Summary Background A third of all kidneys from deceased donors in the UK are donated after cardiac death, but concerns have been raised about the long-term outcome of such transplants. We aimed to ...establish these outcomes for kidneys donated after controlled cardiac death versus brain death, and to identify the factors that affect graft survival and function. Methods We used data from the UK transplant registry to select a cohort of deceased kidney donors and the corresponding transplant recipients (aged ≥18 years) for transplantations done between Jan 1, 2000, and Dec 31, 2007. Kaplan-Meier estimates were used to assess graft survival, and multivariate analyses were used to identify factors associated with graft survival and with long-term renal function, which was measured from estimated glomerular filtration rate (eGFR). Findings 9134 kidney transplants were done in 23 centres; 8289 kidneys were donated after brain death and 845 after controlled cardiac death. First-time recipients of kidneys from cardiac-death donors (n=739) or brain-death donors (n=6759) showed no difference in graft survival up to 5 years (hazard ratio 1·01, 95% CI 0·83 to 1·19, p=0·97), or in eGFR at 1–5 years after transplantation (at 12 months −0·36 mL/min per 1·73 m2 , 95% CI −2·00 to 1·27, p=0·66). For recipients of kidneys from cardiac-death donors, increasing age of donor and recipient, repeat transplantation, and cold ischaemic time of more than 12 h were associated with worse graft survival; grafts from cardiac-death donors that were poorly matched for HLA had an association with inferior outcome that was not significant, and delayed graft function and warm ischaemic time had no effect on outcome. Interpretation Kidneys from controlled cardiac-death donors provide good graft survival and function up to 5 years in first-time recipients, and are equivalent to kidneys from brain-death donors. Allocation policy for kidneys from cardiac-death donors should reduce cold ischaemic time, avoid large age mismatches between donors and recipients, and restrict use of kidneys poorly matched for HLA in young recipients. Funding UK National Health Service Blood and Transplant, and Cambridge National Institute for Health Research Biomedical Research Centre.
Abstract Background Image-based renal morphometry scoring systems are used to predict the potential difficulty of partial nephrectomy (PN), but they are centered entirely on tumor-specific factors ...and neglect other patient-specific factors that may complicate the technical aspects of PN. Adherent perinephric fat (APF) is one such factor known to make PN difficult. Objective To develop an accurate image-based nephrometry scoring system to predict the presence of APF encountered during robot-assisted partial nephrectomy (RAPN). Design, setting, and participants We prospectively analyzed 100 consecutive RAPNs performed by one surgeon and defined APF as the need for subcapsular renal dissection to isolate the renal tumor for RAPN. Outcome measurements and statistical analysis The scoring algorithm to predict the presence of APF was developed with a multivariable logistic regression model using a forward selection approach with a focus on improvement in the area under the receiver operating characteristic curve. Results and limitations Thirty patients (30%; 95% confidence interval, 21–40) had APF. Single-variable analysis noted an increased likelihood of APF in male patients ( p < 0.001), higher body mass index ( p = 0.003), greater posterior perinephric fat thickness ( p < 0.001), greater lateral perinephric fat thickness ( p < 0.001), and those with perirenal fat stranding ( p < 0.001). Two of these variables, posterior perinephric fat thickness and stranding, were most highly predictive of APF in multivariable analysis and were therefore used to create a risk score, termed Mayo Adhesive Probability (MAP) and ranging from 0 to 5, to predict the presence of APF. We observed APF in 6% of patients with a MAP score of 0, 16% with a score of 1, 31% with a score of 2, 73% with a score of 3–4, and 100% of patients with a score of 5. Conclusions MAP score accurately predicts the presence of APF in patients undergoing RAPN. Prospective validation of the MAP score is required. Patient summary The Mayo Adhesive Probability score that we we developed is an accurate system that predicts whether or not adherent perinephric, or “sticky,” fat is present around the kidney that would make partial nephrectomy difficult.
Releasing sterile or incompatible male insects is a proven method of population management in agricultural systems with the potential to revolutionize mosquito control. Through a collaborative ...venture with the "Debug" Verily Life Sciences team, we assessed the incompatible insect technique (IIT) with the mosquito vector
in northern Australia in a replicated treatment control field trial. Backcrossing a US strain of
carrying
AlbB from
with a local strain, we generated a
AlbB2-F4 strain incompatible with both the wild-type (no
) and
Mel-
now extant in North Queensland. The
AlbB2-F4 strain was manually mass reared with males separated from females using Verily sex-sorting technologies to obtain no detectable female contamination in the field. With community consent, we delivered a total of three million IIT males into three isolated landscapes of over 200 houses each, releasing ∼50 males per house three times a week over 20 wk. Detecting initial overflooding ratios of between 5:1 and 10:1, strong population declines well beyond 80% were detected across all treatment landscapes when compared to controls. Monitoring through the following season to observe the ongoing effect saw one treatment landscape devoid of adult
early in the season. A second landscape showed reduced adults, and the third recovered fully. These encouraging results in suppressing both wild-type and
Mel-
confirms the utility of bidirectional incompatibility in the field setting, show the IIT to be robust, and indicate that the removal of this arbovirus vector from human-occupied landscapes may be achievable.
Genetic analysis was applied to different regions of renal-cell cancers. The lesions noted in the tumor were not found in every sample, and regions of the tumor had different gene-expression ...patterns. This suggests that extrapolation from results of a single biopsy may be problematic.
Large-scale sequencing analyses of solid cancers have identified extensive heterogeneity between individual tumors.
1
–
6
Genetic intratumor heterogeneity has also been shown
7
–
15
and can contribute to treatment failure and drug resistance. Intratumor heterogeneity may have important consequences for personalized-medicine approaches that commonly rely on single tumor-biopsy samples to portray tumor mutational landscapes. Studies comparing mutational profiles of primary tumors and associated metastatic lesions
16
,
17
or local recurrences
18
have provided evidence of intratumor heterogeneity at nucleotide resolution. Intratumor heterogeneity within primary tumors and associated metastatic sites has not been systematically characterized by next-generation sequencing. We applied exome sequencing, chromosome aberration analysis, . . .
Significance
Goats were among the first domestic animals and today are an important livestock species; archaeozoological evidence from the Zagros Mountains of western Iran indicates that goats were ...managed by the late ninth/early eighth millennium. We assess goat assemblages from Ganj Dareh and Tepe Abdul Hosein, two Aceramic Neolithic Zagros sites, using complementary archaeozoological and archaeogenomic approaches. Nuclear and mitochondrial genomes indicate that these goats were genetically diverse and ancestral to later domestic goats and already distinct from wild goats. Demographic profiles from bone remains, differential diversity patterns of uniparental markers, and presence of long runs of homozygosity reveal the practicing and consequences of management, thus expanding our understanding of the beginnings of animal husbandry.
The Aceramic Neolithic (∼9600 to 7000 cal BC) period in the Zagros Mountains, western Iran, provides some of the earliest archaeological evidence of goat (
Capra hircus
) management and husbandry by circa 8200 cal BC, with detectable morphological change appearing ∼1,000 y later. To examine the genomic imprint of initial management and its implications for the goat domestication process, we analyzed 14 novel nuclear genomes (mean coverage 1.13X) and 32 mitochondrial (mtDNA) genomes (mean coverage 143X) from two such sites, Ganj Dareh and Tepe Abdul Hosein. These genomes show two distinct clusters: those with domestic affinity and a minority group with stronger wild affinity, indicating that managed goats were genetically distinct from wild goats at this early horizon. This genetic duality, the presence of long runs of homozygosity, shared ancestry with later Neolithic populations, a sex bias in archaeozoological remains, and demographic profiles from across all layers of Ganj Dareh support management of genetically domestic goat by circa 8200 cal BC, and represent the oldest to-this-date reported livestock genomes. In these sites a combination of high autosomal and mtDNA diversity, contrasting limited Y chromosomal lineage diversity, an absence of reported selection signatures for pigmentation, and the wild morphology of bone remains illustrates domestication as an extended process lacking a strong initial bottleneck, beginning with spatial control, demographic manipulation via biased male culling, captive breeding, and subsequently phenotypic and genomic selection.
Pulmonary hypertension is a complex disease with multiple causes, corresponding to phenotypic heterogeneity and variable therapeutic responses. Advancing understanding of pulmonary hypertension ...pathogenesis is likely to hinge on integrated methods that leverage data from health records, imaging, novel molecular -omics profiling, and other modalities. In this review, we summarize key data sets generated thus far in the field and describe analytical methods that hold promise for deciphering the molecular mechanisms that underpin pulmonary vascular remodeling, including machine learning, network medicine, and functional genetics. We also detail how genetic and subphenotyping approaches enable earlier diagnosis, refined prognostication, and optimized treatment prediction. We propose strategies that identify functionally important molecular pathways, bolstered by findings across multi-omics platforms, which are well-positioned to individualize drug therapy selection and advance precision medicine in this highly morbid disease.
Abstract
We conduct a systematic tidal disruption event (TDE) demographics analysis using the largest sample of optically selected TDEs. A flux-limited, spectroscopically complete sample of 33 TDEs ...is constructed using the Zwicky Transient Facility over 3 yr (from 2018 October to 2021 September). We infer the black hole (BH) mass (
M
BH
) with host galaxy scaling relations, showing that the sample
M
BH
ranges from 10
5.1
M
⊙
to 10
8.2
M
⊙
. We developed a survey efficiency corrected maximum volume method to infer the rates. The rest-frame
g
-band luminosity function can be well described by a broken power law of
ϕ
(
L
g
)
∝
L
g
/
L
bk
0.3
+
L
g
/
L
bk
2.6
−
1
, with
L
bk
= 10
43.1
erg s
−1
. In the BH mass regime of 10
5.3
≲ (
M
BH
/
M
⊙
) ≲ 10
7.3
, the TDE mass function follows
ϕ
(
M
BH
)
∝
M
BH
−
0.25
, which favors a flat local BH mass function (
dn
BH
/
d
log
M
BH
≈
constant
). We confirm the significant rate suppression at the high-mass end (
M
BH
≳ 10
7.5
M
⊙
), which is consistent with theoretical predictions considering direct capture of hydrogen-burning stars by the event horizon. At a host galaxy mass of
M
gal
∼ 10
10
M
⊙
, the average optical TDE rate is ≈3.2 × 10
−5
galaxy
−1
yr
−1
. We constrain the optical TDE rate to be 3.7, 7.4, and 1.6 × 10
−5
galaxy
−1
yr
−1
in galaxies with red, green, and blue colors.
BACKGROUNDDelayed graft function (DGF) after renal transplantation can be diagnosed according to several different definitions, complicating comparison between studies that use DGF as an endpoint. ...This is a particular problem after transplantation with kidneys from donation after circulatory death (DCD) kidneys, because DGF is common, and its relationship to early graft failure may differ depending on the definition of DGF.
METHODSThe presence of DGF in 213 donation after brain death (DBD) and 312 DCD kidney transplants from October 2005 to August 2011 was determined according to 10 different, but widely used, definitions (based on dialysis requirements, creatinine changes, or both). The relationship of DGF to graft function and graft survival was determined.
RESULTSThe incidence of DGF varied widely depending on the definition used (DBD; 24%–70%DCD; 41%–91%). For kidneys from DCD donors, development of DGF was only associated with poorer 1-year estimated glomerular filtration rate for 1 of 10 definitions of DGF, and no definition of DGF was associated with impaired graft survival. Conversely, for DBD kidneys, DGF, as defined in 9 of 10 different ways, was associated with poorer 1-year estimated glomerular filtration rate and inferior graft survival. Importantly, the predictive power for poorer transplant outcome was comparable for all definitions of DGF.
CONCLUSIONNo definition of DGF is superior. We suggest that the most widely used and most easily calculated definition—the use of dialysis in the first postoperative week—should be universally adopted as the definition of DGF clinically and as a study endpoint.
Based on rodent models, researchers have theorized that the hippocampus supports episodic memory and navigation via the theta oscillation, a ~4-10 Hz rhythm that coordinates brain-wide neural ...activity. However, recordings from humans have indicated that hippocampal theta oscillations are lower in frequency and less prevalent than in rodents, suggesting interspecies differences in theta's function. To characterize human hippocampal theta, we examine the properties of theta oscillations throughout the anterior-posterior length of the hippocampus as neurosurgical subjects performed a virtual spatial navigation task. During virtual movement, we observe hippocampal oscillations at multiple frequencies from 2 to 14 Hz. The posterior hippocampus prominently displays oscillations at ~8-Hz and the precise frequency of these oscillations correlates with the speed of movement, implicating these signals in spatial navigation. We also observe slower ~3 Hz oscillations, but these signals are more prevalent in the anterior hippocampus and their frequency does not vary with movement speed. Our results converge with recent findings to suggest an updated view of human hippocampal electrophysiology. Rather than one hippocampal theta oscillation with a single general role, high- and low-frequency theta oscillations, respectively, may reflect spatial and non-spatial cognitive processes.
Methodological issues relevant to magnetic resonance imaging studies of brain anatomy are discussed along with the findings on the neuroanatomic changes during childhood and adolescence. The ...development of the brain is also discussed.
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