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.

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.

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.

Life without a brain: Neuroradiological and behavioral evidence of neuroplasticity necessary to sustain brain function in the face of severe hydrocephalus.

A two-year old rat, R222, survived a life-time of extreme hydrocephaly affecting the size and organization of its brain. Much of the cortex was severely thinned and replaced by cerebrospinal fluid, yet R222 had normal motor function, could hear, see, smell, and respond to tactile stimulation. The hippocampus was malformed and compressed into the lower hindbrain together with the hypothalamus midbrain and pons, yet R222 showed normal spatial memory as compared to age-matched controls. BOLD MRI was used to study the reorganization of R222's brain function showing global activation to visual, olfactory and tactile stimulation, particularly in the brainstem/cerebellum. The results are discussed in the context of neuroadaptation in the face of severe hydrocephaly and subsequent tissue loss, with an emphasis on what is the "bare minimum" for survival.

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.

Improving network approaches to the study of complex social-ecological interdependencies.

Achieving effective, sustainable environmental governance requires a better understanding of the causes and consequences of the complex patterns of interdependencies connecting people and ecosystems within and across scales. Network approaches for conceptualizing and analyzing these interdependencies offer one promising solution. Here, we present two advances we argue are needed to further this area of research: (i) a typology of causal assumptions explicating the causal aims of any given network-centric study of social-ecological interdependencies; (ii) unifying research design considerations that facilitate conceptualizing exactly what is interdependent, through what types of relationships, and in relation to what kinds of environmental problems. The latter builds on the appreciation that many environmental problems draw from a set of core challenges that re-occur across contexts. We demonstrate how these advances combine into a comparative heuristic that facilitates leveraging case-specific findings of social-ecological interdependencies to generalizable, yet context-sensitive, theories based on explicit assumptions of causal relationships.

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 changing practice of transurethral resection of the prostate.

Introduction Transurethral resection of the prostate (TURP) is considered the gold standard surgical treatment for lower urinary tract symptoms (LUTS) secondary to benign prostatic hyperplasia. The number of TURPs performed has declined significantly over the last three decades owing to pharmaceutical therapy. TURP data from a single institution for the years 1990, 2000 and 2010 were compared to assess the difference in performance. Methods A retrospective analysis was undertaken of all patients who underwent TURP between January and December 2010. These findings were compared with historical data for the years 1990 and 2000: 100 sets of case notes were selected randomly from each of these years. Results The number of TURPs performed fell from 326 in 1990 to 113 in 2010. The mean age of patients increased from 70.6 years to 74.0 years. There was also a significant increase in the mean ASA grade from 1.9 to 2.3. The most common indication for TURP shifted from LUTS to acute urinary retention. No significant change in operating time was observed. The mean resection weight remained constant (22.95g in 1990, 22.55g in 2000, 20.76g in 2010). A reduction in transfusion rates was observed but there were higher rates of secondary haematuria and bladder neck stenosis. There was an increase from 2% to 11.5% of patients with long-term failure to void following TURP. Conclusions The number of TURPs performed continues to decline, which could lead to potential training issues. Urinary retention is still by far the most common indication. However, there has been a significant rise in the percentage of men presenting for TURP with high pressure chronic retention. The number of patients with bladder dysfunction who either have persistent storage LUTS or eventually require long-term catheterisation or intermittent self-catheterisation has increased markedly, which raises the question of what the long-term real life impact of medical therapy is on men with LUTS secondary to benign prostatic hyperplasia who eventually require surgery.

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.

Anabolic steroids alter the physiological activity of aggression circuits in the lateral anterior hypothalamus.

Syrian hamsters exposed to anabolic/androgenic steroids (AAS) during adolescence consistently show increased aggressive behavior across studies. Although the behavioral and anatomical profiles of AAS-induced alterations have been well characterized, there is a lack of data describing physiological changes that accompany these alterations. For instance, behavioral pharmacology and neuroanatomical studies show that AAS-induced changes in the vasopressin (AVP) neural system within the latero-anterior hypothalamus (LAH) interact with the serotonin (5HT) and dopamine (DA) systems to modulate aggression. To characterize the electrophysiological profile of the AAS aggression circuit, we recorded LAH neurons in adolescent male hamsters in vivo and microiontophoretically applied agonists and antagonists of aggressive behavior. The interspike interval (ISI) of neurons from AAS-treated animals correlated positively with aggressive behaviors, and adolescent AAS exposure altered parameters of activity in regular firing neurons while also changing the proportion of neuron types (i.e., bursting, regular, irregular). AAS-treated animals had more responsive neurons that were excited by AVP application, while cells from control animals showed the opposite effect and were predominantly inhibited by AVP. Both DA D2 antagonists and 5HT increased the firing frequency of AVP-responsive cells from AAS animals and dual application of AVP and D2 antagonists doubled the excitatory effect of AVP or D2 antagonist administration alone. These data suggest that multiple DA circuits in the LAH modulate AAS-induced aggressive responding. More broadly, these data show that multiple neurochemical interactions at the neurophysiological level are altered by adolescent AAS exposure.

Cancer survivors' concealment or disclosure of diagnosis: Implications for return to work.

BACKGROUND: The ability to return to work (RTW) is a significant quality of life indicator for many working aged cancer survivors. In the void of available support, many are left to independently navigate the RTW process which includes such important considerations as disclosure or concealment of diagnosis with concomitant sequellae. OBJECTIVE: This article reviews participants' variable approaches to concealment, disclosure, or even an open educative stance as well as the associated benefits and limitations. METHODS: Photovoice methods combined with interviewing. RESULTS: While most participants disclosed their diagnosis and many extolled the benefits of an open, educative stance, there were drawbacks experienced. Similarly, those who concealed their diagnosis also experienced benefits and challenges. CONCLUSIONS: In the current void of appropriate cancer rehabilitation supports, cancer survivors must independently negotiate their RTW process. Although most participants openly disclosed their diagnosis and associated limitations, a few concealed or camouflaged. There are benefits and limitations to both approaches of which survivors should be made aware at the outset as such will shape their RTW experience. Multidisciplinary rehabilitation support services would best guide survivors' management of the myriad of factors that will impact their work reintegration.

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.

Mesenchymal stromal cells for treatment of the acute respiratory distress syndrome: The beginning of the story.

In spite of decades of research, the acute respiratory distress syndrome (ARDS) continues to have an unacceptably high mortality and morbidity. Mesenchymal stromal cells (MSCs) present a promising candidate for the treatment of this condition and have demonstrated benefit in preclinical models. MSCs, which are a topic of growing interest in many inflammatory disorders, have already progressed to early phase clinical trials in ARDS. While a number of their mechanisms of effect have been elucidated, a better understanding of the complex actions of these cells may pave the way for MSC modifications, which might enable more effective translation into clinical practice.

Estradiol promotes pentose phosphate pathway addiction and cell survival via reactivation of Akt in mTORC1 hyperactive cells.

Lymphangioleiomyomatosis (LAM) is a female-predominant interstitial lung disease that can lead to respiratory failure. LAM cells typically have inactivating TSC2 mutations, leading to mTORC1 activation. The gender specificity of LAM suggests that estradiol contributes to disease development, yet the underlying pathogenic mechanisms are not completely understood. Using metabolomic profiling, we identified an estradiol-enhanced pentose phosphate pathway signature in Tsc2-deficient cells. Estradiol increased levels of cellular NADPH, decreased levels of reactive oxygen species, and enhanced cell survival under oxidative stress. Mechanistically, estradiol reactivated Akt in TSC2-deficient cells in vitro and in vivo, induced membrane translocation of glucose transporters (GLUT1 or GLUT4), and increased glucose uptake in an Akt-dependent manner. (18)F-FDG-PET imaging demonstrated enhanced glucose uptake in xenograft tumors of Tsc2-deficient cells from estradiol-treated mice. Expression array study identified estradiol-enhanced transcript levels of glucose-6-phosphate dehydrogenase (G6PD), the rate-limiting enzyme of the pentose phosphate pathway. Consistent with this, G6PD was abundant in xenograft tumors and lung metastatic lesions of Tsc2-deficient cells from estradiol-treated mice. Molecular depletion of G6PD attenuated estradiol-enhanced survival in vitro, and treatment with 6-aminonicotinamide, a competitive inhibitor of G6PD, reduced lung colonization of Tsc2-deficient cells. Collectively, these data indicate that estradiol promotes glucose metabolism in mTORC1 hyperactive cells through the pentose phosphate pathway via Akt reactivation and G6PD upregulation, thereby enhancing cell survival under oxidative stress. Interestingly, a strong correlation between estrogen exposure and G6PD was also found in breast cancer cells. Targeting the pentose phosphate pathway may have therapeutic benefit for LAM and possibly other hormonally dependent neoplasms.

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.

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.