Revisiting Perdeck's massive avian migration experiments debunks alternative social interpretations.

Whether avian migrants can adapt to their changing world depends on the relative importance of genetic and environmental variation for the timing and direction of migration. In the classic series of field experiments on avian migration, A. C. Perdeck discovered that translocated juveniles failed to reach goal areas, whereas translocated adults performed 'true-goal navigation'. His translocations of > 14 000 common starlings (Sturnus vulgaris) suggested that genetic mechanisms guide juveniles into a population-specific direction, i.e. 'vector navigation'. However, alternative explanations involving social learning after release in juveniles could not be excluded. By adding historical data from translocation sites, data that was unavailable in Perdeck's days, and by integrated analyses including the original data, we could not explain juvenile migrations from possible social information upon release. Despite their highly social behaviour, our findings are consistent with the idea that juvenile starlings follow inherited information and independently reach their winter quarters. Similar to more solitarily migrating songbirds, starlings would require genetic change to adjust the migration route in response to global change.

Evaluation status of current and emerging minimally invasive robotic surgical platforms.

BACKGROUND: The rapid adoption of robotics within minimally invasive surgical specialties has also seen an explosion of new technology including multi- and single port, natural orifice transluminal endoscopic surgery (NOTES), endoluminal and "on-demand" platforms. This review aims to evaluate the validation status of current and emerging MIS robotic platforms, using the IDEAL Framework. METHODS: A scoping review exploring robotic minimally invasive surgical devices, technology and systems in use or being developed was performed, including general surgery, gynaecology, urology and cardiothoracics. Systems operating purely outside the abdomen or thorax and endoluminal or natural orifice platforms were excluded. PubMed, Google Scholar, journal reports and information from the public domain were collected. Each company was approached via email for a virtual interview to discover more about the systems and to quality check data. The IDEAL Framework is an internationally accepted tool to evaluate novel surgical technology, consisting of four stages: idea, development/exploration, assessment, and surveillance. An IDEAL stage, synonymous with validation status in this review, was assigned by reviewing the published literature. RESULTS: 21 companies with 23 different robotic platforms were identified for data collection, 13 with national and/or international regulatory approval. Of the 17 multiport systems, 1 is fully evaluated at stage 4, 2 are stage 3, 6 stage 2b, 2 at stage 2a, 2 stage 1, and 4 at the pre-IDEAL stage 0. Of the 6 single-port systems none have been fully evaluated with 1 at stage 3, 3 at stage 1 and 2 at stage 0. CONCLUSIONS: The majority of existing robotic platforms are currently at the preclinical to developmental and exploratory stage of evaluation. Using the IDEAL framework will ensure that emerging robotic platforms are fully evaluated with long-term data, to inform the surgical workforce and ensure patient safety.

Predictors to Private Practice Occupational Therapy Fieldwork Opportunities in Canada: New Evidence suggests New Solutions.

The study examined predictors to increasing and enhancing fieldwork education opportunities provided by occupational therapists working in private practice. A cross-sectional design that used a self-administered questionnaire was provided to Canadian occupational therapists in private practice. Participants receiving funding from the workers' compensation sector, those with between 11 and 20 years of work experience, and therapists working full-time hours were more likely to accept a student in fieldwork placement. Respondents who indicated that physical space and resources were not barriers to taking students on placement were more likely to accept students. Therapists more comfortable with the criteria and methods for appropriate and effective student teaching and supervision were also more likely to accept a student for fieldwork placement. The study findings can inform academic programs on how best to support preceptorship and guide university fieldwork coordinators' strategies for outreach and education for private practitioners.

Lyman-α source for laser cooling antihydrogen.

We present a Lyman-α laser developed for cooling trapped antihydrogen. The system is based on a pulsed Ti:sapphire laser operating at 729 nm that is frequency doubled using an LBO crystal and then frequency tripled in a Kr/Ar gas cell. After frequency conversion, this system produces up to 5.7 µW of average power at the Lyman-α wavelength. This laser is part of the ATRAP experiment at the antiproton decelerator in CERN.

The Impact of Alcohol Use on Drop-out and Psychological Treatment Outcomes in Improving Access to Psychological Therapies Services: an Audit.

BACKGROUND: The impact of alcohol use disorders (AUD) on psychological treatments for depression or anxiety in primary care psychological treatment services is unknown. AIMS: To establish levels of alcohol misuse in an Improving Access to Psychological Therapies (IAPT) service, examine the impact of higher risk drinking on IAPT treatment outcomes and drop-out, and to inform good practice in working with alcohol misuse in IAPT services. METHOD: 3643 patients completed a brief questionnaire on alcohol use pre-treatment in addition to measures of depression, anxiety and functioning. Symptom and functioning measures were re-administered at all treatment sessions. RESULTS: Severity of alcohol misuse was not associated with treatment outcomes, although those scoring eight or more on the AUDIT-C were more likely to drop out from treatment. CONCLUSIONS: IAPT services may be well placed to offer psychological therapies to patients with common mental disorders and comorbid AUD. Patients with AUD can have equivalent treatment outcomes to those without AUD, but some higher risk drinkers may find accessing IAPT treatment more difficult as they are more likely to drop out. Alcohol misuse on its own should not be used as an exclusion criterion from IAPT services. Recommendations are given as to how clinicians can: adjust their assessments to consider the appropriateness of IAPT treatment for patients that misuse alcohol, consider the potential impact of alcohol misuse on treatment, and improve engagement in treatment for higher risk drinkers.

Noncapped Alphavirus Genomic RNAs and Their Role during Infection.

UNLABELLED: Alphaviruses are enveloped positive-sense RNA viruses that exhibit a wide host range consisting of vertebrate and invertebrate species. Previously we have reported that the infectivity of Sindbis virus (SINV), the model alphavirus, was largely a function of the cell line producing the viral particles. Mammalian-cell-derived SINV particles, on average, exhibit a higher particle-to-PFU ratio than mosquito cell-derived SINV particles. Nevertheless, the outcome of nonproductive infection, the molecular traits that determine particle infectivity and the biological importance of noninfectious particles were, prior to this study, unknown. Here, we report that the incoming genomic RNAs of noninfectious SINV particles undergo rapid degradation following infection. Moreover, these studies have led to the identification of the absence of the 5' cap structure as a primary molecular determinant of particle infectivity. We show that the genomic RNAs of alphaviruses are not universally 5' capped, with a significant number of noncapped genomic RNA produced early in infection. The production of noncapped viral genomic RNAs is important to the establishment and maintenance of alphaviral infection. IMPORTANCE: This report is of importance to the field of virology for three reasons. First, these studies demonstrate that noncapped Sindbis virus particles are produced as a result of viral RNA synthesis. Second, this report is, to our knowledge, the first instance of the direct measurement of the half-life of an incoming genomic RNA from a positive-sense RNA virus. Third, these studies indicate that alphaviral infection is likely a concerted effort of infectious and noninfectious viral particles.

Comparing men's and women's experiences of work after cancer: a photovoice study.

PURPOSE: Work is an important quality of life indicator for many cancer survivors. There is, however, a lack of appropriate support to help survivors with work integration. As a result, many survivors are forced to independently navigate their return to work, experiencing unnecessary pitfalls in the process. As a preliminary step toward addressing this current gap in survivorship support, we explored the work integration experiences of 20 cancer survivors, 10 women and 10 men. METHODS: Photovoice methods were combined with two individual interviews per participant. Participant-produced photographs and interview transcripts were analyzed to identify key themes. RESULTS: Both commonalities and gender-differentiated motivations underlying work integration emerged. Female and male participants both demonstrated and discussed differentiated manners of coping. Men expressed a propensity for productivity and active engagements over talking used predominantly by women. CONCLUSION: Appreciation of men's proclivity for productivity and activity suggests that a gender-tailored approach to rehabilitation may enhance male survivors' participation and the utility of rehabilitation efforts.

GRP78 overproduction in pancreatic beta cells protects against high-fat-diet-induced diabetes in mice.

AIMS/HYPOTHESIS: Endoplasmic reticulum (ER) stress has been detected in pancreatic beta cells and in insulin-sensitive tissues, such as adipose and liver, in obesity-linked rodent models of type 2 diabetes. The contribution of ER stress to pancreatic beta cell dysfunction in type 2 diabetes is unclear. We hypothesised that increased chaperone capacity protects beta cells from ER stress and dysfunction caused by obesity and improves overall glucose homeostasis. METHODS: We generated a mouse model that overproduces the resident ER chaperone GRP78 (glucose-regulated protein 78 kDa) in pancreatic beta cells under the control of a rat insulin promoter. These mice were subjected to high-fat diet (HFD) feeding for 20 weeks and metabolic variables and markers of ER stress in islets were measured. RESULTS: As expected, control mice on the HFD developed obesity, glucose intolerance and insulin resistance. In contrast, GRP78 transgenic mice tended to be leaner than their non-transgenic littermates and were protected against development of glucose intolerance, insulin resistance and ER stress in islets. Furthermore, islets from transgenic mice had a normal insulin content and normal levels of cell-surface GLUT2 (glucose transporter 2) and the transgenic mice were less hyperinsulinaemic than control mice on the HFD. CONCLUSIONS/INTERPRETATION: These data show that increased chaperone capacity in beta cells provides protection against the pathogenesis of obesity-induced type 2 diabetes by maintaining pancreatic beta cell function, which ultimately improves whole-body glucose homeostasis.

Cervical cancer screening adherence among Somali immigrants and refugees to the United States.

Somali women have lower cervical cancer screening (CCS) rates than non-Somali women in the United States. We examined clinical and administrative data associated with CCS adherence among Somali women seen at a large primary care practice over 2 years. Fifty-one percent of 310 women were adherent to CCS, and adherence was associated with more overall health care system visits. Patients saw male providers 65.8% of the time; however, only 20.4% of the CCS tests were performed by male providers. Future interventions that enhance cancer prevention, health literacy, and patient-provider gender concordance may improve rates of CCS among Somali women.

Ketamine decreased opiate use in US military combat operations from 2010 to 2019.

BACKGROUND: Ketamine is a dissociative anaesthetic currently used in a variety of healthcare applications. Effects are dose dependent and cause escalating levels of euphoria, analgesia, dissociation and amnesia. Ketamine can be given via intravenous, intramuscular, nasal, oral and aerosolised routes. A 2012 memorandum and the 2014 Tactical Combat Casualty Care (TCCC) guidelines included ketamine as part of the 'Triple Option' for analgesia. This study investigated the effect of ketamine adoption by the US military TCCC guidelines on opioid use between 2010 and 2019. METHODS: This was a retrospective review of deidentified Department of Defense Trauma Registry data. The study was approved by the Institutional Review Board of Naval Medical Center San Diego (NMCSD) and facilitated by a data sharing agreement between NMCSD and the Defense Health Agency. Patient encounters from all US military operations from January 2010 to December 2019 were queried. All administrations of any pain medications via any route were included. RESULTS: 5965 patients with a total of 8607 pain medication administrations were included. Between 2010 and 2019, the yearly percentage of ketamine administrations rose from 14.2% to 52.6% (p<0.001). The percentage of opioid administrations decreased from 85.8% to 47.4% (p<0.001). Among the 4104 patients who received a single dose of pain medication, the mean Injury Severity Score for those who received ketamine was higher than for those who received an opioid (mean=13.1 vs 9.8, p<0.001). CONCLUSION: Military opioid use declined as ketamine use increased over 10 years of combat. Ketamine is generally used first for more severely injured patients and has increasingly been employed by the US military as the primary analgesic for combat casualties.

Bridging with glycoprotein IIb/IIIa inhibitors for periprocedural management of antiplatelet therapy in patients with drug eluting stents.

OBJECTIVE: To describe outcomes when glycoprotein IIb/IIIa (GP IIb/IIIa) inhibitors are used as bridging antiplatelet therapy for surgical procedures in patients with drug eluting stents (DES). BACKGROUND: The optimal management of patients with DES who require surgical procedures prior to completion of antiplatelet therapy is unclear. In high risk patients, the use of GP IIb/IIIa inhibitors as bridging therapy while antiplatelet therapy is held has been described, but safety and efficacy data remain sparse. METHODS: A pharmacy database was used to identify GP IIb/IIIa inhibitor orders at our hospital between January 1, 2007 and July 31, 2009. Indication for GP IIb/IIIa inhibitor administration and other clinical data were gathered through retrospective review of medical records. End points assessed were stent thrombosis, major bleeding, minor bleeding, postoperative acute coronary syndrome, and death within 30 days. RESULTS: Four thousand one hundred seventy-six separate orders for GP IIb/IIIa inhibitors were identified (January 1, 2007 to July 31, 2009). Six patients underwent non-cardiac and thirteen underwent cardiac surgery. Clopidogrel was discontinued a median of 6 days before surgery and 2 days prior to initiating GP IIb/IIIa inhibitor. All bridging patients were treated with eptifibatide infusion prior to procedure. There were no stent thromboses, deaths, or acute coronary syndrome events. Major bleeding occurred in 7 (53.9%) cardiac surgery patients and none of the non-cardiac surgery patients, while minor bleeding occurred in 1 (7.7%) and 1 (16.6%) patients, respectively. CONCLUSIONS: In patients with DES, who require cessation of clopidogrel before surgery, bridging with GP IIb/IIIa inhibitors appears effective in preventing adverse cardiac outcomes but may be associated with bleeding in patients undergoing cardiac surgery.

Diabetes care among Somali immigrants and refugees.

The risk for development of diabetes and associated complications among immigrants increases in the years after arrival to the United States. Somali immigrants and refugees represent the largest subset of African immigrants to the United States, yet little is known about the quality of their diabetes care. Therefore, adherence with diabetes quality indicators (Hemoglobin A1C <7%, LDL cholesterol <100 mg/dl, blood pressure <130/80 mm Hg) were compared between Somali and non-Somali patients with diabetes at a large academic primary care practice in the United States in 2008. Demographic and health-seeking behavior variables were assessed for association with adherence among the Somali population. A total of 5,843 non-Somali and 81 Somali patients with diabetes were identified. Somali patients with diabetes were less likely to meet the criteria for optimal glycemic control than non-Somali patients (40.6% vs. 53.9%; P=0.02). There was a similar, though statistically non-significant, trend towards lower rates of lipid control among Somali patients. There was no difference in achievement of optimal blood pressure between the two groups. There was a strong association between number of primary care visits during the study interval and achievement of all three diabetes care quality goals. This study demonstrates disparities in achievement of diabetes management quality goals among Somali patients compared with non-Somali patients, highlighting the need for additional system and practice changes to target this particularly vulnerable population.

High performance multilayered nano-crystalline silicon/silicon-oxide light-emitting diodes on glass substrates.

A low-temperature hydrogenation-assisted sequential deposition and crystallization technique is reported for the preparation of nano-scale silicon quantum dots suitable for light-emitting applications. Radio-frequency plasma-enhanced deposition was used to realize multiple layers of nano-crystalline silicon while reactive ion etching was employed to create nano-scale features. The physical characteristics of the films prepared using different plasma conditions were investigated using scanning electron microscopy, transmission electron microscopy, room temperature photoluminescence and infrared spectroscopy. The formation of multilayered structures improved the photon-emission properties as observed by photoluminescence and a thin layer of silicon oxy-nitride was then used for electrical isolation between adjacent silicon layers. The preparation of light-emitting diodes directly on glass substrates has been demonstrated and the electroluminescence spectrum has been measured.

Low mood and challenging behaviour in people with severe and profound intellectual disabilities.

BACKGROUND: We investigated the relationship between low mood and challenging behaviour in people in the severe and profound range of intellectual disability, while controlling for the presence of potentially confounding variables such as diagnosis of autism, physical and sensory problems and ill health. METHODS: The key workers of 52 people with severe and profound intellectual disability completed measures of depression, communication, challenging behaviour and provided information on relevant demographic and health variables. RESULTS: Using the Mood, Interest and Pleasure Questionnaire for classification of mood, a significant difference was found between a 'low mood' and 'normothymic' group in the reported occurrence of challenging behaviour. This difference remained even when confounding variables such as the presence of autism, health and sensory difficulties were controlled. The frequency and severity of challenging behaviour was predicted by measures indicating the presence of low mood. CONCLUSION: People with severe and profound show clear and measurable signs of low mood, and in this relatively small sample of institutionalised individuals, low mood was associated with challenging behaviour.

Homocystinuria patient and caregiver survey: experiences of diagnosis and patient satisfaction.

BACKGROUND: The main genetic causes of homocystinuria are cystathionine beta-synthase (CBS) deficiency and the remethylation defects. Many patients present in childhood but milder forms may present later in life. Some countries have newborn screening programs for the homocystinurias but these do not detect all patients. RESULTS: HCU Network Australia is one of the very few support groups for patients with homocystinurias. Here we report the results of its survey of 143 patients and caregivers from 22 countries, evaluating current diagnostic pathways and management for the homocystinurias. Most (110) of the responses related to patients with CBS deficiency. The diagnosis was made by newborn screening in 20% of patients and in 50% of the others within 1 year of the initial symptom but in 12.5% it took over 15 years. The delay was attributed mainly to ignorance of the disease. Physicians need to learn to measure homocysteine concentrations in children with neurodevelopmental problems, and in patients with heterogeneous symptoms such as thromboembolism, dislocation of the optic lens, haemolytic uraemic syndrome, and psychiatric disease. Even when the diagnosis is made, the way it is communicated is sometimes poor. Early-onset CBS deficiency usually requires a low-protein diet with amino acid supplements. More than a third of the participants reported problems with the availability or cost of treatment. Only half of the patients always took their amino acid mixture. In contrast, good adherence to the protein restriction was reported in 98% but 80% said it was hard, time-consuming and caused unhappiness. CONCLUSIONS: There is often a long delay in diagnosing the homocystinurias unless this is achieved by newborn screening; this survey also highlights problems with the availability and cost of treatment and the palatability of protein substitutes.

Precision medicine in human heart modeling : Perspectives, challenges, and opportunities.

Precision medicine is a new frontier in healthcare that uses scientific methods to customize medical treatment to the individual genes, anatomy, physiology, and lifestyle of each person. In cardiovascular health, precision medicine has emerged as a promising paradigm to enable cost-effective solutions that improve quality of life and reduce mortality rates. However, the exact role in precision medicine for human heart modeling has not yet been fully explored. Here, we discuss the challenges and opportunities for personalized human heart simulations, from diagnosis to device design, treatment planning, and prognosis. With a view toward personalization, we map out the history of anatomic, physical, and constitutive human heart models throughout the past three decades. We illustrate recent human heart modeling in electrophysiology, cardiac mechanics, and fluid dynamics and highlight clinically relevant applications of these models for drug development, pacing lead failure, heart failure, ventricular assist devices, edge-to-edge repair, and annuloplasty. With a view toward translational medicine, we provide a clinical perspective on virtual imaging trials and a regulatory perspective on medical device innovation. We show that precision medicine in human heart modeling does not necessarily require a fully personalized, high-resolution whole heart model with an entire personalized medical history. Instead, we advocate for creating personalized models out of population-based libraries with geometric, biological, physical, and clinical information by morphing between clinical data and medical histories from cohorts of patients using machine learning. We anticipate that this perspective will shape the path toward introducing human heart simulations into precision medicine with the ultimate goals to facilitate clinical decision making, guide treatment planning, and accelerate device design.

Short-form measures of diabetes-related emotional distress: the Problem Areas in Diabetes Scale (PAID)-5 and PAID-1.

AIMS/HYPOTHESIS: We wanted to identify a five-item short form of the Problem Areas in Diabetes Scale and a single-item measure for rapid screening of diabetes-related emotional distress. METHODS: Using an existing database of 1,153 patients with diabetes, we conducted a principal-components analysis to identify a set of five items and then conducted a reliability analysis and validity checks. From those five items, we identified the item with the strongest psychometric properties as a one-item screening tool. RESULTS: We identified a reliable and valid short version of the Problem Areas in Diabetes Scale (PAID) comprising five of the emotional-distress questions of the full PAID items (PAID-5, with items 3, 6, 12, 16, 19). The PAID-5 has satisfactory sensitivity (94%) and specificity (89%) for recognition of diabetes-related emotional distress. We also identified a one-item screening tool, the PAID-1 (Question 12: Worrying about the future and the possibility of serious complications), which has concurrent sensitivity and specificity of about 80% for the recognition of diabetes-related emotional distress. CONCLUSIONS/INTERPRETATION: The PAID-5 and PAID-1 appear to be psychometrically robust short-form measures of diabetes-related emotional distress.

Risk factors for implantable defibrillator lead fracture in a recalled and a nonrecalled lead.

INTRODUCTION: The Medtronic Sprint Fidelis implantable cardioverter defibrillator (ICD) lead was "recalled" in October 2007 after 268,000 implants worldwide due to increased failure risk. Manufacturer suggested monitoring has not been shown effective at preventing adverse events. Only limited data exist regarding clinical predictors of Fidelis lead fracture. We sought to identify risk factors for Fidelis fracture to guide clinical monitoring and compare its performance with a control lead. METHODS: Fractured lead cases were retrospectively reviewed for demographic data, implant technique, radiographic appearance and clinical presentation was analyzed. Lead survival was compared using Kaplan-Meir curves. RESULTS: Study patients (n = 1314) experienced 18 Fidelis and 6 Quattro lead fractures. Patients with failed Fidelis leads were younger than those with surviving leads (49.5 vs 64.6 years, P = 0.0066). Fidelis lead fractures often occurred around the time of physical activity. No other measured demographic or technique related factors were associated with lead fracture. Fidelis leads had significantly decreased survival compared with Quattro leads (89.3 vs 98.9% at 30 months). Patients less than 50 years old had significantly decreased lead survival compared with those older than 50 in both Fidelis (79.6% vs 96.5% at 24 months) and Quattro (93.4 vs 99.8%, P < 0.001 at 24 months) leads. CONCLUSIONS: Patients under age 50, with either Fidelis or Quattro ICD leads, are at increased risk of lead fracture compared with patients over 50, particularly around the time of intense physical activity. Aggressive monitoring and advisory programming appears warranted in patients with Fidelis leads as well as especially in younger patients.

Incidence of side effects using carbon dioxide-oxygen foam for chemical ablation of superficial veins of the lower extremity.

OBJECTIVES: To determine the incidence of side effects following treatment of varicose veins with carbon dioxide-oxygen (CO(2)/O(2)) foam sclerotherapy, and to compare results with historical controls using CO(2)- or air-based foams. DESIGN: Cohort study with prospective data collection, private clinic setting. PATIENTS: The patient population consisted of one hundred patients, 95% women, age 52 SD 13 years-old, CEAP class C(2)EpAsPr. METHODS: Patients underwent ultrasound-guided foam sclerotherapy following thermal ablation of saphenous trunks; 1-3% polidocanol and 70%CO(2)-30%O(2) gas were mixed in a 1:4 proportion. Volume injected averaged 22 SD 11 (range: 2-46) mL. Vital signs were monitored for 1 h; side effects were recorded up to 24 h post treatment. Incidence of side effects was compared to CO(2)- and air-based foam data. RESULTS: Heart rate decreased from 73 SD 11 at the start to 68 SD 9 bpm (p < 0.001, paired t-test) following the procedure. Systolic and diastolic pressures, 127/75 SD 18/14 mmHg, respiratory rate, 15 SD 4 rpm and pO(2), 98 SD 2%, did not change significantly. Itching (7) or leg pain (24) reporting was similar to that for air-based foam (p = NS). Lack of reported chest tightness and/or dry cough was superior to our previous data with CO(2) or air foam (p < 0.05). Reporting of dizziness (1) was less than that for air-based foam (p = 0.002). The incidence of visual disturbance (2%), was comparable with that for CO(2) (3%) or air (8%) foam, but too few cases were available for meaningful statistical analysis. CONCLUSIONS: Foam sclerotherapy using CO(2)/O(2) foam was well tolerated by patients and resulted in fewer side effects than similar treatment using air foams.

Integration of membrane proteins into the endoplasmic reticulum requires GTP.

We have examined the requirement for ribonucleotides and ribonucleotide triphosphate hydrolysis during early events in the membrane integration of two membrane proteins: the G protein of vesicular stomatitis virus and the hemagglutinin-neuraminidase (HN) glycoprotein of Newcastle disease virus. Both proteins contain a single transmembrane-spanning segment but are integrated in the membrane with opposite orientations. The G protein has an amino-terminal signal sequence and a stop-transfer sequence located near the carboxy terminus. The HN glycoprotein has a single sequence near the amino terminus that functions as both a signal-sequence and a transmembrane-spanning segment. Membrane insertion was explored using a cell-free system directed by transcribed mRNAs encoding amino-terminal segments of the two proteins. Ribosome-bound nascent polypeptides were assembled, ribonucleotides were removed by gel filtration chromatography, and the ribosomes were incubated with microsomal membranes under conditions of defined ribonucleotide content. Nascent chain insertion into the membrane required the presence of both the signal recognition particle and a functional signal recognition particle receptor. In the absence of ribonucleotides, insertion of nascent membrane proteins was not detected. GTP or nonhydrolyzable GTP analogues promoted efficient insertion, while ATP was comparatively ineffective. Surprisingly, the majority of the HN nascent chain remained ribosome associated after puromycin treatment. Ribosome-associated HN nascent chains remained competent for membrane insertion, while free HN chains were not competent. We conclude that a GTP binding protein performs an essential function during ribosome-dependent insertion of membrane proteins into the endoplasmic reticulum that is unrelated to protein synthesis.