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Background: Efgartigimod, a human immunoglobulin (Ig)G1 antibody Fc fragment, blocks the neonatal Fc receptor, reducing IgGs involved in chronic inflammatory demyelinating polyneuropathy (CIDP). The multi-stage, double-blinded, placebo-controlled ADHERE (NCT04281472) and open-label extension ADHERE+ (NCT04280718) trials (interim analysis cutoff: February 16, 2024) assessed efgartigimod PH20 SC in participants with CIDP. Methods: Participants with active CIDP received open-label, weekly efgartigimod PH20 SC 1000 mg during ≤12-week run-in (stage-A). Responders were randomized (1:1) to efgartigimod or placebo for ≤48 weeks (stage-B). Participants with clinical deterioration in stage-B or who completed ADHERE entered ADHERE+. Week 36 changes from run-in baseline (CFB) in adjusted Inflammatory Neuropathy Cause and Treatment (aINCAT), Inflammatory Rasch-built Overall Disability Scale (I-RODS), and grip strength scores were evaluated. Results: Of 322 stage-A participants, 221 were randomized and treated in stage-B, and 99% entered ADHERE+. Mean CFB (SE) in aINCAT, I-RODS, and grip strength scores were -1.2 (0.15) and 8.8 (1.46) and 17.5 (2.02), respectively, at ADHERE+ Week 36 (N=150). Half the participants with clinical deterioration during ADHERE stage-B restabilized on efgartigimod from ADHERE+ Week 4. Conclusions: Interim results from ADHERE+ indicate long-term effectiveness of efgartigimod PH20 SC in clinical outcomes in participants with CIDP.
Background: Efgartigimod, a human immunoglobulin (Ig)G1 antibody Fc fragment, blocks the neonatal Fc receptor, reducing IgGs involved in chronic inflammatory demyelinating polyneuropathy (CIDP), a rare, progressive, immune-mediated disease that can lead to irreversible disability. The multi-stage, double-blinded, placebo-controlled ADHERE (NCT04281472) trial assessed efgartigimod PH20 SC in participants with CIDP. Methods: Participants with active CIDP received open-label, weekly efgartigimod PH20 SC 1000 mg during ≤12-week run-in (stage-A). Responders were randomized (1:1) to weekly efgartigimod or placebo for ≤48 weeks (stage-B). This posthoc analysis evaluated changes from run-in baseline (study enrollment) to stage-B last assessment and items of the Inflammatory Rasch-built Overall Disability Scale (I-RODS). Results: Of 322 participants who entered stage-A, 221 were randomized and treated in stage-B, and 191/221 had data for run-in baseline and post–stage-B timepoints. Mean (SE) I-RODS change at stage-B last assessment vs run-in baseline was 5.7 (1.88) and -4.9 (1.82) in participants randomized to efgartigimod and placebo, respectively. 37/97 (38.1%) and 24/92 (26.1%) participants randomized to efgartigimod and placebo, respectively, experienced ≥4-point improvements in I-RODS score. Efgartigimod-treated participants improved ≥1 point in I-RODS items of clinical interest. Conclusions: Participants who received efgartigimod in stage-B experienced improvements in I-RODS score from study enrollment to stage-B last assessment.
In response to the COVID-19 pandemic, we rapidly implemented a plasma coordination center, within two months, to support transfusion for two outpatient randomized controlled trials. The center design was based on an investigational drug services model and a Food and Drug Administration-compliant database to manage blood product inventory and trial safety.
Methods:
A core investigational team adapted a cloud-based platform to randomize patient assignments and track inventory distribution of control plasma and high-titer COVID-19 convalescent plasma of different blood groups from 29 donor collection centers directly to blood banks serving 26 transfusion sites.
Results:
We performed 1,351 transfusions in 16 months. The transparency of the digital inventory at each site was critical to facilitate qualification, randomization, and overnight shipments of blood group-compatible plasma for transfusions into trial participants. While inventory challenges were heightened with COVID-19 convalescent plasma, the cloud-based system, and the flexible approach of the plasma coordination center staff across the blood bank network enabled decentralized procurement and distribution of investigational products to maintain inventory thresholds and overcome local supply chain restraints at the sites.
Conclusion:
The rapid creation of a plasma coordination center for outpatient transfusions is infrequent in the academic setting. Distributing more than 3,100 plasma units to blood banks charged with managing investigational inventory across the U.S. in a decentralized manner posed operational and regulatory challenges while providing opportunities for the plasma coordination center to contribute to research of global importance. This program can serve as a template in subsequent public health emergencies.
The U.S. Department of Agriculture–Agricultural Research Service (USDA-ARS) has been a leader in weed science research covering topics ranging from the development and use of integrated weed management (IWM) tactics to basic mechanistic studies, including biotic resistance of desirable plant communities and herbicide resistance. ARS weed scientists have worked in agricultural and natural ecosystems, including agronomic and horticultural crops, pastures, forests, wild lands, aquatic habitats, wetlands, and riparian areas. Through strong partnerships with academia, state agencies, private industry, and numerous federal programs, ARS weed scientists have made contributions to discoveries in the newest fields of robotics and genetics, as well as the traditional and fundamental subjects of weed–crop competition and physiology and integration of weed control tactics and practices. Weed science at ARS is often overshadowed by other research topics; thus, few are aware of the long history of ARS weed science and its important contributions. This review is the result of a symposium held at the Weed Science Society of America’s 62nd Annual Meeting in 2022 that included 10 separate presentations in a virtual Weed Science Webinar Series. The overarching themes of management tactics (IWM, biological control, and automation), basic mechanisms (competition, invasive plant genetics, and herbicide resistance), and ecosystem impacts (invasive plant spread, climate change, conservation, and restoration) represent core ARS weed science research that is dynamic and efficacious and has been a significant component of the agency’s national and international efforts. This review highlights current studies and future directions that exemplify the science and collaborative relationships both within and outside ARS. Given the constraints of weeds and invasive plants on all aspects of food, feed, and fiber systems, there is an acknowledged need to face new challenges, including agriculture and natural resources sustainability, economic resilience and reliability, and societal health and well-being.
The United Nations' sustainable development goals (SDGs) articulate societal aspirations for people and our planet. Many scientists have criticised the SDGs and some have suggested that a better understanding of the complex interactions between society and the environment should underpin the next global development agenda. We further this discussion through the theory of social–ecological resilience, which emphasises the ability of systems to absorb, adapt, and transform in the face of change. We determine the strengths of the current SDGs, which should form a basis for the next agenda, and identify key gaps that should be filled.
Technical summary
The United Nations' sustainable development goals (SDGs) are past their halfway point and the next global development agenda will soon need to be developed. While laudable, the SDGs have received strong criticism from many, and scholars have proposed that adopting complex adaptive or social–ecological system approaches would increase the effectiveness of the agenda. Here we dive deeper into these discussions to explore how the theory of social–ecological resilience could serve as a strong foundation for the next global sustainable development agenda. We identify the strengths and weaknesses of the current SDGs by determining which of the 169 targets address each of 43 factors affecting social–ecological resilience that we have compiled from the literature. The SDGs with the strongest connections to social–ecological resilience are the environment-focus goals (SDGs 2, 6, 13, 14, 15), which are also the goals consistently under-prioritised in the implementation of the current agenda. In terms of the 43 factors affecting social–ecological resilience, the SDG strengths lie in their communication, inclusive decision making, financial support, regulatory incentives, economic diversity, and transparency in governance and law. On the contrary, ecological factors of resilience are seriously lacking in the SDGs, particularly with regards to scale, cross-scale interactions, and non-stationarity.
Social media summary
The post-2030 agenda should build on strengths of SDGs 2, 6, 13, 14, 15, and fill gaps in scale, variability, and feedbacks.
To describe the genomic analysis and epidemiologic response related to a slow and prolonged methicillin-resistant Staphylococcus aureus (MRSA) outbreak.
Design:
Prospective observational study.
Setting:
Neonatal intensive care unit (NICU).
Methods:
We conducted an epidemiologic investigation of a NICU MRSA outbreak involving serial baby and staff screening to identify opportunities for decolonization. Whole-genome sequencing was performed on MRSA isolates.
Results:
A NICU with excellent hand hygiene compliance and longstanding minimal healthcare-associated infections experienced an MRSA outbreak involving 15 babies and 6 healthcare personnel (HCP). In total, 12 cases occurred slowly over a 1-year period (mean, 30.7 days apart) followed by 3 additional cases 7 months later. Multiple progressive infection prevention interventions were implemented, including contact precautions and cohorting of MRSA-positive babies, hand hygiene observers, enhanced environmental cleaning, screening of babies and staff, and decolonization of carriers. Only decolonization of HCP found to be persistent carriers of MRSA was successful in stopping transmission and ending the outbreak. Genomic analyses identified bidirectional transmission between babies and HCP during the outbreak.
Conclusions:
In comparison to fast outbreaks, outbreaks that are “slow and sustained” may be more common to units with strong existing infection prevention practices such that a series of breaches have to align to result in a case. We identified a slow outbreak that persisted among staff and babies and was only stopped by identifying and decolonizing persistent MRSA carriage among staff. A repeated decolonization regimen was successful in allowing previously persistent carriers to safely continue work duties.
The application of paraquat mixtures with residual herbicides before planting rice is a common treatment in Mississippi, and rice in proximity is susceptible to off-target movement of these applications. Four concurrent studies were conducted in Stoneville, MS, to characterize rice performance following exposure to a sublethal rate of paraquat, metribuzin, fomesafen, and cloransulam-methyl at different application timings. Herbicides were applied to rice at the growth stages of spiking to one-leaf (VEPOST), two- to three-leaf (EPOST), three- to four-leaf (MPOST), 7 d postflood (PFLD), and panicle differentiation (PD). Regardless of application timing, rice injury following exposure to paraquat was ≥45%. Delays in maturity were increased by 0.3 d d−1 following paraquat from emergence through PD. Dry weight, rough rice yield, panicle density, and germination were reduced by 18.7 g, 131.5 kg ha−1, 5.6 m−2, and 0.3%, respectively, per day from application of paraquat at emergence through PD. By 28 d after treatment (DAT), metribuzin injured rice 3% to 6%, and that injury did not translate into a yield reduction. Regardless of application timing, rice injury following fomesafen application ranged from 2% to 5% 28 DAT. Rice exposed to cloransulam-methyl EPOST exhibited the greatest root and foliar injury 21 DAT and 28 DAT, respectively. Additionally, when rice was exposed to cloransulam-methyl EPOST, yield was reduced to 6,540 kg ha−1 compared with a yield of 7,850 kg ha−1 from nontreated rice. Rice yield was negatively affected after paraquat was applied any time after rice emergence. However, applications of paraquat to rice at early reproductive growth stages reduced rough rice yield and seed germination the greatest. Application timing is crucial in determining severity of rice injury. Early-season injury to rice following paraquat application had less effect on yield compared with injury at later stages. Additionally, fields devoted to seed rice production are at risk for reduced seed germination if they are exposed to paraquat during early reproductive growth stages.
Information on performance of sequential treatments of quizalofop-P-ethyl with florpyrauxifen-benzyl on rice is lacking. Field studies were conducted in 2017 and 2018 in Stoneville, MS, to evaluate sequential timings of quizalofop-P-ethyl with florpyrauxifen-benzyl included in preflood treatments of rice. Quizalofop-P-ethyl treatments were no quizalofop-P-ethyl; sequential applications of quizalofop-P-ethyl at 120 g ha−1 followed by (fb) 120 g ai ha−1 applied to rice in the 2- to 3-leaf (EPOST) fb the 4-leaf to 1-tiller (LPOST) growth stages or LPOST fb 10 d after flooding (PTFLD); quizalofop-P-ethyl at 100 g ha−1 fb 139 g ha−1 EPOST fb LPOST or LPOST fb PTFLD; quizalofop-P-ethyl at 139 g ha−1 fb 100 g ha−1 EPOST fb LPOST and LPOST fb PTFLD; and quizalofop-P-ethyl at 85 g ha−1 fb 77 g ha−1 fb 77 g ha−1 EPOST fb LPOST fb PTFLD. Quizalofop-P-ethyl was applied alone and in mixture with florpyrauxifen-benzyl at 29 g ai ha−1 LPOST. Visible rice injury 14 d after PTFLD (DA-PTFLD) was no more than 3%. Visible control of volunteer rice (‘CL151’ and ‘Rex’) 7 DA-PTFLD was similar and at least 95% for each quizalofop-P-ethyl treatment. Barnyardgrass control with quizalofop-P-ethyl at 120 fb 120 g ha−1 LPOST fb PTFLD was greater (88%) in mixture with florpyrauxifen-benzyl. The addition of florpyrauxifen-benzyl to quizalofop-P-ethyl increased rough rice yield when quizalofop-P-ethyl was applied at 100 g ha−1 fb 139 g ha−1 EPOST fb LPOST. Sequential applications of quizalofop-P-ethyl at 120 g ha−1 fb 120 g ha−1 EPOST fb LPOST, 100 g ha−1 fb 139 g ha−1 EPOST fb LPOST, or 139 g ha−1 fb 100 g ha−1 EPOST fb LPOST controlled grass weed species. The addition of florpyrauxifen-benzyl was not beneficial for grass weed control. However, because quizalofop-P-ethyl does not control broadleaf weeds, florpyrauxifen-benzyl could provide broad-spectrum weed control in acetyl coenzyme A carboxylase–resistant rice.
Florpyrauxifen-benzyl and quizalofop were available for POST applications in 2018; however, little is known about the response of acetyl-CoA carboxylase (ACCase)–resistant rice cultivars and advanced lines to POST herbicides. A field study was conducted in 2017 and 2018 at Stoneville, MS, to characterize the response of ACCase-resistant rice cultivars and advanced lines to POST applications of florpyrauxifen-benzyl. The imidazolinone-resistant (IR) rice cultivars ‘CL163’ and ‘CLXL 745’, and ACCase-resistant rice cultivars ‘PVL01’, ‘PVL013’, ‘PVL024-B’, ‘PVL038’, ‘PVL080’, and ‘PVL081’were treated with florpyrauxifen-benzyl at 0 (nontreated control for each cultivar) and 58 g ai ha–1 at the four-leaf to one-tiller (LPOST) growth stage. At 14 d after treatment (DAT), PVL01 was injured 5% to 6% greater than CLXL 745, PVL013, and PVL081; however, injury was ≤10% at that evaluation for all cultivars. Similarly, injury was ≤13% for all cultivars 28 DAT. Mature heights were reduced for all cultivars except PVL013 and PVL081. Rough rice yield was ≥100% of the control for all cultivars except PVL081, PVL013, and CL163. Results suggest that florpyrauxifen-benzyl can safely be applied POST to rice cultivars grown in Mississippi as well as ACCase-resistant cultivars that are currently under development.
Off-target paraquat movement to rice has become a major problem in recent years for rice producers in the midsouthern United States. Nitrogen (N) fertilizer is applied to rice in greater quantity and frequency than all other nutrients to optimize rice yield. Two separate field studies were conducted from 2015 to 2018 in Stoneville, MS, to assess whether starter N fertilizer can aid rice recovery from exposure to a sub-lethal concentration of paraquat and to evaluate rice response to different N fertilizer management strategies following exposure to a sub-lethal concentration of paraquat. In both studies, paraquat treatments consisted of paraquat at 0 and 84 g ai ha–1 applied to rice in the two- to three-leaf (EPOST) growth stage. In the starter fertilizer study, N fertilizer at 24 kg ha–1 as ammonium sulfate (AMS) was applied to rice at spiking- to one-leaf (VEPOST), two- to three-leaf (EPOST), or three- to four-leaf (MPOST) growth stages before and after paraquat treatment. In the N fertilizer timing study, N fertilizer at 168 kg N ha–1 was applied in a single four-leaf to one-tiller (LPOST) application or two-, three-, and two four-way split applications. Despite starter N fertilizer applications, paraquat injured rice ≥41%, reduced height 57%, reduced dry weight prior to flooding 77%, delayed maturity 10 d, reduced dry weight at maturity 33%, and reduced rough rice yield 35% in the starter fertilizer study. Similarly, in the N fertilizer timing study, paraquat injured rice ≥45%, reduced height 14%, delayed maturity 10 d, reduced dry weight at maturity 44%, and reduced rough rice yield 50% for all N fertilizer management strategies. Both studies indicate that severe complications in growth and development can occur from rice exposure to a sub-lethal concentration of paraquat. In both studies, manipulation of N fertilizer management did not facilitate rice recovery from early-season exposure to paraquat.
In glyphosate-resistant (GR) cropping systems, paraquat applied in mixtures with residual herbicides prior to crop emergence offers an alternative herbicide mode of action (MOA) to aid in GR weed management. Rice is sensitive to off-target herbicide movement; however, severity of injury can vary with herbicide, rate, and formulation. Therefore, research was conducted from 2015 to 2017 in Stoneville, MS, to characterize rice response to a sublethal concentration of paraquat applied at 84 g ai ha–1 in combination with common residual herbicides. Paraquat plus metribuzin injured rice 68% to 69% 14 and 28 d after treatment (DAT), which was 10% to 13% greater than injury following paraquat alone or paraquat plus fomesafen. Pooled across metribuzin and fomesafen treatments, paraquat reduced rough rice yields 23%. Paraquat plus 10 different residual herbicides injured rice ≥51% 28 DAT and reduced rough rice yields ≥21%. These studies indicate a severe negative impact on rice growth and development following exposure to a sublethal concentration of paraquat alone or in mixture with common residual herbicides. Therefore, applications of paraquat plus residual herbicides to fields in proximity to rice should be avoided if conditions are conducive for off-target movement.
Rice with enhanced tolerance to herbicides that inhibit acetyl coA carboxylase (ACCase) allows POST application of quizalofop, an ACCase-inhibiting herbicide. Two concurrent field studies were conducted in 2017 and 2018 near Stoneville, MS, to evaluate control of grass (Grass Study) and broadleaf (Broadleaf Study) weeds with sequential applications of quizalofop alone and in mixtures with auxinic herbicides applied in the first or second application. Sequential treatments of quizalofop were applied at 119 g ai ha−1 alone and in mixtures with labeled rates of auxinic herbicides to rice at the two- to three-leaf (EPOST) or four-leaf to one-tiller (LPOST) growth stages. In the Grass Study, no differences in rice injury or control of volunteer rice (‘CL151’ and ‘Rex’) were detected 14 and 28 d after last application (DA-LPOST). Barnyardgrass control at 14 and 28 DA-LPOST with quizalofop applied alone or with auxinic herbicides EPOST was ≥93% for all auxinic herbicide treatments except penoxsulam plus triclopyr. Barnyardgrass control was ≥96% with quizalofop applied alone and with auxinic herbicides LPOST. In the Broadleaf Study, quizalofop plus florpyrauxifen-benzyl controlled more Palmer amaranth 14 DA-LPOST than other mixtures with auxinic herbicides, and control with this treatment was greater EPOST compared with LPOST. Hemp sesbania control 14 DA-LPOST was ≤90% with quizalofop plus quinclorac LPOST, orthosulfamuron plus quinclorac LPOST, and triclopyr EPOST or LPOST. All mixtures except quinclorac and orthosulfamuron plus quinclorac LPOST controlled ivyleaf morningglory ≥91% 14 DA-LPOST. Florpyrauxifen-benzyl or triclopyr were required for volunteer soybean control >63% 14 DA-LPOST. To optimize barnyardgrass control and rice yield, penoxsulam plus triclopyr and orthosulfamuron plus quinclorac should not be mixed with quizalofop. Quizalofop mixtures with auxinic herbicides are safe and effective for controlling barnyardgrass, volunteer rice, and broadleaf weeds in ACCase-resistant rice, and the choice of herbicide mixture could be adjusted based on weed spectrum in the treated field.
Additional crystallographic data are given for the recently reported mineral middlebackite, which has been described for discoveries at Iron Knob in South Australia and Passo di San Lugano near Trento, Italy. The material examined in the present study was from a third finding of the mineral, viz. from a quartz outcrop at Mooloo Downs Station in Western Australia within which it was co-located with the chemically- and structurally-related mineral moolooite, CuIIC2O4·nH2O, reported by Clarke and Williams (1986). In this study, the crystal structure was elucidated independently of the other studies using a combination of the a priori charge flipping and simulated annealing methods with synchrotron radiation diffraction (SRD) powder data. The principal crystal data for the Mooloo Downs material are: space group P21/c with lattice parameters a = 7.2659(18) Å, b = 5.7460(11) Å, c = 5.6806(11) Å, β = 104.588(3)°; Vc = 229.46(18) Å3; empirical formula CuII2C2O4(OH)2 with 2 formula units per unit cell; and calculated density = 3.605 g cm−3. The lattice parameters agree approximately with values given for the other studies, but not within the reported error estimates. The atom coordinates, interatomic distances, and angles for the Mooloo Downs material are compared with those from the other studies using single crystal data, with the values from all three studies agreeing approximately, but again not within the reported uncertainties. The crystal chemistry found for middlebackite received strong confirmation through the synthesis for the first time of di-copper oxalate di-hydroxide. Laboratory X-ray diffraction powder data for the synthetic form of the mineral from this study agree closely with the SRD data for the natural mineral.
In 2017, we surveyed long-term care facilities in Pennsylvania regarding antimicrobial stewardship and infection prevention and control (IPC) practices. Among 244 responding facilities, 93% had IPC programs and 47% had antimicrobial stewardship programs. There was significant variation in practices across facilities, and a number of program implementation challenges were identified.
Background: Most people with common mental health problems do not seek evidence-based psychological interventions. Aims: The aim of this study was to investigate whether monitoring symptoms of depression and anxiety using an app increased treatment-seeking. Method: Three hundred and six people with significant levels of anxiety and depression, none of whom were currently receiving treatment, were randomly allocated to receive either (a) information about local psychological services only, (b) information plus regular symptom monitoring (every 6 days), or (c) information plus open symptom monitoring (monitoring when they felt like it). An app was used to provide information and monitor mood. Results: The proportion of participants who reported receiving treatment after starting the study was 7.2% (10/138) in the information only group, 8.1% (9/111) in the information plus regular monitoring group and 15.8% (9/57) in the information plus open monitoring group. There was a trend for participants who were able to monitor whenever they wished to be more likely to report receiving treatment than people who were only given information about their local treatment services. The impact of the intervention was greatest among participants who intended to seek treatment before taking part. Limitations were that only a small minority of those who downloaded the app completed the study and that the study relied on self-reported measures of treatment-seeking. Conclusions: Symptom monitoring can increase actual treatment-seeking in those with an intention to seek treatment.
Transcatheter right ventricle decompression in neonates with pulmonary atresia and intact ventricular septum is technically challenging, with risk of cardiac perforation and death. Further, despite successful right ventricle decompression, re-intervention on the pulmonary valve is common. The association between technical factors during right ventricle decompression and the risks of complications and re-intervention are not well described.
Methods
This is a multicentre retrospective study among the participating centres of the Congenital Catheterization Research Collaborative. Between 2005 and 2015, all neonates with pulmonary atresia and intact ventricular septum and attempted transcatheter right ventricle decompression were included. Technical factors evaluated included the use and characteristics of radiofrequency energy, maximal balloon-to-pulmonary valve annulus ratio, infundibular diameter, and right ventricle systolic pressure pre- and post-valvuloplasty (BPV). The primary end point was cardiac perforation or death; the secondary end point was re-intervention.
Results
A total of 99 neonates underwent transcatheter right ventricle decompression at a median of 3 days (IQR 2–5) of age, including 63 patients by radiofrequency and 32 by wire perforation of the pulmonary valve. There were 32 complications including 10 (10.5%) cardiac perforations, of which two resulted in death. Cardiac perforation was associated with the use of radiofrequency (p=0.047), longer radiofrequency duration (3.5 versus 2.0 seconds, p=0.02), and higher maximal radiofrequency energy (7.5 versus 5.0 J, p<0.01) but not with patient weight (p=0.09), pulmonary valve diameter (p=0.23), or infundibular diameter (p=0.57). Re-intervention was performed in 36 patients and was associated with higher post-intervention right ventricle pressure (median 60 versus 50 mmHg, p=0.041) and residual valve gradient (median 15 versus 10 mmHg, p=0.046), but not with balloon-to-pulmonary valve annulus ratio, atmospheric pressure used during BPV, or the presence of a residual balloon waist during BPV. Re-intervention was not associated with any right ventricle anatomic characteristics, including pulmonary valve diameter.
Conclusion
Technical factors surrounding transcatheter right ventricle decompression in pulmonary atresia and intact ventricular septum influence the risk of procedural complications but not the risk of future re-intervention. Cardiac perforation is associated with the use of radiofrequency energy, as well as radiofrequency application characteristics. Re-intervention after right ventricle decompression for pulmonary atresia and intact ventricular septum is common and relates to haemodynamic measures surrounding initial BPV.
We report the discovery in the Greenland ice sheet of a discrete layer of free nanodiamonds (NDs) in very high abundances, implying most likely either an unprecedented influx of extraterrestrial (ET) material or a cosmic impact event that occurred after the last glacial episode. From that layer, we extracted n-diamonds and hexagonal diamonds (lonsdaleite), an accepted ET impact indicator, at abundances of up to about 5×106 times background levels in adjacent younger and older ice. The NDs in the concentrated layer are rounded, suggesting they most likely formed during a cosmic impact through some process similar to carbon-vapor deposition or high-explosive detonation. This morphology has not been reported previously in cosmic material, but has been observed in terrestrial impact material. This is the first highly enriched, discrete layer of NDs observed in glacial ice anywhere, and its presence indicates that ice caps are important archives of ET events of varying magnitudes. Using a preliminary ice chronology based on oxygen isotopes and dust stratigraphy, the ND-rich layer appears to be coeval with ND abundance peaks reported at numerous North American sites in a sedimentary layer, the Younger Dryas boundary layer (YDB), dating to 12.9 ± 0.1 ka. However, more investigation is needed to confirm this association.
In the current manuscript, we provide an overview of a research program at the University of Georgia's Center for Family Research designed to expand upon rapid and ongoing developments in the fields of genetics and epigenetics. By placing those developments in the context of translational research on family and community determinants of health and well-being among rural African Americans, we hope to identify novel, modifiable environments and biological processes. In the first section of the article, we review our earlier work on genotypic variation effects on the association between family context and mental and physical health outcomes as well as differential responses to family-based intervention. We then transition to discuss our more recent research on the association of family and community environments with epigenetic processes. In this second section of the article, we begin by briefly reviewing terminology and basic considerations before describing evidence that early environments may influence epigenetic motifs that potentially serve as mediators of long-term effects of early family and community environments on longer term health outcomes. We also provide evidence that genotype may sometimes influence epigenetic outcomes. Finally, we describe our recent efforts to use genome-wide characterization of epigenetic patterns to better understand the biological impact of protective parenting on long-term shifts in inflammatory processes and its potential implications for young adult health. As will be clear, research on epigenetics as a mediator of the connections between family/community processes and a range of health outcomes is still in its infancy, but the potential to develop important insights regarding mechanisms linking modifiable environments to biological processes and long-term health outcomes already is coming into view.