The Rosetta de novo structure prediction and loop modeling protocols begin with coarse grained Monte Carlo searches in which the moves are based on short fragments extracted from a database of known ...structures. Here we describe a new object oriented program for picking fragments that greatly extends the functionality of the previous program (nnmake) and opens the door for new approaches to structure modeling. We provide a detailed description of the code design and architecture, highlighting its modularity, and new features such as extensibility, total control over the fragment picking workflow and scoring system customization. We demonstrate that the program provides at least as good building blocks for ab-initio structure prediction as the previous program, and provide examples of the wide range of applications that are now accessible.
Objective Lung cancer is the leading cause of cancer death in North America. Low-dose computed tomography screening can reduce lung cancer–specific mortality by 20%. Method The American Association ...for Thoracic Surgery created a multispecialty task force to create screening guidelines for groups at high risk of developing lung cancer and survivors of previous lung cancer. Results The American Association for Thoracic Surgery guidelines call for annual lung cancer screening with low-dose computed tomography screening for North Americans from age 55 to 79 years with a 30 pack-year history of smoking. Long-term lung cancer survivors should have annual low-dose computed tomography to detect second primary lung cancer until the age of 79 years. Annual low-dose computed tomography lung cancer screening should be offered starting at age 50 years with a 20 pack-year history if there is an additional cumulative risk of developing lung cancer of 5% or greater over the following 5 years. Lung cancer screening requires participation by a subspecialty-qualified team. The American Association for Thoracic Surgery will continue engagement with other specialty societies to refine future screening guidelines. Conclusions The American Association for Thoracic Surgery provides specific guidelines for lung cancer screening in North America.
Background and purpose
Individuals with radiologically isolated syndrome (RIS) are at increased risk of converting to multiple sclerosis (MS). Early identification of later converters is crucial for ...optimal treatment decisions. The purpose of this study was to assess the predictive potential of optical coherence tomography (OCT) measures in individuals with RIS regarding conversion to MS.
Methods
This prospective observational cohort study included 36 individuals with RIS and 36 healthy controls recruited from two German MS centers. All individuals received baseline OCT and clinical examination and were longitudinally followed over up to 6 years. The primary outcome measure was the conversion to MS.
Results
During clinical follow‐up of 46 (26–58) months (median, 25%–75% interquartile range), eight individuals with RIS converted to MS. Individuals converting to MS showed a thinning of the peripapillary retinal nerve fiber layer (pRNFL) and the common ganglion cell and inner plexiform layer (GCIP) at baseline and during follow‐up. Individuals with a pRNFL of 99 µm or lower or a GCIP of 1.99 mm3 or lower were at a 7.5‐ and 8.0‐fold risk for MS conversion, respectively, compared to individuals with higher measures. After correction for other known risk factors, Cox proportional hazards regression revealed a hazard ratio of 1.08 for conversion to MS for each 1 µm decline in pRNFL.
Conclusions
Reduction of the pRNFL might be a novel and independent risk factor for conversion to MS in individuals with RIS. OCT might be useful for risk stratification and therapeutic decision‐making in individuals with RIS.
•Young age, working in healthcare or from home and own Covid-19 illness were consistent risk factors of mental ill-health during the pandemic.•Women, healthcare staff and young people experienced ...deteriorating mental health over time.•Time patterns in the perceived burden from Covid-19-/related measures were consistent with the timely sequence of restrictions and relaxations of governmental measures.•Depression and anxiety were at a very high levels and relatively stable across the first pandemic year (2020)•Domestic violence appeared to increase immediately after periods of hard lockdowns, and suicidal ideation was lowest during the second of two hard lockdowns.
There is accumulating evidence about detrimental impacts of the pandemic on population mental health, but knowledge on risk of groups specifically affected by the pandemic and variations across time is still limited.
We surveyed approximately n=1,000 Austrian residents in 12 waves between April and December 2020 (n=12,029). Outcomes were suicidal ideation (Beck Suicidal Ideation Scale), depressive symptoms (Patient Health Questionnaire-9), anxiety (Hospital Anxiety Depression Scale), and domestic violence. We also assessed the perceived burden from the pandemic. Demographic and Covid-19 specific occupational and morbidity-related variables were used to explain outcomes in multivariable regression analyses, controlling for well-established risk factors of mental ill-health, and variations over time were analyzed.
Young age, working in healthcare or from home, and own Covid-19 illness were consistent risk factors controlling for a wide range of known mental health risk factors. Time patterns in the perceived burden from Covid-19-related measures were consistent with the time sequence of restrictions and relaxations of governmental measures. Depressive and anxiety symptoms were relatively stable over time, with some increase of depression during the second phase of lockdowns. Domestic violence increased immediately after both hard lockdowns. Suicidal ideation decreased slightly over time, with a low during the second hard lockdown. Mental health indicators for women and young people showed some deterioration over time, whereas those reporting own Covid-19 illness improved.
Data from before the pandemic were not available.
Among mental health outcomes, increases in domestic violence and, to some smaller extent, depressive symptoms, appeared most closely related to the timing of hard lockdowns. Healthcare staff, individuals working from home, those with Covid-19, as well as young people and women are non-traditional risk groups who warrant heightened attention in prevention during and in the aftermath of the pandemic.
We present 1201 galaxies at 0.05 < z < 0.45 that host tidal features in the first ∼200 deg2 of imaging from the Hyper Suprime-Cam Subaru Strategic Program (HSC-SSP). We select these galaxies from a ...sample of 21,208 galaxies with spectroscopic redshifts drawn from the Sloan Digital Sky Survey (SDSS) spectroscopic campaigns. Of these galaxies, we identify 214 shell systems and 987 stream systems. For 575 of these systems, we are additionally able to measure the (g−i) colors of the tidal features. We find evidence for star formation in a subset of the streams, with the exception of streams around massive ellipticals, and find that stream host galaxies span the full range of stellar masses in our sample. Galaxies that host shells are predominantly red and massive: we find that observable shells form more frequently around ellipticals than around disk galaxies of the same stellar mass. Although the majority of the shells in our sample are consistent with being formed by minor mergers, 15% 4.4% of shell host galaxies have (g−i) colors as red as their host galaxy, consistent with being formed by major mergers. These "red shell" galaxies are preferentially aligned with the major axis of the host galaxy, as previously predicted from simulations. We suggest that although the bulk of the observable shell population originates from fairly minor mergers, which preferentially form shells that are not aligned with the major axis of the galaxy, major mergers produce a significant number of observable shells.
We present a multiline survey of the interstellar medium (ISM) in two
z
> 6 quasar host galaxies, PJ231−20 (
z
= 6.59) and PJ308−21 (
z
= 6.23), and their two companion galaxies. Observations were ...carried out using the Atacama Large (sub-)Millimeter Array (ALMA). We targeted 11 transitions including atomic fine-structure lines (FSLs) and molecular lines: NII
205 μm
, CI
369 μm
, CO (
J
up
= 7, 10, 15, 16), H
2
O 3
12
− 2
21
, 3
21
− 3
12
, 3
03
− 2
12
, and the OH
163 μm
doublet. The underlying far-infrared (FIR) continuum samples the Rayleigh-Jeans tail of the respective dust emission. By combining this information with our earlier ALMA CII
158 μm
observations, we explored the effects of star formation and black hole feedback on the ISM of the galaxies using the CLOUDY radiative transfer models. We estimated dust masses, spectral indexes, IR luminosities, and star-formation rates from the FIR continuum. The analysis of the FSLs indicates that the CII
158 μm
and CI
369 μm
emission arises predominantly from the neutral medium in photodissociation regions (PDRs). We find that line deficits agree with those of local luminous IR galaxies. The CO spectral line energy distributions (SLEDs) reveal significant high-
J
CO excitation in both quasar hosts. Our CO SLED modeling of the quasar PJ231−20 shows that PDRs dominate the molecular mass and CO luminosities for
J
up
≤ 7, while the
J
up
≥ 10 CO emission is likely driven by X-ray dissociation regions produced by the active galactic nucleus (AGN) at the very center of the quasar host. The
J
up
> 10 lines are undetected in the other galaxies in our study. The H
2
O 3
21
− 3
12
line detection in the same quasar places this object on the
L
H
2
O
−
L
TIR
relation found for low-
z
sources, thus suggesting that this water vapor transition is predominantly excited by IR pumping. Models of the H
2
O SLED and of the H
2
O-to-OH
163 μm
ratio point to PDR contributions with high volume and column density (
n
H
∼ 0.8 × 10
5
cm
−3
,
N
H
= 10
24
cm
−2
) in an intense radiation field. Our analysis suggests a less highly excited medium in the companion galaxies. However, the current data do not allow us to definitively rule out an AGN in these sources, as suggested by previous studies of the same objects. This work demonstrates the power of multiline studies of FIR diagnostics in order to dissect the physical conditions in the first massive galaxies emerging from cosmic dawn.
The iconic giraffe, an ecologically important browser, has shown a substantial decline in numbers across Africa since the 1990s. In Serengeti National Park, Tanzania, giraffes reached densities of ...1.5–2.6 individuals km⁻² in the 1970s coincident with a pulse of Acacia tree recruitment. However, despite continued increases in woody cover between the 1980s and the 2000s, giraffe recruitment and survival rates have declined and density has dropped to only 0.3–0.4 giraffes km⁻². We used a decision table to investigate how four extrinsic factors may have contributed to these declines: food supply, predation, parasites, and poaching, which have all been previously shown to limit Serengeti ungulate populations. Lower recruitment likely resulted from a reduction in diet quality, owing to the replacement of preferred trees with unpalatable species, while decreased adult survival resulted from illegal harvesting, which appears to have had a greater impact on giraffe populations bordering the western and northern Serengeti. The Serengeti giraffe population will likely persist at low-to-moderate densities until palatable tree species regain their former abundance. Leslie matrix models suggest that park managers should meanwhile redouble their efforts to reduce poaching, thereby improving adult survival.
Natural killer (NK) cells play critical roles in immune defense and reproduction, yet remain the most poorly understood major lymphocyte population. Because their activation is controlled by a ...variety of combinatorially expressed activating and inhibitory receptors, NK cell diversity and function are closely linked. To provide an unprecedented understanding of NK cell repertoire diversity, we used mass cytometry to simultaneously analyze 37 parameters, including 28 NK cell receptors, on peripheral blood NK cells from 5 sets of monozygotic twins and 12 unrelated donors of defined human leukocyte antigen (HLA) and killer cell immunoglobulin-like receptor (KIR) genotype. This analysis revealed a remarkable degree of NK cell diversity, with an estimated 6000 to 30,000 phenotypic populations within an individual and >100,000 phenotypes in the donor panel. Genetics largely determined inhibitory receptor expression, whereas activation receptor expression was heavily environmentally influenced. Therefore, NK cells may maintain self-tolerance through strictly regulated expression of inhibitory receptors while using adaptable expression patterns of activating and costimulatory receptors to respond to pathogens and tumors. These findings further suggest the possibility that discrete NK cell subpopulations could be harnessed for immunotherapeutic strategies in the settings of infection, reproduction, and transplantation.
Purpose
This study assessed the clinical and immunological outcomes of SARS-CoV-2-infected patients with risk factors for severe disease depending on their immunological status.
Methods
In this ...retrospective study with single follow-up visit, clinical outcome and humoral immunity was monitored in SARS-CoV-2 infected patients at risk. The results were compared based on the patients’ initial immunological status: unvaccinated (UV), patients who did not develop neutralizing antibodies after vaccination (vaccine non-responders, VNR), and patients who expressed neutralizing antibodies after vaccination (vaccine responders, VR). Patients who lacked neutralizing antibodies (VNR and UV) were treated with nMABs.
Results
In total, 113 patients at risk of severe COVID-19 consented to participate in the study. VR and UV were not admitted to the hospital. During the observation period, UVs had the highest rate of SARS-CoV-2 re-infections. Three of 41 VNRs (7.3%) were hospitalized due to severe COVID-19, with two of them having undergone iatrogenic B-cell depletion. The humoral immune response after infection was significantly lower in the VNR group than in the VR group in terms of anti-N, anti-receptor-binding domain (RBD), anti-S antibody titers, and anti-S antibody avidity. In a sub-analysis of VNR, B cell-deficient non-responders had significantly lower levels of anti-N antibodies and anti-S avidity after infection than other VNRs.
Conclusion
VNR, particularly B-cell-depleted VNR, remained at risk of hospitalization due to COVID-19. In the VR group, however, no clinical complications or severe disease were observed, despite not receiving nMAbs. Tailoring the administration of nMABs according to patient vaccination and immunological status may be advisable.
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