolerability: qualitative data from South Africa.

SETTING: Treatment tolerability among adolescents diagnosed with multidrug-resistant tuberculosis (MDR-TB) is underexplored. We present qualitative study data from adolescents participating in an observational cohort in the Western Cape, South Africa.OBJECTIVE: To elicit adolescent experiences of MDR-TB diagnosis and treatment with qualitative body-mapping activities and discussions.DESIGN: Adolescents in an observational MDR-TB cohort received routine toxicity and audiology screenings from clinicians. We enrolled eight participants (age 10-16 years) to participate in additional body-mapping activities and in-depth interviews. A thematic deductive analysis was conducted. We present a comparison of the clinical assessments and qualitative discussions.RESULTS: Adolescent participants reported few adverse effects on standard toxicity and audiology reports. Only nausea and vomiting were reported in >10% of cases, all of which were grade 1 (causing no/minimal interference) adverse effects (AEs). However, when comparing toxicity reports with qualitative body-mapping activities and interviews, we found previously unreported AEs (neurosensory alteration, neuromuscular weakness, pain); underestimated severity of AEs (nausea, itching); and missed psychosocial symptoms (signs of depression).CONCLUSION: Adolescents receiving treatment for MDR-TB experienced treatment-related AEs that were not reported during routine clinical assessments. Psychosocial experiences of adolescents are not taken into account. More research is needed to understand the experiences of this vulnerable group. We recommend that drug safety monitoring be adapted to include more creative and patient-driven reporting mechanisms for vulnerable groups, including children.

Analgesic benefits and clinical role of the posterior suprascapular nerve block in shoulder surgery: a systematic review, meta-analysis and trial sequential analysis.

The posterior suprascapular nerve block has been proposed as an analgesic alternative for shoulder surgery based on the publication of several comparisons with interscalene block that failed to detect differences in analgesic outcomes. However, quantification of the absolute treatment effect of suprascapular nerve block on its own, in comparison with no block (control), to corroborate the aforementioned conclusions has been lacking. This study examines the absolute analgesic efficacy of suprascapular nerve block compared with control for shoulder surgery. We systematically sought electronic databases for studies comparing suprascapular nerve block with control. The primary outcomes included postoperative 24-h cumulative oral morphine consumption and the difference in area under the curve for 24-h pooled pain scores. Secondary outcomes included the incidence of opioid-related side-effects (postoperative nausea and vomiting) and patient satisfaction. Data were pooled using random-effects modelling. Ten studies (700 patients) were analysed; all studies examined landmark-guided posterior suprascapular nerve block performed in the suprascapular fossa. Suprascapular nerve block was statistically but not clinically superior to control for postoperative 24-h cumulative oral morphine consumption, with a weighted mean difference (99%CI) of 11.41 mg (-21.28 to -1.54; p = 0.003). Suprascapular nerve block was also statistically but not clinically superior to control for area under the curve of pain scores, with a mean difference of 1.01 cm.h. Nonetheless, suprascapular nerve block reduced the odds of postoperative nausea and vomiting and improved patient satisfaction. This review suggests that the landmark-guided posterior suprascapular nerve block does not provide clinically important analgesic benefits for shoulder surgery. Investigation of other interscalene block alternatives is warranted.

Distribution pattern and multivariate analyses for anthropogenic apportionment of selected coastal water in Macajalar Bay, Philippines.

Macajalar Bay in the southern Philippines has become an attractive thoroughfare with recent developments, rendering anthropogenic input to the coastal waters. Expediting coastal resource management strategies necessitates the present study on coastal water characteristics. This was aided with distribution pattern and multivariate analyses for apportioning possible anthropogenic inputs. A total of 15 biophysicochemical characteristics were studied covering two municipalities (Opol and Jasaan) with six subcoastal communities in 2017. Data were all processed for Q test to eliminate outliers before distribution analyses using univariate (descriptive), inferential (t test, one-way ANOVA, Pearson correlation), and multivariate statistics (hierarchal cluster analysis (HCA) and principal component analysis (PCA)). Overall, higher concentrations were determined in the ecotourism site (Opol) than in the industrial site (Jasaan) as sampling months progressed except for oil and grease. Results for total coliform, fecal coliform, heterotrophic plate count (HPC), total suspended solids (TSS), chemical oxygen demand (COD), and oil and grease regardless of spatial-temporal variations exceeded the standards. Distribution pattern revealed variations selectively for pH, temperature, dissolved oxygen (DO), and oil and grease, indicating site-specific distribution. HCA and PCA results corroborated correlation matrices showing elevated concentrations in an ecotourism site (Opol) apportioned anthropogenic input mainly due to rural development and ecotourism. Likewise, in the industrial site (Jasaan), HCA and PCA results reflected possible anthropogenic input from rural development and industries. Overall, anthropogenic apportionment in the bay was influenced by rural development, ecotourism, and industries.

Impact of Sequential Opioid Dose Reduction Interventions in a State Medicaid Program Between 2002 and 2017.

Policies that address opioid dose limits may help to decrease high-risk opioid prescribing. We evaluated 3 sequential and progressive decreases in high-dose (HD) opioid limits implemented by Massachusetts Medicaid over 15 years. The study population included members ages 18 to 64 years with ≥1 claim for a schedule II opioid between January 2002 and March 2017. The 3 interventions consisted of prior authorization requirements for prescriptions exceeding the morphine equivalent dose (MED) HD dose limits: >360 mg (intervention 1a and 1b), >240 mg (intervention 2), and >120 mg (intervention 3). A segmented regression evaluated the change in natural log of the average daily MED (AD_MED). The natural log of the AD_MED decreased during the 6 quarters after intervention 1a (P < .001), immediately after intervention 1b (P = .0002), and continued to decrease over the following 8 quarters (P = .023). The natural log of the AD_MED decreased immediately after intervention 2 (P = .002) and again after intervention 3 (P < .001). The percentage of users exceeding the HD limits of 360 mg, 240 mg, and 120 mg MED decreased by 87.3%, 79.8%, and 75.2% from baseline, respectively. The natural log of the AD_MED decreased among members after implementation of 3 sequential and progressive HD prior authorization limits, as did the percentage of members exceeding each of the HD limits. PERSPECTIVE: This study demonstrates the longitudinal impact of a prior authorization policy-based HD limit in a Medicaid population. This study contributes to options for policymakers and other Medicaid programs as a potential strategy to assist in addressing the opioid epidemic.

Midpoint transverse process to pleura catheter placement for postoperative analgesia following video-assisted thoracoscopic surgery.

The ultrasound-guided midpoint transverse process to pleura block has been described as an alternative end-point for thoracic paravertebral blockade. Although originally described as a single-level block, midpoint transverse process to pleura blockade may cover more than one level when larger volumes of injectate are used. Moreover, a continuous catheter midpoint transverse process to pleura blockade technique was previously thought to be unfeasible. We report three cases where a midpoint transverse process to pleura continuous catheter technique was successfully used for postoperative analgesia following video-assisted thoracoscopic surgery.

Marine plastics threaten giant Atlantic Marine Protected Areas.

There has been a recent shift in global perception of plastics in the environment, resulting in a call for greater action. Science and the popular media have highlighted plastic as an increasing stressor [1,2]. Efforts have been made to confer protected status to some remote locations, forming some of the world's largest Marine Protected Areas, including several UK overseas territories. We assessed plastic at these remote Atlantic Marine Protected Areas, surveying the shore, sea surface, water column and seabed, and found drastic changes from 2013-2018. Working from the RRS James Clark Ross at Ascension, St. Helena, Tristan da Cunha, Gough and the Falkland Islands (Figure 1A), we showed that marine debris on beaches has increased more than 10 fold in the past decade. Sea surface plastics have also increased, with in-water plastics occurring at densities of 0.1 items m-3; plastics on seabeds were observed at ≤ 0.01 items m-2. For the first time, beach densities of plastics at remote South Atlantic sites approached those at industrialised North Atlantic sites. This increase even occurs hundreds of meters down on seamounts. We also investigated plastic incidence in 2,243 animals (comprising 26 species) across remote South Atlantic oceanic food webs, ranging from plankton to seabirds. We found that plastics had been ingested by primary consumers (zooplankton) to top predators (seabirds) at high rates. These findings suggest that MPA status will not mitigate the threat of plastic proliferation to this rich, unique and threatened biodiversity.

Application of activated barrier hopping theory to viscoplastic modeling of glassy polymers.

An established statistical mechanical theory of amorphous polymer deformation has been incorporated as a plastic mechanism into a constitutive model and applied to a range of polymer mechanical deformations. The temperature and rate dependence of the tensile yield of PVC, as reported in early studies, has been modeled to high levels of accuracy. Tensile experiments on PET reported here are analyzed similarly and good accuracy is also achieved. The frequently observed increase in the gradient of the plot of yield stress against logarithm of strain rate is an inherent feature of the constitutive model. The form of temperature dependence of the yield that is predicted by the model is found to give an accurate representation. The constitutive model is developed in two-dimensional form and implemented as a user-defined subroutine in the finite element package ABAQUS. This analysis is applied to the tensile experiments on PET, in some of which strain is localized in the form of shear bands and necks. These deformations are modeled with partial success, though adiabatic heating of the instability causes inaccuracies for this isothermal implementation of the model. The plastic mechanism has advantages over the Eyring process, is equally tractable, and presents no particular difficulties in implementation with finite elements.