Uptake and performance of prevention of mother-to-child transmission and early infant diagnosis in pregnant HIV-infected women and their exposed infants at seven health centres in Addis Ababa, Ethiopia.
To assess the uptake of WHO-recommended PMTCT procedures in Ethiopia's health services. Prospective observational study of HIV-positive pregnant mothers and their newborns attending PMTCT services at seven health centres in Addis Ababa. Women were recruited during antenatal care and followed up with their newborns at delivery, Day 6 and Week 6 post-partum. Retention to PMCTC procedures, self-reported antiretroviral treatment (ART) adherence and HIV infant outcome were assessed. Turnaround times of HIV early infant diagnosis (EID) procedures were extracted from health registers. Of 494 women enrolled, 4.9% did not complete PMTCT procedures due to active denial or loss to follow-up. HIV was first diagnosed in 223 (45.1%) and ART initiated in 321 (65.0%) women during pregnancy. ART was initiated in a median of 1.3 weeks (IQR 0-4.3) after HIV diagnosis. Poor self-reported treatment adherence was higher post-partum than during pregnancy (12.5% vs. 7.0%, P = 0.002) and significantly associated with divorced/separated marital status (RR 2.2, 95% CI 1.3-3.8), low family income (RR 2.1, 95% CI 1.1-4.1), low CD4 count (RR 1.7, 95% CI 1.0-3.0) and ART initiation during delivery (RR 2.5, 95% CI 1.1-5.6). Of 435 infants born alive, 98.6% received nevirapine prophylaxis. The mother-to-child HIV transmission rate was 0.7% after a median of 6.7 weeks (IQR 6.4-10.4), but EID results were received for only 46.6% within 3 months of birth. High retention in PMTCT services, triple maternal ART and high infant nevirapine prophylaxis coverage were associated with low mother-to-child HIV transmission. Declining post-partum ART adherence and challenges of EID linkage require attention.


Effect of Liquid Electrolyte Soaking on the Interfacial Resistance of Li7La3Zr2O12 for All-Solid-State Lithium Batteries.
The impact of liquid electrolyte soaking on the interfacial resistance between the garnet-structured Li7La3Zr2O12 (LLZO) solid electrolyte and metallic lithium has been studied. Lithium carbonate (Li2CO3) formed by inadvertent exposure of LLZO to ambient conditions is generally known to increase interfacial impedance and decrease lithium wettability. Soaking LLZO powders and pellets in the electrolyte containing lithium tetrafluoroborate (LiBF4) shows a significantly reduced interfacial resistance and improved contact between lithium and LLZO. Raman spectroscopy, X-ray diffraction, and soft X-ray absorption spectroscopy reveal how Li2CO3 is continuously removed with increasing soaking time. On-line mass spectrometry and free energy calculations show how LiBF4 reacts with surface carbonate to form carbon dioxide. Using a very simple and scalable process that does not involve heat-treatment and expensive coating techniques, we show that the Li-LLZO interfacial resistance can be reduced by an order of magnitude.


Tetracyclines and prion infectivity.
In the last decade information has accumulated on the potential anti-prion activity of polycyclic compounds. Initially we showed that the antitumoral idodoxorubicin reduced the infectivity in experimental scrapie. On the basis of the chemical homology with anthracyclines, we rapidly moved to tetracyclines, compounds that are safer and widely used as antibiotics in clinical practice. The tetracyclines, essentially doxycycline and minocycline, were characterized as a therapeutical tool in transmissible spongiform encephalopathies (TSE) through the cell-free condition, in cellular and animal models and they are now being investigated clinically with this indication. Tetracyclines interact with aggregates obtained by synthetic PrP peptides or pathological PrP (PrPsc) extracted from TSE brains, and they destabilize the structure of amyloid fibrils, reducing their resistance to digestion by proteinase K. Tetracyclines also interact with peptide oligomeric structures and inhibit the protein misfolding associated with PrPsc formation. These activities have been accompanied by a reduction of infectivity, verified by doxycycline treatment in experimental scrapie, and some curative effects after either peripheral or intracerebral infection. The anti-amyloidogenic activity of tetracyclines was tested in other forms of peripheral and central amyloidosis, with interesting results. This article analyzes the development of tetracyclines as a therapeutic tool in TSE in the light of recent results obtained in our laboratories.


White matter microstructural differences underlying beta oscillations during speech in adults who stutter.
The basal ganglia-thalamocortical (BGTC) loop may underlie speech deficits in developmental stuttering. In this study, we investigated the relationship between abnormal cortical neural oscillations and structural integrity alterations in adults who stutter (AWS) using a novel magnetoencephalography (MEG) guided tractography approach. Beta oscillations were analyzed using sensorimotor speech MEG, and white matter pathways were examined using tract-based spatial statistics (TBSS) and probabilistic tractography in 11 AWS and 11 fluent speakers. TBSS analysis revealed overlap between cortical regions of increased beta suppression localized to the mouth motor area and a reduced fractional anisotropy (FA) in the AWS group. MEG-guided tractography showed reduced FA within the BGTC loop from left putamen to subject-specific MEG peak. This is the first study to provide evidence that structural abnormalities may be associated with functional deficits in stuttering and reflect a network deficit within the BGTC loop that includes areas of the left ventral premotor cortex and putamen.


Nonlinear Mixed-effect Models for Prostate-specific Antigen Kinetics and Link with Survival in the Context of Metastatic Prostate Cancer: A Comparison by Simulation of Two-stage and Joint Approaches.
In metastatic castration-resistant prostate cancer (mCRPC) clinical trials, the assessment of treatment efficacy essentially relies on the time to death and the kinetics of prostate-specific antigen (PSA). Joint modeling has been increasingly used to characterize the relationship between a time to event and a biomarker kinetics, but numerical difficulties often limit this approach to linear models. Here, we evaluated by simulation the capability of a new feature of the Stochastic Approximation Expectation-Maximization algorithm in Monolix to estimate the parameters of a joint model where PSA kinetics was defined by a mechanistic nonlinear mixed-effect model. The design of the study and the parameter values were inspired from one arm of a clinical trial. Increasingly high levels of association between PSA and survival were considered, and results were compared with those found using two simplified alternatives to joint model, a two-stage and a joint sequential model. We found that joint model allowed for a precise estimation of all longitudinal and survival parameters. In particular, the effect of PSA kinetics on survival could be precisely estimated, regardless of the strength of the association. In contrast, both simplified approaches led to bias on longitudinal parameters, and two-stage model systematically underestimated the effect of PSA kinetics on survival. In summary, we showed that joint model can be used to characterize the relationship between a nonlinear kinetics and survival. This opens the way for the use of more complex and physiological models to improve treatment evaluation and prediction in oncology.


Recognition and diagnosis of tardive dyskinesia.
The recognition of specific types of abnormal movements in patients receiving chronic neuroleptic therapy is discussed. Characteristics of the four major categories of such movements--tremor, chorea, tics, and dystonia--are listed. These abnormal movements can be seen in several other syndromes and disease processes, which are briefly reviewed.


scTopoGAN: unsupervised manifold alignment of single-cell data.
Single-cell technologies allow deep characterization of different molecular aspects of cells. Integrating these modalities provides a comprehensive view of cellular identity. Current integration methods rely on overlapping features or cells to link datasets measuring different modalities, limiting their application to experiments where different molecular layers are profiled in different subsets of cells. We present scTopoGAN, a method for unsupervised manifold alignment of single-cell datasets with non-overlapping cells or features. We use topological autoencoders (topoAE) to obtain latent representations of each modality separately. A topology-guided Generative Adversarial Network then aligns these latent representations into a common space. We show that scTopoGAN outperforms state-of-the-art manifold alignment methods in complete unsupervised settings. Interestingly, the topoAE for individual modalities also showed better performance in preserving the original structure of the data in the low-dimensional representations when compared to other manifold projection methods. Taken together, we show that the concept of topology preservation might be a powerful tool to align multiple single modality datasets, unleashing the potential of multi-omic interpretations of cells. Implementation available on GitHub (https://github.com/AkashCiel/scTopoGAN). All datasets used in this study are publicly available.


Relational memory in psychotic bipolar disorder.
Recent research has highlighted the phenotypic and genetic overlap of bipolar disorder and schizophrenia. Cognitive deficits in bipolar disorder parallel those seen in schizophrenia, particularly for bipolar disorder patients with a history of psychotic features. Here we explored whether relational memory deficits, which are prominent in schizophrenia, are also present in patients with psychotic bipolar disorder. We tested 25 patients with psychotic bipolar disorder on a relational memory paradigm previously employed to quantify deficits in schizophrenia. During the training, participants learned to associate a set of faces and background scenes. During the testing, participants viewed a single background overlaid by three trained faces and were asked to recall the matching face, which was either present (Match trials) or absent (Non-Match trials). Explicit recognition and eye-movement data were collected and compared to those for 28 schizophrenia patients and 27 healthy subjects from a previously published dataset. Contrary to our prediction, we found psychotic bipolar disorder patients were less impaired in relational memory than schizophrenia subjects. Bipolar disorder subjects showed eye-movement behavior similar to healthy controls, whereas schizophrenia subjects were impaired relative to both groups. However, bipolar disorder patients with current delusions and/or hallucinations were more impaired than bipolar disorder patients not currently experiencing these symptoms. We found that patients with psychotic bipolar disorder had better relational memory performance than schizophrenia patients, indicating that a history of psychotic symptoms does not lead to a significant relational memory deficit.


Azathioprine induced pancreatitis in a patient with co-existing autoimmune pancreatitis and hepatitis.
Azathioprine induced pancreatitis usually runs a benign self limited course with rapid disappearance of signs and symptoms upon with drawl of the drug. Azathioprine is used in treating relapses in patients with autoimmune pancreatitis and maintenance of remission in autoimmune hepatitis. Acute pancreatitis complicated by symptomatic pseudocysts requiring drainage is not usually associated with drug induced pancreatitis. The risk of azathioprine use in patients with underlying disease of pancreas including autoimmune pancreatitis is unclear. We report here a case of an African American patient with co-existing autoimmune pancreatitis and autoimmune hepatitis who developed azathioprine induced acute pancreatitis complicated by a large symptomatic pseudocyst compressing the duodenum requiring a cystoduodenostomy. Future studies to investigate the risk of azathioprine induced pancreatitis in the presence of underlying disease of the pancreas including autoimmune pancreatitis are required to further understand the safety of azathioprine in this sub group of patients.


Investigation of endogenous compounds for assessing the drug interactions in the urinary excretion involving multidrug and toxin extrusion proteins.
Multidrug and toxin extrusion proteins (MATEs) are multispecific organic cation transporters mediating the efflux of various cationic drugs into the urine. The present study aimed at identifying endogenous compounds in human plasma and urine specimens as biomarkers to evaluate drug interactions involving MATEs in the kidney without administration of their exogenous probe drugs. An untargeted metabolomic analysis was performed using urine and plasma samples from healthy volunteers and mice treated with or without the potent MATE inhibitor, pyrimethamine. Plasma and urinary concentrations of candidate markers were measured using liquid chromatography-mass spectrometry. Transport activities were determined in MATE- or OCT2-expressing HEK293 cells. The deuterium-labeled compounds of candidates were administered to mice for pharmacokinetics study. Urinary excretion of eleven compounds including thiamine and carnitine was significantly lower in the pyrimethamine-treatment group in humans and mice, whereas no endogenous compound was noticeably accumulated in the plasma. The renal clearance of thiamine and carnitine was decreased by 70%-84% and 90%-94% (p < 0.05), respectively, in human. The specific uptake of thiamine was observed in MATE1-, MATE2-K- or OCT2-expressing HEK293 cells with Km of 3.5 ± 1.0, 3.9 ± 0.8 and 59.9 ± 6.7 μM, respectively. The renal clearance of carnitine-d 3 was decreased by 62% in mice treated with pyrimethamine. Our findings indicate that MATEs account for the efflux of thiamine and perhaps carnitine as well as drugs into the urine. The urinary excretion of thiamine is useful to detect drug interaction involving MATEs in the kidney.


Angiotensin-converting enzyme gene polymophism in adult primary focal segmental glomerulosclerosis.
Primary focal segmental glomerulosclerosis (FSGS) accounts for a third of biopsy-proven primary glomerulonephritis in Malaysia. Pediatric studies have found the insertion/deletion (I/D) polymorphism of the angiotensin-converting enzyme (ACE) gene to be associated with renal disease progression. The aim of this study was to determine the prevalence of the ACE (I/D) genotypes in adult primary FSGS and its association with renal outcome on follow-up. Prospective observational study involving primary FSGS patients was conducted. Biochemical and urine tests at the time of study were compared to the time of the diagnosis and disease progression analyzed. ACE gene polymorphism was identified using polymerase chain reaction amplification technique and categorized into II, ID and DD genotypes. Forty-five patients with a median follow-up of 3.8 years (interquartile range: 1.8 - 5.6) were recruited. The commonest genotype was II (n = 23, 51.1%) followed by ID (n = 19, 42.2%) and DD (n = 3, 6.7%). The baseline characteristics were comparable between the II and non-II groups at diagnosis and at study recruitment except that the median urine protein-creatinine index was significantly lower in the II group compared to the non-II group (0.02 vs. 0.04 g/mmol (P = 0.03). Regardless of genotypes, all parameters of renal outcome improved after treatment. The II followed by ID genotypes were the predominant ACE gene alleles in our FSGS. Although the D allele has been reported to have a negative impact on renal outcome, treatment appeared to be more important than genotype in preserving renal function in this cohort.


Insertion of reticuloendotheliosis virus long terminal repeat into the genome of CVI988 strain of Marek's disease virus results in enhanced growth and protection.
Marek's disease (MD) is a lymphoproliferative disease of chickens caused by serotype 1 MD virus (MDV). Vaccination of commercial poultry has drastically reduced losses from MD, and the poultry industry cannot be sustained without the use of vaccines. Retrovirus insertion into herpesvirus genomes is an efficient process that alters the biological properties of herpesviruses. RM1, a virus derived from the virulent JM strain of MDV, by insertion of the reticuloendotheliosis (REV) long terminal repeat (LTR), was attenuated for oncogenicity but retains properties of the parental virus, such as lymphoid organ atrophy. Here we show that insertion of the REV LTR into the genome of vaccine strain CVI988 resulted in a virus (CVRM) that replicated to higher levels than parental CVI988 in cell culture and that remained apathogenic for chickens. In addition, CVRM showed protection indices similar or superior to those afforded by CVI988 virus in laboratory and field protection trials, indicating that it could be developed as a safe and efficacious vaccine to protect against very virulent plus MDV.


COVID-19 Vaccine Tweets After Vaccine Rollout: Sentiment-Based Topic Modeling.
COVID-19 vaccines are one of the most effective preventive strategies for containing the pandemic. Having a better understanding of the public's conceptions of COVID-19 vaccines may aid in the effort to promptly and thoroughly vaccinate the community. However, because no empirical research has yet fully explored the public's vaccine awareness through sentiment-based topic modeling, little is known about the evolution of public attitude since the rollout of COVID-19 vaccines. In this study, we specifically focused on tweets about COVID-19 vaccines (Pfizer, Moderna, AstraZeneca, and Johnson & Johnson) after vaccines became publicly available. We aimed to explore the overall sentiments and topics of tweets about COVID-19 vaccines, as well as how such sentiments and main concerns evolved. We collected 1,122,139 tweets related to COVID-19 vaccines from December 14, 2020, to April 30, 2021, using Twitter's application programming interface. We removed retweets and duplicate tweets to avoid data redundancy, which resulted in 857,128 tweets. We then applied sentiment-based topic modeling by using the compound score to determine sentiment polarity and the coherence score to determine the optimal topic number for different sentiment polarity categories. Finally, we calculated the topic distribution to illustrate the topic evolution of main concerns. Overall, 398,661 (46.51%) were positive, 204,084 (23.81%) were negative, 245,976 (28.70%) were neutral, 6899 (0.80%) were highly positive, and 1508 (0.18%) were highly negative sentiments. The main topics of positive and highly positive tweets were planning for getting vaccination (251,979/405,560, 62.13%), getting vaccination (76,029/405,560, 18.75%), and vaccine information and knowledge (21,127/405,560, 5.21%). The main concerns in negative and highly negative tweets were vaccine hesitancy (115,206/205,592, 56.04%), extreme side effects of the vaccines (19,690/205,592, 9.58%), and vaccine supply and rollout (17,154/205,592, 8.34%). During the study period, negative sentiment trends were stable, while positive sentiments could be easily influenced. Topic heatmap visualization demonstrated how main concerns changed during the current widespread vaccination campaign. To the best of our knowledge, this is the first study to evaluate public COVID-19 vaccine awareness and awareness trends on social media with automated sentiment-based topic modeling after vaccine rollout. Our results can help policymakers and research communities track public attitudes toward COVID-19 vaccines and help them make decisions to promote the vaccination campaign.


Altered cardiac autonomic function may precede insulin resistance in metabolic syndrome.
Previous studies on the change of cardiac autonomic function and insulin resistance in metabolic syndrome recruited subjects with cardiovascular-related disease and defined metabolic abnormality with a more severe cutoff. We explored the alteration of cardiac autonomic function and insulin resistance in predisease community dwellers with different numbers of metabolic abnormalities. A total of 1298 subjects were classified as none (n=539), one (n=378), 2 (n=218), and 3 or more metabolic abnormalities (n=154). Insulin resistance was calculated by homeostatic model assessment. Cardiac autonomic function included 5-minute standard deviation of R-R interval, low- and high-frequency power spectrum, and low-/high-frequency power spectrum ratio, the ratio of the longest R-R interval around the 30th beat and the shortest R-R interval around the 15th beat after standing, and the ratio of the longest expiratory R-R interval to the shortest inspiratory R-R interval during deep breathing. Subjects with a single metabolic abnormality or more had a lower standard deviation of R-R interval and expiratory/inspiratory ratio than subjects without metabolic abnormality in multivariate analysis. Subjects with 3 or more metabolic abnormalities had a higher low-/high-frequency power spectrum ratio, but a lower high-frequency power. Insulin resistance was higher in groups with 2 metabolic abnormalities or more, but not in the group with one metabolic abnormality, than those without metabolic abnormality. Cardiac autonomic function altered in predisease subjects with one or more metabolic abnormalities, while insulin resistance existed in subjects with 2 or more metabolic abnormalities. Thus, autonomic function change may precede insulin resistance in the initiation of metabolic syndrome.


Emergence and clinical insights into the pathology of Chikungunya virus infection.
Major epidemics of Chikungunya have re-emerged with millions of cases worldwide. What was once largely a tropical disease in poorer countries is now recognized as a major global health issue. The disease is perpetuated by the alphavirus Chikungunya, and is transmitted by Aedes mosquitoes. The infection is highly symptomatic, with fever, skin rash and incapacitating arthralgia, which can evolve to chronic arthritis and rheumatism in elderly patients. Mother-to-child transmission, encephalitis, Guillain-Barré syndrome and deaths have been noted. In this article, we will highlight the epidemiological, clinical, virological and immunological aspects of the disease and mention the therapies that have been used during recent epidemics. Novel prevention measures to control the mosquito and a new vaccine are highly warranted.


Disclosing errors to patients: perspectives of registered nurses.
Disclosure of medical errors has been conceptualized as occurring primarily in the physician-patient dyad. Yet, health care is delivered by interprofessional teams, in which nurses share in the culpability for errors, and hence, in responsibility for disclosure. This study explored nurses' perspectives on disclosure of errors to patients and the organizational factors that influence disclosure. Between October 2004 and December 2005, 11 focus groups were conducted with 96 registered nurses practicing in one of four health care organizations in the Puget Sound region of Washington State. Focus groups were analyzed using qualitative content analysis. Nurses reported routinely independently disclosing nursing errors that did not involve serious harm, but felt the attending physician should lead disclosures when patient harm had occurred or when errors involved the team. Nurses usually were not involved in the error disclosure discussion among the team to plan for the disclosure or in the actual disclosure, leading to ethically compromising situations in nurses' communication with patients and families. Awareness of existing error disclosure policies was low. Nonetheless, these nurses felt that hospital policies that fostered a collaborative process would be helpful. Nurse managers played a key role in creating a culture of transparency and in being a resource for error disclosures. Nurses conceived of the disclosure process as a team event occurring in the context of a complex health care system rather than as a physician-patient conversation. Nurses felt excluded from these discussions, resulting in their use of ethically questionable communication strategies. The findings underscore the need for organizations to adopt a team disclosure process. Health care organizations that integrate the entire health care team into the disclosure process will likely improve the quality of error disclosure.


Ifosfamide, epirubicin, etoposide (IEV) and autologous peripheral blood progenitor cell transplant: a feasible and effective salvage treatment for lymphoid malignancies.
The IEV schedule consisted of epirubicin 100 mg/m2 on day 1, etoposide 150 mg/m2 on days 1-3, and ifosfamide 2.5 g/m2 on days 1-3. Patients who proceeded to haematopoietic stem cell transplants (HDTs) received conditioning therapy with BEAM [for the Hodgkin's Lymphoma (HL) and non-Hodgkin's Lymphoma (NHL) groups], or melphalan 100 mg/m2 and mitoxantrone [for the multiple myeloma (MM) patients]. The study consisted of 65 patients with a median age of 53 years: 27 had aggressive NHL, 20 had HL, 7 had indolent NHL, and 11 had MM. Fifty-five patients received IEV for a disease that was refractory to conventional induction regimens, or that was in first or second relapse; 4 patients were treated with IEV while in complete response (CR) after chemotherapy in order to mobilise peripheral blood stem cells (PBSCs). Ninety percent of patients with HL responded to IEV, and 85% achieved CR. Both aggressive and indolent NHLs were less responsive (ORR 50 and 33%, respectively; CRR 41 and 16.5%, respectively). MM patients displayed an intermediate responsiveness (ORR 50% and CRR 30%). IEV was well tolerated in most patients. No life- threatening infections were recorded. PBSC mobilisation was successful in 37 out of 39 patients (95%) and led to the collection of a median of 16, 12, and 13.7 x 10(6) CD34+ cells/kg in patients with HL, NHL, and MM, respectively. All 37 patients underwent an autologous stem cell transplant following a 1 to 2 month interval after the end of IEV. Two patients were submitted to an allogeneic transplant. The median overall survival rate in HL, aggressive NHL, and indolent NHL is 32 (5-60), 16 (2-46), and 14 (4-42) months, respectively. Median EFS is 31 (5-60), 7 (2-46), and 7.5 (4-42) months, respectively. In conclusion, our study confirms that IEV +/- HDT is a well-tolerated and effective salvage treatment for lymphoid malignancies, and that IEV acts as an excellent stem cell mobiliser.


A tissue-specific, Gata6-driven transcriptional program instructs remodeling of the mature arterial tree.
Connection of the heart to the systemic circulation is a critical developmental event that requires selective preservation of embryonic vessels (aortic arches). However, why some aortic arches regress while others are incorporated into the mature aortic tree remains unclear. By microdissection and deep sequencing in mouse, we find that neural crest (NC) only differentiates into vascular smooth muscle cells (SMCs) around those aortic arches destined for survival and reorganization, and identify the transcription factor Gata6 as a crucial regulator of this process. Gata6 is expressed in SMCs and its target genes activation control SMC differentiation. Furthermore, Gata6 is sufficient to promote SMCs differentiation in vivo, and drive preservation of aortic arches that ought to regress. These findings identify Gata6-directed differentiation of NC to SMCs as an essential mechanism that specifies the aortic tree, and provide a new framework for how mutations in GATA6 lead to congenital heart disorders in humans.


Kidney transplant after hematopoietic cell transplant in pediatrics: Infectious and immunosuppressive considerations.
Pediatric patients requiring kidney transplant after hematopoietic cell transplant receive multiple courses of immunosuppression placing them at risk for infection. To elucidate potential risk factors for infection, we compared the immunosuppressive regimens and infectious complications of pediatric kidney transplant recipients at a single institution who had previously undergone hematopoietic cell transplant from different donors to similar patients reported in the literature. Among the initial four post-hematopoietic cell transplant kidney transplant patients reviewed, viremia episodes were universal, including BK virus, Epstein-Barr virus, and human herpesvirus-6, with one death from presumed BK virus encephalitis. No viremia was reported in five similar cases in the literature. Risk factors for increased infection include use of lymphodepleting serotherapy in HCT conditioning, multiple HCTs, limited immune reconstitution time between transplants, increased pre-KTx viral burden, and use of T-cell-depleting versus -suppressive induction immunosuppression for KTx. These findings suggest that pediatric post-HCT KTx recipients are at increased risk for viral infections, likely benefitting from thorough pre-KTx evaluation of immune reconstitution and preferential use of non-T-cell-depleting induction therapy for KTx. We applied these recommendations to one subsequent post-HCT patient requiring KTx at our institution with excellent outcomes one year post-KTx.


Empirical findings of fitness-for-duty evaluations.
This article was migrated. The article was marked as recommended. Background:The ability of physicians to practice appropriately is often evaluated by a fitness for duty exam. This report reviews the empirical literature on fitness for duty evaluations. Methods: A literature review was performed on PubMed using the terms physician, impairment, burnout, fitness to practice and fitness for duty. Results: At least one percent of physicians are referred each year for possibly serious difficulties. Surgery and its subspecialties and psychiatry may be at higher risk. Variables associated with fitness for duty evaluations include educational, personality, culture and emotional illness. Conclusions: Risk factors appear to vary between modifiable (training, culture and treatable emotional illness), less modifiable (personality) and likely unmodifiable (specialty). Fitness for duty should be part of the training of all psychiatrists.


ADHD Is Associated With a Widespread Pattern of Risky Behavior Across Activity Domains.
Objective: ADHD has been linked to higher engagement in risky behaviors in circumscribed domains such as dangerous driving, substance abuse, and gambling. This study tests whether ADHD is associated with a pervasive tendency to engage in risky behavior across a spectrum of activities and domains, and whether this tendency is driven by comorbid disorders. Method: A sample of 97 adults with ADHD and 103 typically developing controls completed a self-report questionnaire measuring the likelihood and frequency of engaging in a broad range of risky behaviors. ADHD, comorbid psychiatric disorders, and demographic variables were extensively assessed using standardized instruments. Results: Participants with ADHD reported a pervasive tendency to engage in risky behaviors across multiple activities. This tendency was associated with ADHD over and above the contribution of comorbid psychiatric disorders. Conclusion: These results suggest that ADHD is uniquely linked to a pervasive pattern of engagement in risky behaviors.


Breast cancer screening and cost-effectiveness; policy alternatives, quality of life considerations and the possible impact of uncertain factors.
Mammographic screening for women aged 50-70 is effective in reducing breast cancer mortality, but the impact on quality of life and the attainable mortality reduction remain to be discussed. The consequences of expanding screening programmes to include women in other age groups are uncertain. We have predicted the effects and costs for 5 popular screening variants, differing in age group and screening interval, on the basis of our analysis of the Dutch screening trials and of the reported mortality reductions in other trials. We have also investigated the influence of a large number of uncertain factors. Screening for women aged 50 and over with a 2- or 3-year interval is very cost-effective and will result in reductions of respectively 16% or 10% in breast cancer mortality in a real population. Variation of most variables keeps the cost-effectiveness (CE) ratio limited to the range of US $3,000 to 5,000 per life-year gained. A 2- to 3-fold change in CE ratio would only occur if the extreme estimates of mortality reduction in the Swedish screening trials were applied. The impact on quality of life (QoL) is limited: for the 2-yearly screening policy for women aged 50-70, the cost per Quality-Adjusted Life-Year (QALY) gained is 4,050, whereas the cost per life-year gained is US $3,825. The CE ratio for 2-yearly screening of women aged 40-70 is 5,400, but the additional cost per additional life-year gained is US $35,000. It would be preferable by far to extend the screening programme to women over the age of 70 or to shorten the screening interval for women aged 50-70. Screening performances, the demand for mammograms outside screening and the possibility of a survival improvement irrespective of screening have a strong impact on QoL and CE.


Linking ice accretion and crown structure: towards a model of the effect of freezing rain on tree canopies.
Despite a longstanding interest in variation in tree species vulnerability to ice storm damage, quantitative analyses of the influence of crown structure on within-crown variation in ice accretion are rare. In particular, the effect of prior interception by higher branches on lower branch accumulation remains unstudied. The aim of this study was to test the hypothesis that intra-crown ice accretion can be predicted by a measure of the degree of sheltering by neighbouring branches. Freezing rain was artificially applied to Acer platanoides L., and in situ branch-ice thickness was measured directly and from LiDAR point clouds. Two models of freezing rain interception were developed: 'IceCube', which uses point clouds to relate ice accretion to a voxel-based index (sheltering factor; SF) of the sheltering effect of branch elements above a measurement point; and 'IceTree', a simulation model for in silico evaluation of the interception pattern of freezing rain in virtual tree crowns. Intra-crown radial ice accretion varied strongly, declining from the tips to the bases of branches and from the top to the base of the crown. SF for branches varied strongly within the crown, and differences among branches were consistent for a range of model parameters. Intra-crown variation in ice accretion on branches was related to SF (R(2) = 0·46), with in silico results from IceTree supporting empirical relationships from IceCube. Empirical results and simulations confirmed a key role for crown architecture in determining intra-crown patterns of ice accretion. As suspected, the concentration of freezing rain droplets is attenuated by passage through the upper crown, and thus higher branches accumulate more ice than lower branches. This is the first step in developing a model that can provide a quantitative basis for investigating intra-crown and inter-specific variation in freezing rain damage.


Improved peripheral cortical bone geometry after surgical treatment of primary hyperparathyroidism in postmenopausal women.
Cortical bone geometry is one of the most important components of bone strength. Excess endogenous PTH or intermittent PTH administration affects cortical bone geometry; however, the changes in cortical bone geometry in patients with primary hyperparathyroidism (pHPT) after parathyroidectomy (PTX) remain unknown. The present study was performed to examine the longitudinal effects of treating endogenous PTH excess on cortical bone geometry in postmenopausal patients with pHPT by using peripheral quantitative computed tomography. Twenty postmenopausal pHPT patients and 30 postmenopausal control subjects matched for age participated in this study. Volumetric bone mineral density (vBMD), cortical bone geometric parameters, polar strength strain index, and polar cross-sectional moment of inertia were measured using peripheral quantitative computed tomography at the radius during the year after PTX. After 1 yr, total and cortical vBMD significantly increased after PTX in the pHPT group (2.9 and 1.6%, respectively), whereas they significantly decreased in the control group (-2.1 and -1.3%, respectively). Significant decreases in cortical thickness and area were observed in the control group (-3.0 and -2.5%, respectively). In contrast, the pHPT group showed increases in cortical thickness and area (8.5 and 7.6%, respectively) as well as polar strength strain index 1 year after PTX. The present longitudinal study showed significant beneficial changes in volumetric BMD, cortical bone geometry, and bone strength index after PTX in postmenopausal women with pHPT.


Does catheter insertion by nephrologists improve peritoneal dialysis utilization? A multicenter analysis.
In contrast to hemodialysis (HD), peritoneal dialysis (PD) remains an underutilized form of renal replacement therapy in the United States. Although a variety of factors have been deemed responsible, timely insertion of a PD catheter may also be a contributory factor. We conducted a multicenter analysis to examine whether the establishment of a program for PD catheter insertion by nephrologists has a positive impact on the growth in the number of patients using PD. Data for catheter insertion performed by nephrologists were collected from three centers. Any change in the prevalent PD population at each respective center was compared to the number of PD patients during the period having the traditional surgical approach. Nephrologists at the three centers used the peritoneoscopic technique and performed catheter insertion under local anesthesia. In center 1, the PD population remained stable at between 38 and 45 patients (approximately 16% of the total end-stage renal disease [ESRD] population) from 1993 to 2001. Nephrologists initiated a program for PD catheter insertion in 2001. The number of PD patients has increased to 101 (32% of the ESRD population). In center 2, the PD population remained stable at between 70 and 78 patients (approximately 17%) between 1988 and 1990. Catheter insertion by interventional nephrologists began in 1991. The number of PD patients has increased to 125 (22%). In center 3, the PD population remained at 20-30 patients (approximately 18%) between 1988 and 1991. Catheter placement by nephrologists was initiated in 1991. The number of PD patients increased to 97 (27%). Catheter insertion by interventional nephrologists was suspended in 2001. The number of PD patients has gradually declined to 25 (6%). This study suggests that catheter insertion by the nephrologist can have a positive impact on the utilization of PD.


Hybrid aeroacoustic approach for the efficient numerical simulation of human phonation.
A hybrid aeroacoustic approach was developed for the efficient numerical computation of human phonation. In the first step, an incompressible flow simulation on a three-dimensional (3 D) computational grid, which is capable of resolving all relevant turbulent scales, is performed using STARCCM+ and finite volume method. In the second step, the acoustic source terms on the flow grid are computed and a conservative interpolation to the acoustic grid is performed. Finally, the perturbed convective wave equation is solved to obtain the acoustic field in 3 D with the finite element solver CFS++. Thereby, the conservative transformation of the acoustic sources from the flow grid to the acoustic grid is a key step to allow coarse acoustic grids without reducing accuracy. For this transformation, two different interpolation strategies are compared and grid convergence is assessed. Overall, 16 simulation setups are compared. The initial (267 000 degrees of freedom) and the optimized (21 265 degrees of freedom) simulation setup were validated by measurements of a synthetic larynx model. To conclude, the total computational time of the acoustic simulation is reduced by 95% compared to the initial simulation setup without a significant reduction of accuracy, being 7%, in the frequency range of interest.


Analysis of heterologous taxadiene production in K- and B-derived Escherichia coli.
Taxa-4(5),11(12)-diene is the first dedicated intermediate in the metabolic pathway responsible for synthesizing the anticancer compound Taxol. In this study, the heterologous production of taxadiene was established in and analyzed between K- and B-derived Escherichia coli strains. First, recombinant parameters associated with precursor metabolism (the upstream methylerythritol phosphate (MEP) pathway) and taxadiene biosynthesis (the downstream pathway) were varied to probe the effect different promoters and cellular backgrounds have on taxadiene production. Specifically, upstream MEP pathway genes responsible for the taxadiene precursors, dimethylallyl diphosphate and isopentenyl diphosphate, were tested with an inducible T7 promoter system within K and B E. coli strains. Whereas, inducible T7, Trc, and T5 promoters were tested with the plasmid-borne geranylgeranyl diphosphate synthase and taxadiene synthase genes responsible for the downstream pathway. The K-derivative produced taxadiene roughly 2.5-fold higher than the B-derivative. A transcriptomics study revealed significant differences in pyruvate metabolism between the K and B strains, providing insight into the differences observed in taxadiene biosynthesis and targets for future metabolic engineering efforts. Next, the effect of temperature on cell growth and taxadiene production was analyzed in these two strains, revealing similar phenotypes between the two with 22°C as the optimal production temperature. Lastly, the effect of indole on cell growth was investigated between the two strains, showing that the K-derivative demonstrated greater growth inhibition compared to the B-derivative.


Association of objective sedentary behaviour and self-rated health in English older adults.
Reducing sedentary behaviour (SB) might improve the health of older adults. However, we know little about how objectively measured SB impacts on self-rated health in older adults. We aimed to explore the associations between objectively measured SB and self-rated health in English older adults. A random sub-sample of older adults (≥ 65 years old) from the 2008 Health Survey for England wore an ActiGraph GT1M accelerometer for 7 days. Self-rated health was measured using an item from the General Health Questionnaire. Linear regression and analysis of covariance were used to test the associations between percentage time spent in SB and mean daily minutes in SB and self-rated health (very good/good; fair; bad/very bad), adjusting for covariates. Valid accelerometry datasets were returned by 578 individuals. Significant negative associations between percentage time and mean daily minutes in SB and self-rated health were found. In particular, individuals spending reduced percentages of time being sedentary had higher self-rated health. In conclusion, SB appears to be associated with self-rated health in older people independently from MVPA. If longitudinal research could determine how changes in SB influence self-rated health as individuals' age, this might be an important lifestyle variable to target for health improvement.


Single-molecule spectroscopy reveals photosynthetic LH2 complexes switch between emissive states.
Photosynthetic organisms flourish under low light intensities by converting photoenergy to chemical energy with near unity quantum efficiency and under high light intensities by safely dissipating excess photoenergy and deleterious photoproducts. The molecular mechanisms balancing these two functions remain incompletely described. One critical barrier to characterizing the mechanisms responsible for these processes is that they occur within proteins whose excited-state properties vary drastically among individual proteins and even within a single protein over time. In ensemble measurements, these excited-state properties appear only as the average value. To overcome this averaging, we investigate the purple bacterial antenna protein light harvesting complex 2 (LH2) from Rhodopseudomonas acidophila at the single-protein level. We use a room-temperature, single-molecule technique, the anti-Brownian electrokinetic trap, to study LH2 in a solution-phase (nonperturbative) environment. By performing simultaneous measurements of fluorescence intensity, lifetime, and spectra of single LH2 complexes, we identify three distinct states and observe transitions occurring among them on a timescale of seconds. Our results reveal that LH2 complexes undergo photoactivated switching to a quenched state, likely by a conformational change, and thermally revert to the ground state. This is a previously unobserved, reversible quenching pathway, and is one mechanism through which photosynthetic organisms can adapt to changes in light intensities.


Modern Potentiometric Biosensing Based on Non-Equilibrium Measurement Techniques.
Modern potentiometric sensors based on polymeric membrane ion-selective electrodes (ISEs) have achieved new breakthroughs in sensitivity, selectivity, and stability and have extended applications in environmental surveillance, medical diagnostics, and industrial analysis. Moreover, nonclassical potentiometry shows promise for many applications and opens up new opportunities for potentiometric biosensing. Here, we aim to provide a concept to summarize advances over the past decade in the development of potentiometric biosensors with polymeric membrane ISEs. This Concept article articulates sensing mechanisms based on non-equilibrium measurement techniques. In particular, we emphasize new trends in potentiometric biosensing based on attractive dynamic approaches. Representative examples are selected to illustrate key applications under zero-current conditions and stimulus-controlled modes. More importantly, fruitful information obtained from non-equilibrium measurements with dynamic responses can be useful for artificial intelligence (AI). The combination of ISEs with advanced AI techniques for effective data processing is also discussed. We hope that this Concept will illustrate the great possibilities offered by non-equilibrium measurement techniques and AI in potentiometric biosensing and encourage further innovations in this exciting field.


Refractory Lesional Parietal Lobe Epilepsy: Clinical, Electroencephalographic and Neurodiagnostic Findings.
Specialized centers, in the management and surgical treatment of medically refractory epilepsy, emphasize the importance of differentiating the varieties of localization related epilepsies. There has been considerable recent interest in temporal and frontal lobe epileptic syndromes and less attention has been paid to parietal and occipital lobe epilepsies. Here we report the clinical, electroencephalographic and neuroimaging characteristics of 46 patients with medically refractory lesional parietal lobe epilepsy who have been followed up for 1-10 years. In this study auras were reported in 78.3% of the patients and included sensory symptoms (72.2%), headache (36.1%), nausea and vomiting (36.1%), psychic symptoms (36.1%) and visual symptoms (16.6%). The most common ictal behavioral changes were paresthesia (69.6%) and focal clonic activity (39.1%). Tonic posture, various automatisms, head deviation, staring, sensation of pain and speech disturbances occurred to a lesser extent. Simple partial seizures were present in 69.6%. Complex partial seizures occurred in 43.5% and secondary generalized tonic clonic seizures were reported in 58.7% of the patients. Interictal routine EEG disclosed abnormal background activity in 1/3 of the patients. Nonlocalising epileptiform abnormalities were found in 34.8% of the patients. EEG findings were normal in 34.8% of the patients. The most common presumed etiologic factors were as follows: posttraumatic encephalomalacia, stroke, tumor, malformation of cortical development, atrophy, and arteriovenous malformation. Clinical, electrophysiological and neuroimaging features of the lesional symptomatic partial epilepsy patients may help us to localize the seizure focus in some patients with cryptogenic partial epilepsy. So that, the timing decision of the parietal lobe sampling with more invasive techniques like intracranial electrodes prior to epilepsy surgery would be easier.


Popliteal artery entrapment syndrome secondary to a femoral osteochondroma.
Osteochondromas (or exostoses) are the most common benign tumors of the bone. Vascular complications of these tumors are rare but have been increasingly reported in recent literature. Throughout an unusual case report of popliteal artery entrapment syndrome secondary to a femoral osteochondroma, we highlight the necessity of thorough clinical and radiological examinations as well as meticulous and prompt surgical resection. A 27-year-old male patient, who had been diagnosed with multiple osteochondromas and had never been operated on, presented with a one-year history of exercise-induced left calf pain, paresthesias of the left leg and pallor in cold weather. After radiographic and Computed Tomography angiographic evaluation, we diagnosed distal femur osteochondroma associated with an arterial compression of the left popliteal artery. A surgical treatment of all lesions was performed. No operative complications occurred. The pain was relieved. Good postoperative results have been noticed. Popliteal aretery entrapment syndrome may be caused by solitary or multiple osteochondromas around the knee. Therefore, prophylactic resection of exostoses in the surrounding area of a vessel should be performed. Moreover, the orthopedic surgeon should consider and prevent vascular complications during surgical resection of knee osteochondromas.


The Effect of Autologous Hamstring Graft Diameter on the Likelihood for Revision of Anterior Cruciate Ligament Reconstruction.
Hamstring autografts for anterior cruciate ligament (ACL) reconstruction (ACLR) have become popular in the past 2 decades; however, it is difficult to predict the diameter of the harvested tendons before surgery. Previous biomechanical studies have suggested that a smaller graft diameter leads to a lower load to failure, but clinical studies looking at various predictors for failure, including graft size, have been inconclusive. To evaluate the relationship of hamstring graft diameter to ACL revision within a large cohort of patients, while controlling for sex, age, body mass index (BMI), and femoral and tibial fixation type. Case-control study; Level of evidence, 3. A case-control study using patients registered in an ACLR registry was conducted. Revision was used as a marker for graft failure. A case was defined as a patient who underwent primary ACLR with a hamstring autograft that was revised during the study period (April 2006 to September 2012). Three controls, defined as patients who underwent primary ACLR with a hamstring autograft that was not revised, were matched to each of the cases according to age, sex, BMI, and femoral and tibial fixation type. Descriptive characteristics were employed, and conditional logistic regression was conducted to produce estimates of odds ratios and 95% CIs. A total of 124 cases and 367 controls were identified. There were no significant differences between cases and controls in the distribution of sex (52.4% male vs 52.9% male, respectively; P = .932), median age (17.6 years [interquartile range (IQR), 15.9-20.4] vs 17.6 years [IQR, 15.9-20.4], respectively; P = .999), median BMI (23.4 kg/m(2) [IQR, 21.5-26.4] vs 23.4 kg/m(2) [IQR, 21.6-25.8], respectively; P = .954), femoral fixation (P = .459), and tibial fixation (P = .766). The mean (±SD) graft diameter was 7.9 ± 0.75 mm in the cases and 8.1 ± 0.73 mm in the controls. The likelihood of a patient needing revision ACLR in the study cohort was 0.82 times lower (95% CI, 0.68-0.98) for every 0.5-mm increase in the graft diameter from 7.0 to 9.0 mm. In this study, within the range of 7.0 to 9.0 mm, there was a 0.82 times lower likelihood of being a revision case with every 0.5-mm incremental increase in graft diameter.


Vesicular stomatitis virus enables gene transfer and transsynaptic tracing in a wide range of organisms.
Current limitations in technology have prevented an extensive analysis of the connections among neurons, particularly within nonmammalian organisms. We developed a transsynaptic viral tracer originally for use in mice, and then tested its utility in a broader range of organisms. By engineering the vesicular stomatitis virus (VSV) to encode a fluorophore and either the rabies virus glycoprotein (RABV-G) or its own glycoprotein (VSV-G), we created viruses that can transsynaptically label neuronal circuits in either the retrograde or anterograde direction, respectively. The vectors were investigated for their utility as polysynaptic tracers of chicken and zebrafish visual pathways. They showed patterns of connectivity consistent with previously characterized visual system connections, and revealed several potentially novel connections. Further, these vectors were shown to infect neurons in several other vertebrates, including Old and New World monkeys, seahorses, axolotls, and Xenopus. They were also shown to infect two invertebrates, Drosophila melanogaster, and the box jellyfish, Tripedalia cystophora, a species previously intractable for gene transfer, although no clear evidence of transsynaptic spread was observed in these species. These vectors provide a starting point for transsynaptic tracing in most vertebrates, and are also excellent candidates for gene transfer in organisms that have been refractory to other methods.


Cats are not small dogs: is there an immunological explanation for why cats are less affected by arthropod-borne disease than dogs?
It is widely recognized that cats appear to be less frequently affected by arthropod-borne infectious diseases than dogs and share fewer zoonotic pathogens with man. This impression is supported by the relative lack of scientific publications related to feline vector-borne infections. This review explores the possible reasons for the difference between the two most common small companion animal species, including the hypothesis that cats might have a genetically-determined immunological resistance to arthropod vectors or the microparasites they transmit. A number of simple possibilities might account for the lower prevalence of these diseases in cats, including factors related to the lifestyle and behaviour of the cat, lesser spend on preventative healthcare for cats and reduced opportunities for research funding for these animals. The dog and cat have substantially similar immune system components, but differences in immune function might in part account for the markedly distinct prevalence and clinicopathological appearance of autoimmune, allergic, idiopathic inflammatory, immunodeficiency, neoplastic and infectious diseases in the two species. Cats have greater genetic diversity than dogs with much lower linkage disequilibrium in feline compared with canine breed groups. Immune function is intrinsically related to the nature of the intestinal microbiome and subtle differences between the canine and feline microbial populations might also impact on immune function and disease resistance. The reasons for the apparent lesser susceptibility of cats to arthropod-borne infectious diseases are likely to be complex, but warrant further investigation.


Biophotonic probing of macromolecular transformations during apoptosis.
We introduce here multiplex nonlinear optical imaging as a powerful tool for studying the molecular organization and its transformation in cellular processes, with the specific example of apoptosis. Apoptosis is a process of self-initiated cell death, critically important for physiological regulation and elimination of genetic disorders. Nonlinear optical microscopy, combining the coherent anti-Stokes Raman scattering (CARS) microscopy and two-photon excited fluorescence (TPEF), has been used for analysis of spatial distribution of major types of biomolecules: proteins, lipids, and nucleic acids in the cells while monitoring their changes during apoptosis. CARS imaging revealed that in the nuclei of proliferating cells, the proteins are distributed nearly uniformly, with local accumulations in several nuclear structures. We have found that this distribution is abruptly disrupted at the onset of apoptosis and is transformed to a progressively irregular pattern. Fluorescence recovery after photobleaching (FRAP) studies indicate that pronounced aggregation of proteins in the nucleoplasm of apoptotic cells coincides with a gradual reduction in their mobility.


[The creation of a "new" aorta and the characteristics of coronary artery transplantation in the anatomical correction of transposition of the great vessels of the heart].
Opinion varies among surgeons regarding the preferable method of surgical correction in patients with transposition of the great vessels (TGV) presenting with abnormal origins of the coronary artery (CA) and inadequacies in the diameters of the great vessels. In the work presented, the experience is analyzed gained with the performing of TGV radical correction operations of the arterial switch type in patients presenting with anomalous CA origins and abnormalities in diameters of the great vessels (n = 5). The submitted option permits simplifying CA transfer avoiding the coronary blood flow-related fatal intraoperative complications. Our modification of creation of a "new" aorta combined with particular features of implantation of the coronary arteries enabled us to secure good results in the presence of malformed, TGV, anatomy, which fact allowed the arterial switch operations to be extended to a greater number of cases in disadvantageous anatomical variants of TGV.


Evidence for physical and functional interactions among two Saccharomyces cerevisiae SH3 domain proteins, an adenylyl cyclase-associated protein and the actin cytoskeleton.
In a variety of organisms, a number of proteins associated with the cortical actin cytoskeleton contain SH3 domains, suggesting that these domains may provide the physical basis for functional interactions among structural and regulatory proteins in the actin cytoskeleton. We present evidence that SH3 domains mediate at least two independent functions of the Saccharomyces cerevisiae actin-binding protein Abp1p in vivo. Abp1p contains a single SH3 domain that has recently been shown to bind in vitro to the adenylyl cyclase-associated protein Srv2p. Immunofluorescence analysis of Srv2p subcellular localization in strains carrying mutations in either ABP1 or SRV2 reveals that the Abp1p SH3 domain mediates the normal association of Srv2p with the cortical actin cytoskeleton. We also show that a site in Abp1p itself is specifically bound by the SH3 domain of the actin-associated protein Rvs167p. Genetic analysis provides evidence that Abp1p and Rvs167p have functions that are closely interrelated. Abp1 null mutations, like rvs167 mutations, result in defects in sporulation and reduced viability under certain suboptimal growth conditions. In addition, mutations in ABP1 and RVS167 yield similar profiles of genetic "synthetic lethal" interactions when combined with mutations in genes encoding other cytoskeletal components. Mutations which specifically disrupt the SH3 domain-mediated interaction between Abp1p and Srv2p, however, show none of the shared phenotypes of abp1 and rvs167 mutations. We conclude that the Abp1p SH3 domain mediates the association of Srv2p with the cortical actin cytoskeleton, and that Abp1p performs a distinct function that is likely to involve binding by the Rvs167p SH3 domain. Overall, work presented here illustrates how SH3 domains can integrate the activities of multiple actin cytoskeleton proteins in response to varying environmental conditions.


Neurotoxicity of carbonyl sulfide in F344 rats following inhalation exposure for up to 12 weeks.
Carbonyl sulfide (COS), a high-priority Clean Air Act chemical, was evaluated for neurotoxicity in short-term studies. F344 rats were exposed to 75-600 ppm COS 6 h per day, 5 days per week for up to 12 weeks. In rats exposed to 500 or 600 ppm for up to 4 days, malacia and microgliosis were detected in numerous neuroanatomical regions of the brain by conventional optical microscopy and magnetic resonance microscopy (MRM). After a 2-week exposure to 400 ppm, rats were evaluated using a functional observational battery. Slight gait abnormality was detected in 50% of the rats and hypotonia was present in all rats exposed to COS. Decreases in motor activity, and forelimb and hindlimb grip strength were also detected. In rats exposed to 400 ppm for 12 weeks, predominant lesions were in the parietal cortex area 1 (necrosis) and posterior colliculus (neuronal loss, microgliosis, hemorrhage), and occasional necrosis was present in the putamen, thalamus, and anterior olivary nucleus. Carbonyl sulfide specifically targeted the auditory system including the olivary nucleus, nucleus of the lateral lemniscus, and posterior colliculus. Consistent with these findings were alterations in the amplitude of the brainstem auditory evoked responses (BAER) for peaks N3, P4, N4, and N5 that represented changes in auditory transmission between the anterior olivary nucleus to the medial geniculate nucleus in animals after exposure for 2 weeks to 400 ppm COS. A concentration-related decrease in cytochrome oxidase activity was detected in the posterior colliculus and parietal cortex of exposed rats as early as 3 weeks. Cytochrome oxidase activity was significantly decreased at COS concentrations that did not cause detectable lesions, suggesting that disruption of the mitochondrial respiratory chain may precede these brain lesions. Our studies demonstrate that this environmental air contaminant has the potential to cause a wide spectrum of brain lesions that are dependent on the degree and duration of exposure.


Range-adaptive standoff recognition of explosive fingerprints on solid surfaces using a supervised learning method and laser-induced breakdown spectroscopy.
The distance between the sensor and the target is a particularly critical factor for an issue as crucial as explosive residues recognition when a laser-assisted spectroscopic technique operates in a standoff configuration. Particularly for laser ablation, variations in operational range influence the induced plasmas as well as the sensitivity of their ensuing optical emissions, thereby confining the attributes used in sorting methods. Though efficient classification models based on optical emissions gathered under specific conditions have been developed, their successful performance on any variable information is limited. Hence, to test new information by a designed model, data must be acquired under operational conditions totally matching those used during modeling. Otherwise, the new expected scenario needs to be previously modeled. To facing both this restriction and this time-consuming mission, a novel strategy is proposed in this work. On the basis of machine learning methods, the strategy stems from a decision boundary function designed for a defined set of experimental conditions. Next, particular semisupervised models to the envisaged conditions are obtained adaptively on the basis of changes in laser fluence and light emission with variation of the sensor-to-target distance. Hence, the strategy requires only a little prior information, therefore ruling out the tedious and time-consuming process of modeling all the expected distant scenes. Residues of ordinary materials (olive oil, fuel oil, motor oils, gasoline, car wax and hand cream) hardly cause confusion in alerting the presence of an explosive (DNT, TNT, RDX, or PETN) when tested within a range from 30 to 50 m with varying laser irradiance between 8.2 and 1.3 GW cm(-2). With error rates of around 5%, the experimental assessments confirm that this semisupervised model suitably addresses the recognition of organic residues on aluminum surfaces under different operational conditions.


Pediatric prognostic models predicting inhospital child mortality in resource-limited settings: An external validation study.
Prognostic models provide evidence-based predictions and estimates of future outcomes, facilitating decision-making, patient care, and research. A few of these models have been externally validated, leading to uncertain reliability and generalizability. This study aims to externally validate four models to assess their transferability and usefulness in clinical practice. The models include the respiratory index of severity in children (RISC)-Malawi model and three other models by Lowlavaar et al. The study used data from the Clinical Information Network (CIN) to validate the four models where the primary outcome was in-hospital mortality. 163,329 patients met eligibility criteria. Missing data were imputed, and the logistic function was used to compute predicted risk of in-hospital mortality. Models' discriminatory ability and calibration were determined using area under the curve (AUC), calibration slope, and intercept. The RISC-Malawi model had 50,669 pneumonia patients who met the eligibility criteria, of which the case-fatality ratio was 4406 (8.7%). Its AUC was 0.77 (95% CI: 0.77-0.78), whereas the calibration slope was 1.04 (95% CI: 1.00 -1.06), and calibration intercept was 0.81 (95% CI: 0.77-0.84). Regarding the external validation of Lowlavaar et al. models, 10,782 eligible patients were included, with an in-hospital mortality rate of 5.3%. The primary model's AUC was 0.75 (95% CI: 0.72-0.77), the calibration slope was 0.78 (95% CI: 0.71-0.84), and the calibration intercept was 0.37 (95% CI: 0.28-0.46). All models markedly underestimated the risk of mortality. All externally validated models exhibited either underestimation or overestimation of the risk as judged from calibration statistics. Hence, applying these models with confidence in settings other than their original development context may not be advisable. Our findings strongly suggest the need for recalibrating these model to enhance their generalizability.


Reactivity to unpredictable threat as a treatment target for fear-based anxiety disorders.
Heightened reactivity to unpredictable threat (U-threat) is a core individual difference factor underlying fear-based psychopathology. Little is known, however, about whether reactivity to U-threat is a stable marker of fear-based psychopathology or if it is malleable to treatment. The aim of the current study was to address this question by examining differences in reactivity to U-threat within patients before and after 12-weeks of selective serotonin reuptake inhibitors (SSRIs) or cognitive-behavioral therapy (CBT). Participants included patients with principal fear (n = 22) and distress/misery disorders (n = 29), and a group of healthy controls (n = 21) assessed 12-weeks apart. A well-validated threat-of-shock task was used to probe reactivity to predictable (P-) and U-threat and startle eyeblink magnitude was recorded as an index of defensive responding. Across both assessments, individuals with fear-based disorders displayed greater startle magnitude to U-threat relative to healthy controls and distress/misery patients (who did not differ). From pre- to post-treatment, startle magnitude during U-threat decreased only within the fear patients who received CBT. Moreover, within fear patients, the magnitude of decline in startle to U-threat correlated with the magnitude of decline in fear symptoms. For the healthy controls, startle to U-threat across the two time points was highly reliable and stable. Together, these results indicate that startle to U-threat characterizes fear disorder patients and is malleable to treatment with CBT but not SSRIs within fear patients. Startle to U-threat may therefore reflect an objective, psychophysiological indicator of fear disorder status and CBT treatment response.


A systematic review of psychosocial interventions for family carers of palliative care patients.
Being a family carer to a patient nearing the end of their life is a challenging and confronting experience. Studies show that caregiving can have negative consequences on the health of family carers including fatigue, sleep problems, depression, anxiety and burnout. One of the goals of palliative care is to provide psychosocial support to patients and families facing terminal illness. A systematic review of interventions for family carers of cancer and palliative care patients conducted at the start of this millennium demonstrated that there was a dearth of rigorous inquiry on this topic and consequently limited knowledge regarding the types of interventions likely to be effective in meeting the complex needs of family carers. We wanted to discern whether or not the evidence base to support family carers has improved. Furthermore, undertaking this review was acknowledged as one of the priorities for the International Palliative Care Family Carer Research Collaboration http://www.centreforpallcare.org. A systematic review was undertaken in order to identify developments in family carer support that have occurred over the last decade. The focus of the review was on interventions that targeted improvements in the psychosocial support of family carers of palliative care patients. Studies were graded to assess their quality. A total of fourteen studies met the inclusion criteria. The focus of interventions included psycho-education, psychosocial support, carer coping, symptom management, sleep promotion and family meetings. Five studies were randomised controlled trials, three of which met the criteria for the highest quality evidence. There were two prospective studies, five pre-test/post-test projects and two qualitative studies. The systematic review identified a slight increase in the quality and quantity of psychosocial interventions conducted for family carers in the last decade. More rigorous intervention research is required in order to meet the supportive care needs of family carers of palliative care patients.


Steroid aerosols in asthma: an assessment of betamethasone valerate and a 12-month study of patients on maintenance treatment.
Betamethasone valerate aerosol is a new compound for the treatment of asthma. Its clinical effectiveness was established in a double-blind cross-over trial in non-steroid-dependent asthmatic patients. At a dosage of 400 to 800 mug/day for three months there was no evidence of suppression of hypothalamic-pituitary-adrenal function, as assessed by tetracosactrin and insulin stress tests.A 12-month follow-up study of 120 patients using steroid aerosols (betamethasone valerate or beclomethasone dipropionate) indicated that tolerance does not develop and that a daily maintenance dose of 200 mug/day was adequate in most patients. Temporary lack of response was observed during episodes of sputum production or of heavy exposure to antigen.There were no observed side effects other than fungal infections of the respiratory tract. However, the incidence of candidiasis of the pharynx (13%) and particularly of the larynx (5%) in apparently immunologically normal patients was disturbing. These infections were not seen in patients taking 200 mug/day. Though there is yet no evidence that fungal infections associated with steroid aerosols may penetrate the trachea and bronchi the possibility of this indicates that caution should be exercised in their use, particularly in long-term high dosage.


Meta-analysis of data from animal studies: a practical guide.
Meta-analyses of data from human studies are invaluable resources in the life sciences and the methods to conduct these are well documented. Similarly there are a number of benefits in conducting meta-analyses on data from animal studies; they can be used to inform clinical trial design, or to try and explain discrepancies between preclinical and clinical trial results. However there are inherit differences between animal and human studies and so applying the same techniques for the meta-analysis of preclinical data is not straightforward. For example preclinical studies are frequently small and there is often substantial heterogeneity between studies. This may have an impact on both the method of calculating an effect size and the method of pooling data. Here we describe a practical guide for the meta-analysis of data from animal studies including methods used to explore sources of heterogeneity.


Epidemiology and one-year outcomes in patients with chronic heart failure and preserved, mid-range and reduced ejection fraction: an analysis of the ESC Heart Failure Long-Term Registry.
The objectives of the present study were to describe epidemiology and outcomes in ambulatory heart failure (HF) patients stratified by left ventricular ejection fraction (LVEF) and to identify predictors for mortality at 1 year in each group. The European Society of Cardiology Heart Failure Long-Term Registry is a prospective, observational study collecting epidemiological information and 1-year follow-up data in 9134 HF patients. Patients were classified according to baseline LVEF into HF with reduced EF [EF <40% (HFrEF)], mid-range EF [EF 40-50% (HFmrEF)] and preserved EF [EF >50% (HFpEF)]. In comparison with HFpEF subjects, patients with HFrEF were younger (64 years vs. 69 years), more commonly male (78% vs. 52%), more likely to have an ischaemic aetiology (49% vs. 24%) and left bundle branch block (24% vs. 9%), but less likely to have hypertension (56% vs. 67%) or atrial fibrillation (18% vs. 32%). The HFmrEF group resembled the HFrEF group in some features, including age, gender and ischaemic aetiology, but had less left ventricular and atrial dilation. Mortality at 1 year differed significantly between HFrEF and HFpEF (8.8% vs. 6.3%); HFmrEF patients experienced intermediate rates (7.6%). Age, New York Heart Association (NYHA) class III/IV status and chronic kidney disease predicted mortality in all LVEF groups. Low systolic blood pressure and high heart rate were predictors for mortality in HFrEF and HFmrEF. A lower body mass index was independently associated with mortality in HFrEF and HFpEF patients. Atrial fibrillation predicted mortality in HFpEF patients. Heart failure patients stratified according to different categories of LVEF represent diverse phenotypes of demography, clinical presentation, aetiology and outcomes at 1 year. Differences in predictors for mortality might improve risk stratification and management goals.


Extranodal NK/T-Cell Lymphoma, Nasal Type, Extranasal and Ulcerative Blister Variant, Case Report.
The extranodal natural killer (NK) T-cell lymphoma of nasal type is a form of lymphoma that falls within the WHO/EORTC 2018 classification of cutaneous T-cell lymphomas. It is characterized for being aggressive, infrequent, and destroying midline facial structures; however, it can also be in primary or secondary form at extranasal sites, such as the skin or the gastrointestinal tract, among others. We report the case of an 18-year-old patient with an extranodal NK/T-cell lymphoma located in an extranasal site. The clinical presentation is characterized for being multifocal and with erythematous-violaceous plaques that progress to hemorrhagic blisters and necrotic ulcers. Although this type of lymphoma has been reported previously by others, the presence of blisters is an atypical finding, which we believe has been described only in one case in the medical literature.


A mouse bleeding model to study oral anticoagulants.
New oral anticoagulants to reduce the incidence of thrombosis have recently become available. When compared to the existing therapy, warfarin, these novel agents have similar efficacy with a reduced risk of spontaneous bleeding. However, these novel agents have been associated with significant, even fatal, bleeding following trauma. Reversal agents are being developed that bind and neutralize these oral anticoagulants. However, these are not yet available. Another strategy is to increase thrombin generation by administration of "bypassing" agents such as prothrombin complex concentrates or factor VIIa. Several animal models have been used to model the hemostatic defect induced by the thrombin inhibitor dabigatran. A rat tail injury model, a rabbit cuticle bleeding model, and a rabbit kidney laceration model have all been reported to show increased bleeding, but with supratherapeutic doses of dabigatran. A mouse tail transection model has been reported to reflect increased bleeding at peak therapeutic dabigatran levels. We found that the Whinna saphenous vein hemostasis model reliably reflects a hemostatic defect at therapeutic levels of dabigatran. This model can potentially reflect the effects of reversal or bypassing agents.


Sustainability of meat-based and plant-based diets and the environment.
Worldwide, an estimated 2 billion people live primarily on a meat-based diet, while an estimated 4 billion live primarily on a plant-based diet. The US food production system uses about 50% of the total US land area, 80% of the fresh water, and 17% of the fossil energy used in the country. The heavy dependence on fossil energy suggests that the US food system, whether meat-based or plant-based, is not sustainable. The use of land and energy resources devoted to an average meat-based diet compared with a lactoovovegetarian (plant-based) diet is analyzed in this report. In both diets, the daily quantity of calories consumed are kept constant at about 3533 kcal per person. The meat-based food system requires more energy, land, and water resources than the lactoovovegetarian diet. In this limited sense, the lactoovovegetarian diet is more sustainable than the average American meat-based diet.


[Genetic toxicity of methylmercuric chloride (CH3HgCl) on mitochondria of Saccharomyces cerevisiae].
Among the strains of the yeast Saccharomyces cerevisiae we investigated, the organic form of mercury:methylmercury (II) does not seem to induce any cytoplasmic mutant "petite colonie" rho-. However, it induces a significant number of the erythromycin-resistant mutant Eryr. A dose response is shown. These effects are discussed in the view of the part that discrete DNA lesions could take in the explanation of the mechanism of toxicity of the organomercurial.


BOARD-INVITED REVIEW: Quantifying water use in ruminant production.
The depletion of water resources, in terms of both quantity and quality, has become a major concern both locally and globally. Ruminants, in particular, are under increased public scrutiny due to their relatively high water use per unit of meat or milk produced. Estimating the water footprint of livestock production is a relatively new field of research for which methods are still evolving. This review describes the approaches used to quantify water use in ruminant production systems as well as the methodological and conceptual issues associated with each approach. Water use estimates for the main products from ruminant production systems are also presented, along with possible management strategies to reduce water use. In the past, quantifying water withdrawal in ruminant production focused on the water demand for drinking or operational purposes. Recently, the recognition of water as a scarce resource has led to the development of several methodologies including water footprint assessment, life cycle assessment, and livestock water productivity to assess water use and its environmental impacts. These methods differ with respect to their target outcome (efficiency or environmental impacts), geographic focus (local or global), description of water sources (green, blue, and gray), handling of water quality concerns, the interpretation of environmental impacts, and the metric by which results are communicated (volumetric units or impact equivalents). Ruminant production is a complex activity where animals are often reared at different sites using a range of resources over their lifetime. Additional water use occurs during slaughter, product processing, and packaging. Estimating water use at the various stages of meat and milk production and communicating those estimates will help producers and other stakeholders identify hotspots and implement strategies to improve water use efficiency. Improvements in ruminant productivity (i.e., BW and milk production) and reproductive efficiency can also reduce the water footprint per unit product. However, given that feed production makes up the majority of water use by ruminants, research and development efforts should focus on this area. More research and clarity are needed to examine the validity of assumptions and possible trade-offs between ruminants' water use and other sustainability indicators.


Physical fitness training for stroke patients.
Levels of physical fitness are low after stroke. It is unknown whether improving physical fitness after stroke reduces disability. To determine whether fitness training after stroke reduces death, dependence, and disability. The secondary aims were to determine the effects of training on physical fitness, mobility, physical function, quality of life, mood, and incidence of adverse events. We searched the Cochrane Stroke Group Trials Register (last searched April 2010), the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library, July 2010), MEDLINE (1966 to March 2010), EMBASE (1980 to March 2010), CINAHL (1982 to March 2010), SPORTDiscus (1949 to March 2010), and five additional databases (March 2010). We also searched ongoing trials registers, handsearched relevant journals and conference proceedings, screened reference lists, and contacted experts in the field. Randomised trials comparing either cardiorespiratory training or resistance training, or both, with no intervention, a non-exercise intervention, or usual care in stroke survivors. Two review authors independently selected trials, assessed quality, and extracted data. We analysed data using random-effects meta-analyses. Diverse outcome measures limited the intended analyses. We included 32 trials, involving 1414 participants, which comprised cardiorespiratory (14 trials, 651 participants), resistance (seven trials, 246 participants), and mixed training interventions (11 trials, 517 participants). Five deaths were reported at the end of the intervention and nine at the end of follow-up. No dependence data were reported. Diverse outcome measures made data pooling difficult. The majority of the estimates of effect were not significant. Cardiorespiratory training involving walking improved maximum walking speed (mean difference (MD) 8.66 metres per minute, 95% confidence interval (CI) 2.98 to 14.34), preferred gait speed (MD 4.68 metres per minute, 95% CI 1.40 to 7.96) and walking capacity (MD 47.13 metres per six minutes, 95% CI 19.39 to 74.88) at the end of the intervention. These training effects were retained at the end of follow-up. Mixed training, involving walking, increased preferred walking speed (MD 2.93 metres per minute, 95% CI 0.02 to 5.84) and walking capacity (MD 30.59 metres per six minutes, 95% CI 8.90 to 52.28) but effects were smaller and there was heterogeneity amongst the trial results. There were insufficient data to assess the effects of resistance training. The variability in the quality of included trials hampered the reliability and generalizability of the observed results. The effects of training on death, dependence, and disability after stroke are unclear. There is sufficient evidence to incorporate cardiorespiratory training involving walking within post-stroke rehabilitation programmes to improve speed, tolerance, and independence during walking. Further well-designed trials are needed to determine the optimal exercise prescription and identify long-term benefits.


Fine-needle aspiration cytology of thyroid nodules with Hürthle cells: cytomorphologic predictors for neoplasms, improving diagnostic accuracy and overcoming pitfalls.
Hürthle cells (HCs) are follicular-derived oncocytic cells seen in a variety of neoplastic and nonneoplastic pathologic entities of the thyroid gland. This study was to report our experience of the surgical outcome on the finding of HCs on fine-needle aspiration biopsies (FNABs) of thyroid nodules, to identify cytologic predictors of HC neoplasms and an attempt to overcome diagnostic pitfalls. This was a retrospective study of all FNAB of thyroid nodules with findings of HCs with subsequent surgical resection. The FNAB slides of 70 thyroid nodules were blindly reviewed for specific cytomorphologic characteristics. The cytologic findings were correlated with the corresponding final surgical pathology diagnosis. The patients ranged in age from 25 to 78 years with a male:female ratio of 1:2. There were 19 false-negative and 4 false-positive cases. Overall high cellularity, scant colloid and >90% HCs on FNAB are consistently seen in a neoplastic HC process. All cases of Hashimoto's thyroiditis were associated with prominent nucleoli and 92% of cases demonstrating transgressing vessels were neoplastic. Diagnostic accuracy can be improved by following the current Bethesda classification system. A constellation of cytomorphologic features in conjunction with clinical findings can be considered a strong predictor of a neoplastic process.


Open versus minimally invasive surgical approaches in pediatric urology: Trends in utilization and complications.
Minimally invasive surgery (MIS) techniques are anecdotally reported to be increasingly used, but little objective data supports this. Our objective was to assess trends in MIS utilization across various procedures in pediatric urology and to compare postoperative complication rates between MIS and open procedures. We analyzed the 1998-2012 Nationwide Inpatient Sample. We identified children (<18 years old) undergoing open and MIS inpatient procedures and any in-hospital post-operative complications that occurred during that postoperative hospitalization. We utilized propensity score matching and multivariable logistic regression to adjust for confounding factors. We identified 163,838 weighted encounters in the "overall cohort," 70,273 of which were at centers performing more than five MIS procedures over the years studied. Use of MIS techniques increased significantly over time for several procedures, most prominently for nephrectomy (Fig.). The overall rate of complications was lower in patients undergoing MIS compared with open surgery (6% vs. 11%, p < 0.001). Specialized centers had a significantly lower overall rate of complications than unspecialized centers (9% vs. 12%, p < 0.001). Within specialized centers, MIS had lower complication rates than open procedures (7% vs. 9%, p < 0.001); this finding was consistent even after adjusting for other factors (OR 0.71, p = 0.02). Limitations include that these data may not be generalizable to encounters not in the sample pool. As a large, retrospective, administrative database, NIS may be affected by miscoding bias - rendering our analysis sensitive to the accuracy of procedure coding in NIS. Although the accuracy level of NIS is high for an administrative database, it is possible at least some portion of our cohort may be incorrectly coded. Further, the NSQIP complications we identified may represent associated comorbidities and not true postoperative complications, as NIS does not provide temporal relationships between different diagnosis codes. Despite these limitations, we note that the NIS database is rigorously monitored and audited for coding accuracy and, therefore, represents a reasonably reliable panorama of the characteristics of an inpatient surgical cohort. However, it is important to note that the choice of operative modality is, undoubtedly, multifactorial and patient/setting-specific. There is increasing use of MIS for pediatric urology procedures, although utilization rates vary among procedures. MIS was associated with a lower postoperative complication rate than for open procedures. Higher-volume MIS centers have a lower complication rate than lower-volume centers.


A methodology for building culture and gender norms into intervention: an example from Mumbai, India.
This paper responds to the call for culturally-relevant intervention research by introducing a methodology for identifying community norms and resources in order to more effectively implement sustainable interventions strategies. Results of an analysis of community norms, specifically attitudes toward gender equity, are presented from an HIV/STI research and intervention project in a low-income community in Mumbai, India (2008-2012). Community gender norms were explored because of their relevance to sexual risk in settings characterized by high levels of gender inequity. This paper recommends approaches that interventionists and social scientists can take to incorporate cultural insights into formative assessments and project implementation These approaches include how to (1) examine modal beliefs and norms and any patterned variation within the community; (2) identify and assess variation in cultural beliefs and norms among community members (including leaders, social workers, members of civil society and the religious sector); and (3) identify differential needs among sectors of the community and key types of individuals best suited to help formulate and disseminate culturally-relevant intervention messages. Using a multi-method approach that includes the progressive translation of qualitative interviews into a quantitative survey of cultural norms, along with an analysis of community consensus, we outline a means for measuring variation in cultural expectations and beliefs about gender relations in an urban community in Mumbai. Results illustrate how intervention strategies and implementation can benefit from an organic (versus a priori and/or stereotypical) approach to cultural characteristics and analysis of community resources and vulnerabilities.


Compressive hyperspectral microscopy for cancer detection.
Hyperspectral microscopy grants the ability to characterize unique properties of tissues based on their spectral fingerprint. The ability to label and measure multiple molecular probes simultaneously provides pathologists and oncologists with a powerful tool to enhance accurate diagnostic and prognostic decisions. As the pathological workload grows, having an objective tool that provides companion diagnostics is of immense importance. Therefore, fast whole-slide spectral imaging systems are of immense importance for automated cancer prognostics that meet current and future needs. We aim to develop a fast and accurate hyperspectral microscopy system that can be easily integrated with existing microscopes and provide flexibility for optimizing measurement time versus spectral resolution. The method employs compressive sensing (CS) and a spectrally encoded illumination device integrated into the illumination path of a standard microscope. The spectral encoding is obtained using a compact liquid crystal cell that is operated in a fast mode. It provides time-efficient measurements of the spectral information, is modular and versatile, and can also be used for other applications that require rapid acquisition of hyperspectral images. We demonstrated the acquisition of breast cancer biopsies hyperspectral data of the whole camera area within ∼1 s. This means that a typical 1×1 cm2 biopsy can be measured in ∼10 min. The hyperspectral images with 250 spectral bands are reconstructed from 47 spectrally encoded images in the spectral range of 450 to 700 nm. CS hyperspectral microscopy was successfully demonstrated on a common lab microscope for measuring biopsies stained with the most common stains, such as hematoxylin and eosin. The high spectral resolution demonstrated here in a rather short time indicates the ability to use it further for coping with the highly demanding needs of pathological diagnostics, both for cancer diagnostics and prognostics.


Gaze-probe joint guidance with multi-task learning in obstetric ultrasound scanning.
In this work, we exploit multi-task learning to jointly predict the two decision-making processes of gaze movement and probe manipulation that an experienced sonographer would perform in routine obstetric scanning. A multimodal guidance framework, Multimodal-GuideNet, is proposed to detect the causal relationship between a real-world ultrasound video signal, synchronized gaze, and probe motion. The association between the multi-modality inputs is learned and shared through a modality-aware spatial graph that leverages useful cross-modal dependencies. By estimating the probability distribution of probe and gaze movements in real scans, the predicted guidance signals also allow inter- and intra-sonographer variations and avoid a fixed scanning path. We validate the new multi-modality approach on three types of obstetric scanning examinations, and the result consistently outperforms single-task learning under various guidance policies. To simulate sonographer's attention on multi-structure images, we also explore multi-step estimation in gaze guidance, and its visual results show that the prediction allows multiple gaze centers that are substantially aligned with underlying anatomical structures.


Comorbidity Profiles and Their Effect on Treatment Selection and Survival among Patients with Lung Cancer.
Prior work has shown that the comorbidity burden is high among patients with lung cancer, but patterns of comorbid conditions have not been systematically identified. We aimed to identify distinct comorbidity profiles in a large sample of patients with lung cancer and to examine the effect of comorbidity profiles on treatment and survival. In this retrospective cohort study, we used latent class analysis to identify comorbidity profiles (or classes) in a population-based sample of 6,662 patients with bronchogenic carcinoma diagnosed between 2008 and 2013. We included specific comorbid conditions from the Charlson comorbidity index. We used Cox proportional hazards analysis to examine the effect of comorbidity class on survival. The mean age of the patients was 70 years, and 50% were female, 34% were nonwhite, and 17% were never-smokers. Most patients had stage III (21%) or IV (53%) disease. Over half (51%) had at least one comorbid condition, whereas 18% had at least four comorbidities. Latent class analysis identified five distinct comorbidity classes. Classes were defined by progressively greater Charlson comorbidity index scores and were further distinguished by the presence or absence of specific types of vascular disease and diabetes. Comorbidity class was independently associated with treatment selection (P < 0.001) and survival (P < 0.0001), especially among patients with stages 0-II disease (P < 0.0001). Patients with lung cancer can be described by distinct comorbidity profiles that are independent predictors of treatment and survival. These profiles provide a more nuanced understanding of how comorbidities cluster within patients with lung cancer and how they can be applied for descriptive purposes or in research.


Entering the era of targeted therapy for chronic lymphocytic leukemia: impact on the practicing clinician.
Chemoimmunotherapy has been the standard of care for chronic lymphocytic leukemia (CLL). However, the introduction of B-cell receptor (BCR) kinase inhibitors such as ibrutinib has the potential to eliminate the role of chemotherapy in the treatment of CLL. How to best incorporate old and new therapies for CLL in this landscape is increasingly complex. This article reviews current data available to clinicians and integrates these data to provide a strategy that can be used to approach the treatment of CLL in the era of BCR signaling inhibitors. Current strategies separate patients based on age or functional status as well as genetics [presence or absence of del(17)(p13.1)]. In the era of targeted therapy, this will likely continue based on current available data. Phase III studies support chemoimmunotherapy as the initial standard therapy for patients without del(17)(p13.1). Choice of chemotherapy (fludarabine plus cyclophosphamide, bendamustine, or chlorambucil) and anti-CD20 antibody (rituximab, ofatumumab, or obinutuzumab) varies based on regimen and patient status. For patients with del(17)(p13.1), no standard initial therapy exists, although several options supported by phase II clinical trials (methylprednisolone plus alemtuzumab or ibrutinib) seem better than chemoimmunotherapy. Treatment of relapsed CLL seems to be best supported by ibrutinib-based therapy. Completion of trials with ibrutinib and other new agents in the near future will offer opportunity for chemotherapy-free treatment across all groups of CLL. Therapy for CLL has evolved significantly over the past decade with introduction of targeted therapy for CLL. This has the potential to completely transform how CLL is treated in the future.


A preliminary screening of potentially antimalarial plants against Plasmodium falciparum in vitro.
Plasmodium is a blood protozoan parasite that is responsible for malaria. To date, Plasmodium falciparum has shown multi-drug resistance, particularly in Thailand, Myanmar and Malaysia. The aim of the study is to screen the plant extracts that can effectively inhibit P. falciparum 3D7, a common lab strain malaria parasite. Nine plants were collected and processed through maceration using hexane, chloroform and ethanol, resulting in 24 crude plant extracts. Of these, extracts from Artabotrys crassifolius, Pericampylus glacus and Leuconotis eugeniifolia showed promising antiplasmodial activities at IC50 of 15.32 to 39.75 µg/mL in a modified schizont maturation assay. Further studies are warranted to explore its efficacies and lead compounds of these three plant extracts for the development of antiplasmodial drugs.