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A rationalization of the alternative crystal structures adopted by a given molecular compound or by a set of substitutionally related molecular compounds is provided by reference to the five known polymorphs of sulfathiazole and 16 substituted 2-benzyl-5-benzylidene cyclopentanones (BBCPs), respectively. Two-dimensional (2D) packing fractions (ϕ 2D ) take space-group symmetry into account, with a clear demarcation of closed-packed zones (CPZ) and molecular junction zones (JZ) in all Z' = 1 structures. Representation of the molecules as two linked rods allows a concise treatment of conformation and rapid visualization of crystal packing. Combined with calculations of intermolecular potential energies, the rod method provides insight into the stabilization mechanisms of alternative polymorphs. In sulfathiazole, the primary factor is to obtain satisfactory hydrogen bonding, with close packing a secondary consideration. In BBCP derivatives, by comparison, close packing is the primary mechanism of stabilization. Whereas the 2D structures arising in CPZ can be analysed as tessellations of molecular-based cells, a method based on 2D Dirichlet cells is required for the JZ. These are calculated from the centroids of the molecular envelopes in high-symmetry planes. It is shown that these centroid coordinates, when combined with space-group symmetry and unit cell coordinates, provide a concise parameterization of all structures containing JZ. It is anticipated that this parameterization may be exploited to predict such crystal structures from powder diffraction data.

Purpose: To compare maternal and neonatal outcomes following the development of a multidisciplinary care team for the management of pregnancies complicated by placenta accreta spectrum (PAS) in a rural state., Methods: This is a retrospective cohort study evaluating pregnancies managed before PAS team care management formation (2010-2015) and after (2016-2020) in a university medical center. Maternal and neonatal outcomes were analyzed. Patients were grouped by delivery date to either before or after dedicated PAS team formation. Maternal and neonatal outcomes were analyzed. Frequencies and percentages were reported for categorical measures while means and standard deviations were computed for continuous measures. Wilcoxon rank-sum test was used for continuous variables while Chi-square or Fisher's exact was used for categorical measures., Findings: There were 82 patients with PAS managed at our institution (29 in Pre-PAS team group and 53 in Post-PAS team group). The number of units of packed red blood cells (PRBCS) transfused intraoperatively was significantly higher in the Pre-PAS care team group (6.52 vs. 3.26, p  = .0057). The total number of units PRBCS transfused (9.93 vs. 3.51, p  = .0014) and total number of cryoprecipitate transfused (0.77 vs. 0.08, p  = .0225) during the entire hospital stay were increased in the Pre-PAS team group. Median neonatal 1 min and 5 min APGAR scores were lower in the Pre-PAS care team group (2 vs 6 at 1 min, p  = .0035; 6 vs. 7at 5 min, p  = .0301)., Conclusions: Management of PAS by a dedicated, multidisciplinary team results in less blood transfusion requirements and improved maternal and neonatal outcomes.

Background: Utilization of simulation training in medical education has increased over time, particularly for less common scenarios and procedures. Simulation allows trainees to practice in a low-stress environment and eliminates patient risk. Cerclage placement has become less frequent, which limits obstetrics and gynecology (OB/GYN) exposure to cerclage placement during training. This exposes an area of training requiring simulation in OB/GYN resident education., Objective: To evaluate resident reception to cerclage simulation, their self-reported comfort with and ability to troubleshoot difficult cerclage placement immediately and 12 months following didactic education and simulation., Methods: In 2019, 18/20 (90%) OB/GYN residents in our university program underwent didactic teaching and simulation in cerclage placement using a pelvic model with removable cervix. Residents completed a survey immediately and 12 months following simulation. Wilcoxon signed-rank test was used to analyze resident self-report of comfort with cerclage placement and skill techniques for navigating difficult placement before and after simulation training. Descriptive statistics were analyzed as means and standard deviations., Results: Eighteen of twenty (90%) residents participated in the education session in cerclage placement. All 18 (100%) completed a postsimulation survey and 17/18 (94%) completed a survey 12 months later. All reported improved comfort with cerclage placement and statistically significant improvement in knowledge on techniques for troubleshooting difficult placement after simulation. All residents reported that the simulation enhanced their learning and recommended the simulation for future educational opportunities., Conclusions: Cerclage simulation was well-received by OB/GYN residents in learning and practicing cerclage placement. Residents demonstrated improved comfort with placement following simulation.

Objective: To compare prophylactic and emergent resuscitative endovascular balloon occlusion of the aorta (REBOA) catheter placement in the management of placenta accreta spectrum (PAS)., Study Design: Retrospective chart review of all patients with PAS (January 2018 to January 2020) at a single tertiary center who underwent prophylactic or emergent REBOA for cesarean hysterectomy for PAS., Results: A total of 16 pregnant patients with PAS underwent percutaneous REBOA placement by acute care surgeons in collaboration with a multi-disciplinary PAS team. The REBOA catheter was placed prophylactically in 11 cases and emergently in 5 cases. No complications occurred in the prophylactic placement group. In the emergent placement group, 3 of 4 surviving patients had vascular access site complications requiring intervention., Conclusion: A multidisciplinary approach for the management of PAS utilizing REBOA is feasible in the setting of both planned and emergent cesarean hysterectomy and can aid in the control of acute hemorrhage. The risk for vascular access site complications related to REBOA catheter placement is higher in the emergent setting compared to prophylactic placement.

Objective: There is limited data on the treatment of coronavirus disease 2019 (COVID-19) in pregnancy. Arkansas saw an increase in COVID-19 cases in June 2020. The first critically ill pregnant patient was admitted to our institution on May 21 st , 2020. The objective of this study was to evaluate outcomes in critically ill pregnant women with COVID-19 at a single tertiary care center who received remdesivir and convalescent plasma (CCP)., Study Design: This is a retrospective observational review of critically ill pregnant women with COVID-19 who received remdesivir and CCP. This study was approved by the institutional review board (#261354)., Results: Seven pregnant patients with COVID-19 were admitted to the intensive care unit (ICU). All received remdesivir and CCP. Six received dexamethasone. The median ICU length of stay (LOS) was 8 days (range 3-17). Patient 1 had multi-organ failure requiring vasopressors, renal dialysis, and had an intrauterine fetal demise. Patients 4 and 6 required mechanical ventilation, were delivered for respiratory distress and were extubated at 2 and 1 days postpartum, respectively. The only common risk factor was obesity. There were no adverse events noted with remdesivir or CCP., Conclusion: There is little data regarding the use of remdesivir or CCP for the treatment of COVID-19 in pregnant women. In our cohort, these were well tolerated with no adverse events. Previously reported median ICU LOS in critically ill pregnant women with COVID-19 was 8 days (range 4-15).1 Our study found a similar ICU LOS (8 days; range 3-17). Patient 1 did not receive remdesivir or CCP until transport to our facility on hospital day 3. Excluding patient 1, median ICU LOS was 6.5 days (range 3-9). Our institution's treatment of pregnant women with critical illness with remdesivir, CCP and dexamethasone combined with delivery in select cases has thus far had good outcomes., Key Points: · Combined therapy: remdesivir, CCP, dexamethasone.. · Remdesivir, CCP and dexamethasone was effective in treating critically ill pregnant women with COVID-19.. · No adverse events were associated with combined therapy.. · Delivery improved respiratory status.., Competing Interests: None declared., (Thieme. All rights reserved.)

Objective: To determine the accuracy and reliability of remotely directed and interpreted ultrasound (teleultrasound) as compared with standard in-person ultrasound for the detection of fetal anomalies, and to determine participants' satisfaction with teleultrasound., Study Design: This was a single-center, randomized (1:1) noninferiority study. Individuals referred to the maternal-fetal medicine (MFM) ultrasound clinic were randomized to standard in-person ultrasound and counseling or teleultrasound and telemedicine counseling. The primary outcome was major fetal anomaly detection rate (sensitivity). All ultrasounds were performed by registered diagnostic medical sonographers and interpretations were done by a group of five MFM physicians. After teleultrasound was completed, the teleultrasound patients filled out a satisfaction survey using a Likert scale. Newborn data were obtained from the newborn record and statewide birth defect databases., Results: Of 300 individuals randomized in each group, 294 were analyzed in the remotely interpreted teleultrasound group and 291 were analyzed in the in-person ultrasound group. The sensitivity of sonographic detection of 28 anomalies was 82.14% in the control group and of 20 anomalies in the telemedicine group, it was 85.0%. The observed difference in sensitivity was 0.0286, much smaller than the proposed noninferiority limit of 0.05. Specificity, negative predictive value, positive predictive value, and accuracy were more than 94% for both groups. Patient satisfaction was more than 95% on all measures, and there were no significant differences in patient satisfaction based on maternal characteristics., Conclusion: Teleultrasound is not inferior to standard in-person ultrasound for the detection of fetal anomalies. Teleultrasound was uniformly well received by patients, regardless of demographics. These key findings support the continued expansion of telemedicine services., Key Points: · For detection of major anomalies, teleultrasound is comparable to standard ultrasound.. · Teleultrasound was well accepted by patients.. · Teleultrasound use should be expanded.., Competing Interests: None declared., (Thieme. All rights reserved.)

Importance: As assisted reproductive technology has advanced, there has been an increase in gestational carriers/surrogate pregnancies. Information is needed to determine if these pregnancies are high-risk pregnancies and should be managed by maternal fetal medicine or if they are not high risk and should be cared for by residency-trained obstetricians and gynecologists., Objective: In this review of the literature, we explore whether surrogate pregnancies should be classified as high-risk pregnancies and managed by subspecialists., Evidence Acquisition, Results: Our literature search discovered 28 relevant studies that evaluated surrogate pregnancy and pregnancy complications/outcomes. We learned that the overall risk by using artificial reproductive technology and risks for hypertension, preterm delivery, cesarean delivery, low birth weight neonate, fetal anomalies, and stillbirth did not seem to increase maternal/perinatal risk to the level where a subspecialist was required for the inclusive management of a gestational surrogate. Given that the ideal gestational carrier is healthy, has previously had a term pregnancy, has a single embryo implanted, and has had no more than 3 prior cesarean deliveries, these pregnancies should be lower-risk pregnancies., Conclusions: We recommend that close monitoring and high index of suspicion should be maintained for complications, but care for the surrogate pregnancy can be accomplished by a residency-trained obstetrician-gynecologist., Relevance: An uncomplicated surrogate pregnancy can be managed by a residency-trained obstetrician-gynecologist and does not need to be managed by high-risk obstetric subspecialists.

Background: Guidelines recommend increased salt intake as a first-line recommendation in the management of symptomatic orthostatic hypotension and recurrent syncope. There have been no systematic reviews of this intervention. We sought to summarize the evidence for increased salt intake in patients with orthostatic intolerance syndromes., Methods: We conducted a systematic review and meta-analysis of studies in PubMed, EMBASE, and CINAHL. Interventional studies that increased salt intake in individuals with orthostatic intolerance syndromes were included. Primary outcome measures included incidence of falls and injuries, and rates of syncope and presyncope. Secondary outcome measures included other orthostatic intolerance symptoms, blood pressure, and heart rate., Results: A total of 14 studies were eligible, including participants with orthostatic hypotension, syncope, postural orthostatic tachycardia syndrome, and idiopathic orthostatic tachycardia (n = 391). Mean age was 35.6 (± 15) years. All studies were small and short-term (<60 mins-90 days). No study reported on the effect of increased salt intake on falls or injuries. Meta-analysis demonstrated that during head-up tilt, mean time to presyncope with salt intake increased by 1.57 minutes (95% confidence interval [CI], 1.26-1.88), mean systolic blood pressure increased by 12.27 mm Hg (95% CI, 10.86-13.68), and mean heart rate decreased by -3.97 beats per minute (95% CI, -4.08 to -3.86), compared with control. Increased salt increased supine blood pressure by 1.03 mm Hg (95% CI, 0.81 to 1.25). Increased salt intake resulted in an improvement or resolution of symptoms in 62.3% (95% CI, 51.6 to 72.6) of participants in short-term follow-up studies (mean follow-up of 44.3 days, 6 studies; n=91). Methodological quality of studies were low with high statistical heterogeneity in all meta-analyses., Conclusions: Our meta-analysis provides low-quality evidence of a short-term improvement in orthostatic intolerance with increased salt intake. There were no clinical trials demonstrating the efficacy and safety of increased salt intake on long-term clinical outcomes. Overall, there is a paucity of clinical trial evidence to support a cornerstone recommendation in the management of orthostatic intolerance syndromes., (Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)

Objectives: To identify abnormal amniotic fluid volumes (AFVs), normal volumes must be determined. Multiple statistical methods are used to define normal amniotic fluid curves; however, quantile regression (QR) is gaining favor. We reanalyzed ultrasound estimates in identifying oligohydramnios, normal fluid, and polyhydramnios using normal volumes calculated by QR., Methods: Data from 506 dye-determined or directly measured AFVs along with ultrasound estimates were analyzed. Each was classified as low, normal, or high for both the single deepest pocket (SDP) and amniotic fluid index (AFI). A weighted κ statistic was used to assess the level of agreement between the AFI and SDP compared to actual AFVs by QR., Results: The overall level of agreement for the AFI was fair (κ = 0.26), and that for the SDP was slight (κ = 0.19). Although not statistically significant (P = .792), the positive predictive value to classify a low volume using the AFI was lower compared to the SDP (35% vs 43%). The positive predictive value for a high volume was higher using the AFI compared to the SDP (55% versus 31%) but not statistically significant. The missed-call rate for high-volume identification by the SDP versus AFI was statistically significant (odds ratio, 5.5; 95% confidence interval, 2.04-14.97). The missed-call rate for low-volume identification by the AFI versus SDP was not statistically significant (odds ratio, 3.3; 95% confidence interval, 0.96-11.53)., Conclusions: Both the AFI and SDP identify actual normal AFVs by QR, with sensitivity higher than 90%. The SDP is superior for identification of oligohydramnios, and the AFI superior for identification of polyhydramnios., (© 2019 by the American Institute of Ultrasound in Medicine.)

Objective: This study sought to determine whether there is a significant difference in amniotic fluid measurements when measuring perpendicular to the floor compared with perpendicular to the uterine contour using both amniotic fluid index and single deepest pocket., Methods: This was a single-centre, prospective study of women with singleton gestation who were undergoing fetal ultrasound examination. A total of 240 women were enrolled, and single deepest pocket and amniotic fluid index were measured with both techniques. Correlation coefficient and intraclass correlation coefficient were used to assess the agreement between the values using the two methods of measurement (Canadian Task Force Classification II-2)., Results: A strong correlation was found between amniotic fluid index measurements (correlation coefficient 0.82; intraclass correlation coefficient 0.7). A strong correlation also was found between single deepest pocket measurements (correlation coefficient 0.7; intraclass correlation coefficient 0.6)., Conclusion: The measurement of amniotic fluid index and single deepest pocket can be performed either perpendicular to the floor or perpendicular to the uterine contour. There is no significant difference between these measurements and they correlate well., (Copyright © 2019. Published by Elsevier Inc.)

Pharmaceutical salt solvates (dimethyl sulfoxide, DMSO) of the drug triamterene with the coformers acetic, succinic, adipic, pimelic, azelaic and nicotinic acid and ibuprofen are prepared by liquid-assisted grinding and solvent-evaporative crystallization. The modified Δp K a rule as proposed by Cruz-Cabeza [(2012 ▸). CrystEngComm , 14 , 6362-6365] is in close agreement with the results of this study. All adducts were characterized by X-ray diffraction and thermal analytical techniques, including single-crystal X-ray diffraction, powder X-ray diffraction, differential scanning calorimetry and thermal gravimetric analysis. Hydrogen-bonded motifs combined to form a variety of extended tapes and sheets. Analysis of the crystal structures showed that all adducts existed as salt solvates and contained the amino-pyridinium-carboxyl-ate heterodimer, except for the solvate containing triamterene, ibuprofen and DMSO, as a result of the presence of a strong and stable hemitriamterenium duplex. A search of the Cambridge Structural Database (CSD 5.36, Version 1.18) to determine the frequency of occurrence of the putative supramolecular synthons found in this study showed good agreement with previous work.

Objectives: To determine whether color Doppler sonography increases the detection of pregnancies at risk for adverse outcomes., Methods: Participants admitted to labor and delivery with the anticipation of a vaginal delivery underwent measurements of amniotic fluid volume (AFV) using amniotic fluid index (AFI) and single deepest pocket (SDP) techniques by grayscale followed by color Doppler sonography. Oligohydramnios was defined as an AFI of less than 5 cm or an SDP of less than 2 cm. Intrapartum and perinatal outcomes were compared between participants with a diagnosis of a low AFV by grayscale and color Doppler sonography., Results: Over 42 months, 428 women were enrolled in the study. Color Doppler sonography resulted in lower AFV estimates (mean ± SD by the AFI, 10.7 ± 3.7 cm by grayscale sonography and 8.6 ± 3.6cm by color Doppler sonography; P < .0001). For the SDP, the mean AFVs were 4.6 ± 2.0 cm by grayscale sonography and 3.4 ± 1.4 cm by color Doppler sonography (P < .0001). The level of agreement between grayscale and color Doppler sonography in estimating the AFV was fair, with κ = 0.32 for the AFI and 0.28 for the SDP. Outcome measures of AFVs classified as low based on color Doppler sonography (normal by grayscale sonography) and those classified as low by grayscale sonography (low by color Doppler sonography) were compared. There was no difference in composite perinatal complications, mode of delivery, or composite neonatal complications., Conclusions: The use of color Doppler sonography leads to the overdiagnosis of low AFVs and does not appear to increase the detection of pregnancies destined for adverse intrapartum or perinatal outcomes., (© 2017 by the American Institute of Ultrasound in Medicine.)

This study has demonstrated the use of crystallography, topology and graph set analysis in the description and classification of the complex hydrogen bonded network of triamterene. The aim is to give a brief overview of the methodology used to discuss the crystal structure of triamterene with a view to extending the study to include the solvates, cocrystals and salts of this compound. Graphical abstract One of the structurally significant dimers (supramolecular synthons) of triamterene identified by this study.

The evaluation of amniotic fluid volume (AFV) is an established part of the antenatal surveillance of pregnancies at risk for an adverse pregnancy outcome. The two most commonly used ultrasound techniques to estimate AFV are the amniotic fluid index (AFI) and the single deepest pocket (SDP). Four studies have defined normal AFVs, and although their normal volumes have similarities, there are also differences primarily due to the statistical methodology used in each study. Dye-determined AFV correlates with ultrasound estimates for normal fluid volumes but correlates poorly for oligohydramnios and polyhydramnios. The addition of color Doppler in estimating AFV leads to the overdiagnosis of oligohydramnios. Neither the AFI nor the SDP is superior in identifying oligohydramnios, but the SDP is a better measurement choice as the use of AFI increases the diagnosis rate of oligohydramnios and labor inductions without an improvement in pregnancy outcomes., (Copyright © 2016. Published by Elsevier Ltd.)

Background: Relatively little is known about the genomic basis and evolution of wood-feeding in beetles. We undertook genome sequencing and annotation, gene expression assays, studies of plant cell wall degrading enzymes, and other functional and comparative studies of the Asian longhorned beetle, Anoplophora glabripennis, a globally significant invasive species capable of inflicting severe feeding damage on many important tree species. Complementary studies of genes encoding enzymes involved in digestion of woody plant tissues or detoxification of plant allelochemicals were undertaken with the genomes of 14 additional insects, including the newly sequenced emerald ash borer and bull-headed dung beetle., Results: The Asian longhorned beetle genome encodes a uniquely diverse arsenal of enzymes that can degrade the main polysaccharide networks in plant cell walls, detoxify plant allelochemicals, and otherwise facilitate feeding on woody plants. It has the metabolic plasticity needed to feed on diverse plant species, contributing to its highly invasive nature. Large expansions of chemosensory genes involved in the reception of pheromones and plant kairomones are consistent with the complexity of chemical cues it uses to find host plants and mates., Conclusions: Amplification and functional divergence of genes associated with specialized feeding on plants, including genes originally obtained via horizontal gene transfer from fungi and bacteria, contributed to the addition, expansion, and enhancement of the metabolic repertoire of the Asian longhorned beetle, certain other phytophagous beetles, and to a lesser degree, other phytophagous insects. Our results thus begin to establish a genomic basis for the evolutionary success of beetles on plants.

Background: The Mediterranean fruit fly (medfly), Ceratitis capitata, is a major destructive insect pest due to its broad host range, which includes hundreds of fruits and vegetables. It exhibits a unique ability to invade and adapt to ecological niches throughout tropical and subtropical regions of the world, though medfly infestations have been prevented and controlled by the sterile insect technique (SIT) as part of integrated pest management programs (IPMs). The genetic analysis and manipulation of medfly has been subject to intensive study in an effort to improve SIT efficacy and other aspects of IPM control., Results: The 479 Mb medfly genome is sequenced from adult flies from lines inbred for 20 generations. A high-quality assembly is achieved having a contig N50 of 45.7 kb and scaffold N50 of 4.06 Mb. In-depth curation of more than 1800 messenger RNAs shows specific gene expansions that can be related to invasiveness and host adaptation, including gene families for chemoreception, toxin and insecticide metabolism, cuticle proteins, opsins, and aquaporins. We identify genes relevant to IPM control, including those required to improve SIT., Conclusions: The medfly genome sequence provides critical insights into the biology of one of the most serious and widespread agricultural pests. This knowledge should significantly advance the means of controlling the size and invasive potential of medfly populations. Its close relationship to Drosophila, and other insect species important to agriculture and human health, will further comparative functional and structural studies of insect genomes that should broaden our understanding of gene family evolution.

Subclonal mutations reveal important features of the genetic architecture of tumors. However, accurate detection of mutations in genetically heterogeneous tumor cell populations using next-generation sequencing remains challenging. We develop MuSE ( http://bioinformatics.mdanderson.org/main/MuSE ), Mutation calling using a Markov Substitution model for Evolution, a novel approach for modeling the evolution of the allelic composition of the tumor and normal tissue at each reference base. MuSE adopts a sample-specific error model that reflects the underlying tumor heterogeneity to greatly improve the overall accuracy. We demonstrate the accuracy of MuSE in calling subclonal mutations in the context of large-scale tumor sequencing projects using whole exome and whole genome sequencing.

Rhodnius prolixus not only has served as a model organism for the study of insect physiology, but also is a major vector of Chagas disease, an illness that affects approximately seven million people worldwide. We sequenced the genome of R. prolixus, generated assembled sequences covering 95% of the genome (∼ 702 Mb), including 15,456 putative protein-coding genes, and completed comprehensive genomic analyses of this obligate blood-feeding insect. Although immune-deficiency (IMD)-mediated immune responses were observed, R. prolixus putatively lacks key components of the IMD pathway, suggesting a reorganization of the canonical immune signaling network. Although both Toll and IMD effectors controlled intestinal microbiota, neither affected Trypanosoma cruzi, the causal agent of Chagas disease, implying the existence of evasion or tolerance mechanisms. R. prolixus has experienced an extensive loss of selenoprotein genes, with its repertoire reduced to only two proteins, one of which is a selenocysteine-based glutathione peroxidase, the first found in insects. The genome contained actively transcribed, horizontally transferred genes from Wolbachia sp., which showed evidence of codon use evolution toward the insect use pattern. Comparative protein analyses revealed many lineage-specific expansions and putative gene absences in R. prolixus, including tandem expansions of genes related to chemoreception, feeding, and digestion that possibly contributed to the evolution of a blood-feeding lifestyle. The genome assembly and these associated analyses provide critical information on the physiology and evolution of this important vector species and should be instrumental for the development of innovative disease control methods.

Objectives: To compare the fetal mortality rate in the Delta counties of a state in the Mississippi Delta region of the United States with that of the non-Delta counties of the same state., Methods: Hospital discharge data for maternal hospitalizations were linked to fetal death and birth certificates for 2004-2010. Data on maternal characteristics and comorbidities and pregnancy characteristics and outcomes were evaluated. The frequency of characteristics of pregnant women and pregnancy outcomes between Delta and non-Delta areas of the state was compared., Results: There were a total of 248,255 singleton births, of which 35,605 occurred in the Delta counties. Delta patients were more likely to be younger than 20 years old, African American, multigravida, Medicaid recipients, smokers, and not married (P < 0.001) when compared with the non-Delta patients. The overall odds of fetal death within Delta counties are 1.40 times (95% confidence interval [CI] 1.22-1.61) higher than the non-Delta counties, and the odds of fetal death at ≤28 weeks are 1.56 times (95% CI 1.28-1.91) higher. After controlling for maternal age, race/ethnicity, level of prenatal care, and maternal comorbidities, the odds of fetal death remained 1.21 times higher (95% CI 1.05-1.41) and 1.28 times higher at ≤28 weeks' gestational age (95% CI 1.03-1.60)., Conclusions: Fetal mortality is significantly greater in the Delta counties compared with the non-Delta counties, with a 21% increase in the odds of overall fetal death in the Delta counties compared with non-Delta counties and a 28% increase in the odds of fetal death at ≤28 weeks.

Lucilia cuprina is a parasitic fly of major economic importance worldwide. Larvae of this fly invade their animal host, feed on tissues and excretions and progressively cause severe skin disease (myiasis). Here we report the sequence and annotation of the 458-megabase draft genome of Lucilia cuprina. Analyses of this genome and the 14,544 predicted protein-encoding genes provide unique insights into the fly's molecular biology, interactions with the host animal and insecticide resistance. These insights have broad implications for designing new methods for the prevention and control of myiasis.

A program was developed for referred, stable, high-risk obstetrical patients allowing them to receive antenatal care close to a tertiary hospital without the costs of a hospital admission. There were 426 women managed from September 2007 through December of 2012 with diagnosis of preterm labor, fetal anomalies, hypertensive disorders, placental abruption and other conditions. This management saved the hospital almost $9,000,000 USD or $20,956 USD per patient., (Copyright © 2015 Elsevier B.V. All rights reserved.)

Background: Structural systematics is the comparison of sets of chemically related crystal structures with the aim to establish and describe relevant similarities and relationships. An important topic in this context is the comparison of hydrogen-bonded structures (HBSs) and their representation by suitable descriptors., Results: Three different description methods for HBSs are proposed, a graphical representation, a symbolic representation and connectivity tables. The most comprehensive description is provided by a modified graph of the underlying net topology of an HBS which contains information on the multiplicity of links, the directionality and chemical connectivity of hydrogen bonds and on symmetry relations. By contrast, the alternative symbolic representation is restricted to essential properties of an HBS, i.e. its dimensionality, topology type and selected connectivity characteristics of nodes. A comparison of their connectivity tables readily identifies differences and similarities between crystal structures with respect to the intermolecular interaction modes adopted by their functional groups. The application of these methods to the known polymorphs of sulfathiazole and sulfapyridine is demonstrated and it is shown that they enable the rationalisation of previously reported and intricate relationships., Conclusions: The proposed methods facilitate the comprehensive description of the most important relevant aspects of an HBS, including its chemical connectivity, net topology and symmetry characteristics, and they represent a new way to recognise similarities and relationships in organic crystal structures. Graphical AbstractGraphical Representation of mixing of structures StzIV and StzV to give structure StzIII.

Variation in vectorial capacity for human malaria among Anopheles mosquito species is determined by many factors, including behavior, immunity, and life history. To investigate the genomic basis of vectorial capacity and explore new avenues for vector control, we sequenced the genomes of 16 anopheline mosquito species from diverse locations spanning ~100 million years of evolution. Comparative analyses show faster rates of gene gain and loss, elevated gene shuffling on the X chromosome, and more intron losses, relative to Drosophila. Some determinants of vectorial capacity, such as chemosensory genes, do not show elevated turnover but instead diversify through protein-sequence changes. This dynamism of anopheline genes and genomes may contribute to their flexible capacity to take advantage of new ecological niches, including adapting to humans as primary hosts., (Copyright © 2015, American Association for the Advancement of Science.)

Background: Information about the diagnosis and management of late abdominal pregnancies (≥20 weeks gestation) is limited to case reports and small case series., Methods: We performed a literature review of abdominal pregnancies ≥20 weeks gestation from 1965 to November 2012. Excluded were abdominal ectopic pregnancies that did not primarily implant in the peritoneal cavity, including tubal, ovarian, and intraligamentary pregnancies, and those prior to 20 weeks gestation., Results: The 31 cases identified were at 30.4 ± 7.4 weeks at diagnosis and 33 ± 8.3 weeks at delivery. The most common sites of placental implantation were uterus or adnexa (47.8%), bowel (30%), and the potential spaces surrounding the uterus (8.7%). There were 5 cases of an intra-abdominal abscess in the 14 patients in whom the placenta had been left in situ. Maternal outcomes were documented in 26 cases with 7 deaths; 27 fetal outcomes were documented in 22 cases with 3 fetal deaths (13.6%)., Conclusion: An abdominal ectopic pregnancy is an uncommon but serious event and should be considered in all patients until intrauterine gestation is confirmed. Management should be undertaken by an experienced surgical team in a tertiary care facility., (© 2015 S. Karger AG, Basel.)

Background: Derivatives of fulgides have been shown to have interesting photochromic properties. We have synthesised a number of such derivatives and have found, in some cases, that crystals can be made to change colour on crushing, a phenomenon we have termed "tribochromism". We have studied a number of derivatives by X-ray crystallography, to see if the colour is linked to molecular structure or crystal packing, or both, and our structural results have been supported by calculation of molecular and lattice energies., Results: A number of 5-dicyanomethylene-4-diphenylmethylene-3-disubstitutedmethylene-tetrahydrofuran-2-one compounds have been prepared and structurally characterised. The compounds are obtained as yellow or dark red crystals, or, in one case, both. In two cases where yellow crystals were obtained, we found that crushing the crystals gave a deep red powder. Structure determinations, including those of the one compound which gave both coloured forms, depending on crystallisation conditions, showed that the yellow crystals contained molecules in which the structure comprised a folded conformation at the diphenylmethylene site, whilst the red crystals contained molecules in a twisted conformation at this site. Lattice energy and molecular conformation energies were calculated for all molecules, and showed that the conformational energy of the molecule in structure IIIa (yellow) is marginally higher, and the conformation thus less stable, than that of the molecule in structure IIIb (red). However, the van der Waals energy for crystal structure IIIa, is slightly stronger than that of structure IIIb - which may be viewed as a hint of a metastable packing preference for IIIa, overcome by the contribution of a more stabilising Coulomb energy to the overall more favourable lattice energy of structure IIIb., Conclusions: Our studies have shown that the crystal colour is correlated with one of two molecular conformations which are different in energy, but that the less stable conformation can be stabilised by its host crystal lattice. Graphical abstractGraphical representation of the structural and colour change in the tribochromic compound (III).

Myriapods (e.g., centipedes and millipedes) display a simple homonomous body plan relative to other arthropods. All members of the class are terrestrial, but they attained terrestriality independently of insects. Myriapoda is the only arthropod class not represented by a sequenced genome. We present an analysis of the genome of the centipede Strigamia maritima. It retains a compact genome that has undergone less gene loss and shuffling than previously sequenced arthropods, and many orthologues of genes conserved from the bilaterian ancestor that have been lost in insects. Our analysis locates many genes in conserved macro-synteny contexts, and many small-scale examples of gene clustering. We describe several examples where S. maritima shows different solutions from insects to similar problems. The insect olfactory receptor gene family is absent from S. maritima, and olfaction in air is likely effected by expansion of other receptor gene families. For some genes S. maritima has evolved paralogues to generate coding sequence diversity, where insects use alternate splicing. This is most striking for the Dscam gene, which in Drosophila generates more than 100,000 alternate splice forms, but in S. maritima is encoded by over 100 paralogues. We see an intriguing linkage between the absence of any known photosensory proteins in a blind organism and the additional absence of canonical circadian clock genes. The phylogenetic position of myriapods allows us to identify where in arthropod phylogeny several particular molecular mechanisms and traits emerged. For example, we conclude that juvenile hormone signalling evolved with the emergence of the exoskeleton in the arthropods and that RR-1 containing cuticle proteins evolved in the lineage leading to Mandibulata. We also identify when various gene expansions and losses occurred. The genome of S. maritima offers us a unique glimpse into the ancestral arthropod genome, while also displaying many adaptations to its specific life history., Competing Interests: The authors have declared that no competing interests exist.

We present a rare case of unilateral lateral rectus palsy following an elective coronary angiography and percutaneous coronary intervention in a 78-year-old woman. Ophthalmoplegia following coronary angiography is extremely rare and this is the first case of a unilateral lateral rectus palsy following the procedure.

Ensembl Genomes (http://www.ensemblgenomes.org) is an integrating resource for genome-scale data from non-vertebrate species. The project exploits and extends technologies for genome annotation, analysis and dissemination, developed in the context of the vertebrate-focused Ensembl project, and provides a complementary set of resources for non-vertebrate species through a consistent set of programmatic and interactive interfaces. These provide access to data including reference sequence, gene models, transcriptional data, polymorphisms and comparative analysis. This article provides an update to the previous publications about the resource, with a focus on recent developments. These include the addition of important new genomes (and related data sets) including crop plants, vectors of human disease and eukaryotic pathogens. In addition, the resource has scaled up its representation of bacterial genomes, and now includes the genomes of over 9000 bacteria. Specific extensions to the web and programmatic interfaces have been developed to support users in navigating these large data sets. Looking forward, analytic tools to allow targeted selection of data for visualization and download are likely to become increasingly important in future as the number of available genomes increases within all domains of life, and some of the challenges faced in representing bacterial data are likely to become commonplace for eukaryotes in future.

Ensembl Genomes (http://www.ensemblgenomes.org) is an integrative resource for genome-scale data from non-vertebrate species. The project exploits and extends technology (for genome annotation, analysis and dissemination) developed in the context of the (vertebrate-focused) Ensembl project and provides a complementary set of resources for non-vertebrate species through a consistent set of programmatic and interactive interfaces. These provide access to data including reference sequence, gene models, transcriptional data, polymorphisms and comparative analysis. Since its launch in 2009, Ensembl Genomes has undergone rapid expansion, with the goal of providing coverage of all major experimental organisms, and additionally including taxonomic reference points to provide the evolutionary context in which genes can be understood. Against the backdrop of a continuing increase in genome sequencing activities in all parts of the tree of life, we seek to work, wherever possible, with the communities actively generating and using data, and are participants in a growing range of collaborations involved in the annotation and analysis of genomes.

VectorBase (http://www.vectorbase.org) is a NIAID-supported bioinformatics resource for invertebrate vectors of human pathogens. It hosts data for nine genomes: mosquitoes (three Anopheles gambiae genomes, Aedes aegypti and Culex quinquefasciatus), tick (Ixodes scapularis), body louse (Pediculus humanus), kissing bug (Rhodnius prolixus) and tsetse fly (Glossina morsitans). Hosted data range from genomic features and expression data to population genetics and ontologies. We describe improvements and integration of new data that expand our taxonomic coverage. Releases are bi-monthly and include the delivery of preliminary data for emerging genomes. Frequent updates of the genome browser provide VectorBase users with increasing options for visualizing their own high-throughput data. One major development is a new population biology resource for storing genomic variations, insecticide resistance data and their associated metadata. It takes advantage of improved ontologies and controlled vocabularies. Combined, these new features ensure timely release of multiple types of data in the public domain while helping overcome the bottlenecks of bioinformatics and annotation by engaging with our user community.

Background: The polarization of somite-derived sclerotomes into anterior and posterior halves underlies vertebral morphogenesis and spinal nerve segmentation. To characterize the full extent of molecular differences that underlie this polarity, we have undertaken a systematic comparison of gene expression between the two sclerotome halves in the mouse embryo., Results: Several hundred genes are differentially-expressed between the two sclerotome halves, showing that a marked degree of molecular heterogeneity underpins the development of somite polarity., Conclusion: We have identified a set of genes that warrant further investigation as regulators of somite polarity and vertebral morphogenesis, as well as repellents of spinal axon growth. Moreover the results indicate that, unlike the posterior half-sclerotome, the central region of the anterior-half-sclerotome does not contribute bone and cartilage to the vertebral column, being associated instead with the development of the segmented spinal nerves.

The role of human papillomavirus (HPV) infection in eye disease is controversial. However, a recent case illustrates the possible role of HPV in conjunctival squamous carcinoma and the potentially devastating effects of this disease. The development of two vaccines to prevent infection with HPV types most commonly associated with anogenital cancers has led to debate about the pros and cons of a national immunisation programme to prevent cervical cancer. The introduction of such a vaccination programme may have an additional beneficial effect on the occurrence of some head and neck, including ocular, cancers. This review discusses the nature of papillomaviruses, mechanisms of infection and carcinogenesis, the possible role of HPV in eye disease, and finally the likely impact of the new prophylactic vaccines.

Reassessment of the reported single-crystal X-ray diffraction characterization of polymorphs of furosemide and finasteride shows that, in each case, incomplete data collections have resulted in the mistaken identification of two forms that are, in fact, identical.

Purpose: To evaluate the role of topical non-steroidal anti-inflammatory agents (NSAIDs) in the management of corneal abrasions with respect to symptoms and healing., Methods: The study was designed as a prospective, single center, randomised, placebo controlled, double-blinded trial. Eighty-eight consecutive patients with non-infective, non-contact lens related traumatic or foreign body removal related corneal abrasions were recruited to this study. They were randomised into two groups. Both groups were given a single instillation of Gutt. cyclopentolate 0.5% followed by chloramphenicol eye ointment four times a day until the following day. In addition, the treatment group received topical Ketorolac trometamol 0.5% ophthalmic solution while the control group received placebo Liquifilm tears. Patients were assessed at presentation and about twenty-four hours later for subjective symptoms, abrasion size and any associated complications., Results: There was no statistical difference in the two groups at base line and twenty-four hour follow-up when assessed for five subjective symptoms of pain, photophobia, grittiness, watering and blurring of vision. However, those receiving topical ketorolac required significantly less additional oral analgesics (p=0.001). There was no difference in the rate of healing., Conclusion: Use of topical ketorolac may be a useful adjunct in the management of corneal abrasions.

A series of pyrroles substituted with various electron-withdrawing groups (EWGs) on the N atom have been synthesized and full characterization including X-ray crystal structures obtained. Analysis of (13)C chemical shifts and X-ray crystal structures reveals that a trend between decreased aromaticity and the strength of the EWG exists. Experimental results regarding alternative mechanisms of nucleophilic substitution reactions can thus be rationalized.

Purpose: To establish the rate of complications detected on the first postoperative day and therefore the need for evaluation on that day., Setting: Hinchingbrooke Hospital, Huntingdon, England., Methods: Complications detected on the first day after phacoemulsification cataract surgery were retrospectively reviewed over 8 months. Ophthalmic nurse practitioners performed the 1 day postoperative examination and kept a log of patients seen, recording complications detected and whether referral to a physician was required. All patients had had routine phacoemulsification with intraocular lens implantation without anterior vitrectomy or trabeculectomy, as identified from the log book and cross-checked with operating theater records. Notes were reviewed if a complication or referral was recorded. Most cases were performed under local anesthesia as day cases using a temporal corneal approach. Sections were routinely left unsutured unless enlarged or closure was not satisfactory at the conclusion of surgery., Results: The review yielded 392 patients. Six (1.53%) had intraocular pressure (> or = 30 mm Hg) requiring treatment, 1 (0.26%) had painless iris prolapse, 11 (2.81%) had corneal abrasions, and 7 (1.78%) were given a more intensive steroid regime. No cases of fibrinous uveitis were recorded., Conclusions: Potentially sight-threatening complications present on the first postoperative day, albeit infrequently. With our current practice and case mix, the need for this review persists. It is possible to reduce the demand on physician time by using appropriately trained nonmedical practitioners.

The uncultivated bacterial endosymbionts of the hydrothermal vent tubeworm Riftia pachyptila play a central role in providing their host with fixed carbon. While this intimate association between host and symbiont indicates tight integration and coordination of function via cellular communication mechanisms, no such systems have been identified. To elucidate potential signal transduction pathways in symbionts that may mediate symbiont-host communication, we cloned and characterized a gene encoding a histidine protein kinase homolog isolated from a symbiont fosmid library. The gene, designated rssA (for Riftia symbiont signal kinase), resembles known sensor kinases and encodes a protein capable of phosphorylating response regulators in Escherichia coli. A second open reading frame, rssB (for Riftia symbiont signal regulator), encodes a protein similar to known response regulators. These results suggest that the symbionts utilize a phosphotransfer signal transduction mechanism to communicate external signals that may mediate recognition of or survival within the host. The specific signals eliciting a response by the signal transduction proteins of the symbiont remain to be elucidated.

A laboratory culture of Mamestra brassicae insects (MbLC) harbours a latent or occult baculovirus that resembles M. brassicae multiple nucleocapsid nucleopolyhedrovirus (MbMNPV). Although conventional extraction techniques have failed to detect the presence of virus in MbLC, control virus-free insects (MbWS) died of an MbMNPV-like infection after being fed MbLC fat-body cells. This suggested that the MbLC cells harboured infectious MbMNPV, albeit at low levels. We have also demonstrated that fat-body cells from MbLC, but not from MbWS, contain mRNA specific for the polyhedrin gene and transcriptional factors that are capable of activating baculovirus late and very late gene promoters linked to a reporter gene encoding chloramphenicol acetyltransferase. Our data provide indirect evidence that the latent MbMNPV in the MbLC insects is maintained as a persistent infection, with the expression of viral genes at a low level.

Replication deficient, recombinant adenoviruses (Ads) have been used successfully to transfect several forebrain and brainstem nuclei, but have yet to be demonstrated as useful vectors for transgene delivery in the structurally diverse and highly vascularised nuclei of the hypothalamus. In the present study we have assessed the ability of an Ad expressing the lac-Z gene to transfect cells of the paraventricular nucleus (PVN) of the hypothalamus in vivo. We show that: (1) we can achieve stable expression of the lacZ gene in cells of the magnocellular PVN for at least 2 months; (2) there were no obvious differences in the level of AVP mRNA in the PVNs injected with Ad compared with those injected with vehicle suggesting that Ad treatment is not disrupting normal cellular function in the injection region; (3) the introduction of Ads results in a limited immune response; (4) systemic treatment with cyclosporin dramatically reduces its magnitude. We conclude that Ad vectors represent useful tools for neuroendocrinological and gene therapeutic studies of the hypothalamus.

Purpose: We used superior oblique luxation and trochlear luxation as new surgical procedures to treat acquired Brown's syndrome and superior oblique muscle overaction., Methods: We studied nine patients (11 eyes) who underwent trochlear surgery between 1988 and 1993. Four patients had acquired Brown's syndrome and five had superior oblique muscle overaction. In five patients (six eyes) the trochlea was incised to luxate the superior oblique tendon out of the trochlea. In four patients (five eyes) the trochlea was luxated out of its fossa via a periosteal approach without opening the trochlea itself., Results: The mean follow-up was 18 months (range, nine to 33 months). Postoperatively, eight patients showed subjective and objective improvement. One patient with painful traumatic acquired Brown's syndrome had no objective improvement but obtained relief of pain., Conclusions: These new techniques are a successful alternative in the treatment of acquired Brown's syndrome and superior oblique muscle overaction.

A laboratory culture of Mamestra brassicae insects (MbLC) was found to harbour a latent baculovirus infection. The copy number of the occult MbNPV genome in both the MbLC larvae, and in a cell line derived from the fat body of MbLC was determined by the use of a rapid and convenient PCR-scintillation proximity assay (SPA). The SPA system relies on the use of fluomicrospheres (SPA beads) coated with acceptor molecules which are capable of binding radiolabelled ligands in solution. In the assay described, a biotinylated PCR primer is used and [3H]dNTPs are incorporated into the amplified DNA. The SPA beads are coated with streptavidin, and after binding the biotinylated primer, any amplified, radiolabelled DNA will activate the fluor. The amount of amplified DNA from the target sequence can then be directly quantified using a scintillation counter. The number of MbNPV genomes present in a persistently infected M. brassicae cell, as proposed by SPA, suggest between 13 and 20 copies of the viral genome may be present in individual fat body cells.