Cryptic species are a challenge for systematics, but their elucidation also may leave critical information gaps about the distribution, conservation status, and behavior of affected species. We use ...the leopard frogs of the eastern U.S. as a case study of this issue. We refined the known range of the recently described Rana kauffeldi, the Atlantic Coast Leopard Frog, relative to the region's two other leopard frog species, conducted assessments of conservation status, and improved methods for separating the three species using morphological field characters. We conducted over 2,000 call and visual surveys and took photographs of and tissue samples from hundreds of frogs. Genetic analysis supported a three-species taxonomy and provided determinations for 220 individual photographed frogs. Rana kauffeldi was confirmed in eight U.S. states, from North Carolina to southern Connecticut, hewing closely to the Atlantic Coastal Plain. It can be reliably differentiated in life from R. pipiens, and from R. sphenocephala 90% of the time, based on such characters as the femoral reticulum patterning, dorsal spot size and number, and presence of a snout spot. However, the only diagnostic character separating R. kauffeldi from R. sphenocephala remains the breeding call described in 2014. Based on our field study, museum specimens, and prior survey data, we suggest that R. kauffeldi has declined substantially in the northern part of its range, but is more secure in the core of its range. We also report, for the first time, apparent extirpations of R. pipiens from the southeastern portion of its range, previously overlooked because of confusion with R. kauffeldi. We conclude with a generalized ecological research agenda for cryptic species. For R. kauffeldi, needs include descriptions of earlier life stages, studies of niche partitioning with sympatric congeners and the potential for hybridization, and identification of conservation actions to prevent further declines.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Background
As part of a randomized phase II trial in patients with isolated resectable colorectal peritoneal metastases (CPMs), the present study compared patient-reported outcomes (PROs) of patients ...treated with perioperative systemic therapy versus cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS–HIPEC) alone. Also, PROs of patients receiving perioperative systemic therapy were explored.
Patients and Methods
Eligible patients were randomized to perioperative systemic therapy (experimental) or CRS–HIPEC alone (control). PROs were assessed using EORTC QLQ-C30, QLQ-CR29, and EQ-5D-5L questionnaires at baseline, after neoadjuvant treatment (experimental), and at 3 and 6 months postoperatively. Linear mixed modeling was used to compare five predefined PROs (visual analog scale, global health status, physical functioning, fatigue, C30 summary score) between arms and to longitudinally analyze PROs in the experimental arm.
Results
Of 79 analyzed patients, 37 (47%) received perioperative systemic therapy. All predefined PROs were comparable between arms at all timepoints and returned to baseline at 3 or 6 months postoperatively. The experimental arm had worsening of fatigue mean difference (MD) + 14,
p
= 0.001, loss of appetite (MD + 15,
p
= 0.003), hair loss (MD + 18,
p
< 0.001), and loss of taste (MD + 27,
p
< 0.001) after neoadjuvant treatment. Except for loss of appetite, these PROs returned to baseline at 3 or 6 months postoperatively.
Conclusions
In patients with resectable CPM randomized to perioperative systemic therapy or CRS–HIPEC alone, PROs were comparable between arms and returned to baseline postoperatively. Together with the trial’s previously reported feasibility and safety data, these findings show acceptable tolerability of perioperative systemic therapy in this setting.
Primary melanocytic neoplasms of the central nervous system (CNS) consist of a spectrum ranging from well-differentiated melanocytoma to its overtly malignant counterpart, melanoma. Diagnostically ...difficult intermediate lesions lie between these extremes. Clinicopathologic features of 33 cases were studied to define histologic appearances, diagnostic criteria, and the clinical behavior of lesions along this spectrum. Seventeen cases were well-differentiated, solitary leptomeningeal tumors classified as melanocytomas. They contained variably pigmented melanocytic cells arranged in tight nests, sheets, or fascicles. Mitotic rates ranged from zero to one per 10 high-power fields (HPFs), with most having zero per 10 HPFs. All tumors were immunoreactive for HMB-45 and S-100 protein and negative for epithelial membrane antigen. MIB-1 staining was low (<1-2%). Nuclei were regular, often with small, eosinophilic nucleoli. These lesions arose predominantly in the spinal canal (65%) in patients ranging in age from 17 to 73 years. None recurred after surgical resection. In contrast to these benign lesions, there were 13 cases with histologic and cytologic features consistent with those of malignant melanoma. These cases contained larger, cytologically atypical, pigmented tumor cells growing in loose nests or sheets, often with CNS invasion or necrosis. Some contained bizarre, pleomorphic nuclei; others were densely cellular and mitotically active, but less pleomorphic. Mitotic rates (mean, 5.7 per 10 HPFs) and MIB-1 labeling indices (mean, 8.1%) were higher than those of melanocytomas. Melanomas occurred at spinal (38%), posterior fossa (38%), and supratentorial (23%) levels in patients ranging in age from 15 to 71 years. After resection, 8 of 13 lesions recurred, with four being fatal (mean survival, 14 months). Of five totally resected melanomas, four did not recur (mean follow-up, 26 months). Three intermediate-grade melanocytic tumors could not be classified as melanocytoma or melanoma. All showed sheetlike growth patterns, microscopic CNS invasion, and occasional mitoses. MIB-1 staining ranged from 1% to 4%. One tumor recurred after 17 months; one patient was lost to follow-up after 5 months; and the third died after surgery. Although melanocytic tumors represent a spectrum of lesions, certain histopathologic features are helpful in predicting biologic behavior.
•Additional information did not impact intentions to participate in CC screening.•Additional information increased uncertainty to seek precancer treatment in Norway.•Women reported strong ...system-specific preferences for sources of information.•Having a prior Pap-test was an important predictor of intentions-to-participate.•Socioeconomic factors influenced follow-up intentions in the U.S. but not in Norway.
We aimed to identify how additional information about benefits and harms of cervical cancer (CC) screening impacted intention to participate in screening, what type of information on harms women preferred receiving, from whom, and whether it differed between two national healthcare settings. We conducted a survey that randomized screen-eligible women in the United States (n = 1084) and Norway (n = 1060) into four groups according to the timing of introducing additional information. We found that additional information did not significantly impact stated intentions-to-participate in screening or follow-up testing in either country; however, the proportion of Norwegian women stating uncertainty about seeking precancer treatment increased from 7.9% to 14.3% (p = 0.012). Women reported strong system-specific preferences for sources of information: Norwegians (59%) preferred it come from a national public health agency while Americans (59%) preferred it come from a specialist care provider. Regression models revealed having a prior Pap-test was the most important predictor of intentions-to-participate in both countries, while having lower income reduced the probabilities of intentions-to-follow-up and seek precancer treatment among U.S. women. These results suggest that additional information on harms is unlikely to reduce participation in CC screening but could increase decision uncertainty to seek treatment. Providing unbiased information would improve on the ethical principle of respect for autonomy and self-determination. However, the clinical impact of additional information on women’s understanding of the trade-offs involved with CC screening should be investigated. Future studies should also consider country-specific socioeconomic barriers to screening if communication re-design initiatives aim to improve CC screening participation.
Highlights • Administration of AHS-LAV combinations can affect RNAemia level. • Length of time between AHS-LAV combinations can affect RNAemia level. • Use of AHS-LAV can complicate surveillance ...strategies. • Multiple AHSV types contained in AHS-LAVs can increase risk of reassortment.
Paediatric dolutegravir doses approved by stringent regulatory authorities (SRAs) for children weighing 20 kg to less than 40 kg until recently required 25 mg and 10 mg film-coated tablets. These ...tablets are not readily available in low-resource settings where the burden of HIV is highest. We did nested pharmacokinetic substudies in patients enrolled in the ODYSSEY-trial to evaluate simplified dosing in children with HIV.
We did pharmacokinetic and safety substudies within the open-label, multicentre, randomised ODYSSEY trial (NCT02259127) of children with HIV starting treatment in four research centres in Uganda and Zimbabwe. Eligible children were randomised to dolutegravir in ODYSSEY and weighed 20 kg to less than 40 kg. In children weighing 20 kg to less than 25 kg, we assessed dolutegravir's pharmacokinetics in children given once daily 25 mg film-coated tablets (approved by the SRAs at the time of the study) in part one of the study, and 50 mg film-coated tablets (adult dose) or 30 mg dispersible tablets in part two of the study. In children weighing 25 kg to less than 40 kg, we also assessed dolutegravir pharmacokinetics within-subject on film-coated tablet doses of 25 mg or 35 mg once daily, which were approved by the SRAs for the children's weight band; then switched to 50 mg film-coated tablets once daily. Steady-state 24 h dolutegravir plasma concentration-time pharmacokinetic profiling was done in all enrolled children at baseline and 1, 2, 3, 4, 6, and 24 h after observed dolutegravir intake. Target dolutegravir trough concentrations (Ctrough) were based on reference adult pharmacokinetic data and safety was evaluated in all children in the corresponding weight bands who consented to pharmacokinetic studies and received the studied doses.
Between Sept 22, 2016, and May 31, 2018, we enrolled 62 black-African children aged from 6 years to younger than 18 years (84 pharmacokinetic-profiles). In children weighing 20 kg to less than 25 kg taking 25 mg film-coated tablets, the geometric mean (GM) Ctrough (coefficient of variation) was 0·32 mg/L (94%), which was 61% lower than the GM Ctrough of 0·83 mg/L (26%) in fasted adults on dolutegravir 50 mg once-daily; in children weighing 25 kg to less than 30 kg taking 25 mg film-coated tablets, the GM Ctrough was 0·39 mg/L (48%), which was 54% lower than the GM Ctrough in fasted adults; and in those 30 kg to less than 40 kg taking 35 mg film-coated tablets the GM Ctrough was 0·46 mg/L (63%), which was 45% lower than the GM Ctrough in fasted adults. On 50 mg film-coated tablets or 30 mg dispersible tablets, Ctrough was close to the adult reference (with similar estimates on the two formulations in children in the 20 to <25 kg weight band), with total exposure (area under the concentration-time curve from 0 h to 24 h) in between reference values in adults dosed once and twice daily, where safety data are reassuring, although maximum concentrations were higher in children weighing 20 kg to less than 25 kg than in the twice-daily adult reference. Over a 24-week follow-up period in 47 children on 30 mg dispersible tablets or 50 mg film-coated tablets, none of the three reported adverse events (cryptococcal meningitis, asymptomatic anaemia, and asymptomatic neutropenia) were considered related to dolutegravir.
Adult dolutegravir 50 mg film-coated tablets given once daily provide appropriate pharmacokinetic profiles in children weighing 20 kg or more, with no safety signal, allowing simplified practical dosing and rapid access to dolutegravir. These results informed the WHO 2019 dolutegravir paediatric dosing guidelines and have led to US Food and Drug Administration approval of adult dosing down to 20 kg.
Paediatric European Network for Treatment of AIDS Foundation, ViiV Healthcare, UK Medical Research Council.
Using ion–electron fluid parameters derived from Cassini Plasma Spectrometer (CAPS) observations within Saturn's inner magnetosphere as presented in Sittler et al. 2006a. Cassini observations of ...Saturn's inner plasmasphere: Saturn orbit insertion results. Planet. Space Sci., 54, 1197–1210, one can estimate the ion total flux tube content,
N
ION
L
2, for protons, H
+, and water group ions, W
+, as a function of radial distance or dipole
L shell. In Sittler et al. 2005. Preliminary results on Saturn's inner plasmasphere as observed by Cassini: comparison with Voyager. Geophys. Res. Lett. 32(14), L14S04), it was shown that protons and water group ions dominated the plasmasphere composition. Using the ion–electron fluid parameters as boundary condition for each
L shell traversed by the Cassini spacecraft, we self-consistently solve for the ambipolar electric field and the ion distribution along each of those field lines. Temperature anisotropies from Voyager plasma observations are used with
(
T
⊥
/
T
∥
)
W
+
∼
5
and
(
T
⊥
/
T
∥
)
H
+
∼
2
. The radio and plasma wave science (RPWS) electron density observations from previous publications are used to indirectly confirm usage of the above temperature anisotropies for water group ions and protons. In the case of electrons we assume they are isotropic due to their short scattering time scales. When the above is done, our calculation show
N
ION
L
2 for H
+ and W
+ peaking near Dione's
L shell with values similar to that found from Voyager plasma observations. We are able to show that water molecules are the dominant source of ions within Saturn's inner magnetosphere. We estimate the ion production rate
S
ION∼10
27
ions/s as function of dipole
L using
N
H
+
,
N
W
+
and the time scale for ion loss due to radial transport
τ
D
and ion–electron recombination
τ
REC. The ion production shows localized peaks near the
L shells of Tethys, Dione and Rhea, but not Enceladus. We then estimate the neutral production rate,
S
W, from our ion production rate,
S
ION, and the time scale for loss of neutrals by ionization,
τ
ION, and charge exchange,
τ
CH. The estimated source rate for water molecules shows a pronounced peak near Enceladus’
L shell
L∼4, with a value
S
W∼2×10
28
mol/s.
Considering a noncentrosymmetric pinning texture composed of a square array of triangular holes, the magnetic flux penetration and expulsion are investigated experimentally and theoretically. A ...direct visualization of the magnetic landscape obtained using a magneto-optical technique on a Nb film is complemented by a multiscale numerical modeling. This combined approach allows the magnetic flux dynamics to be identified from the single flux quantum limit up to the macroscopic electromagnetic response. Within the theoretical framework provided by time-dependent Ginzburg-Landau simulations, an estimation of the in-plane current anisotropy is obtained and its dependence with the radius of the curvature of hole vertices is addressed. These simulations show that current crowding plays an important role in channeling the flux motion, favoring hole-to-hole flux hopping rather than promoting interstitial flux displacement in between the holes. The resulting anisotropy of the critical current density gives rise to a distinct pattern of discontinuity lines for increasing and decreasing applied magnetic fields, in sharp contrast to the invariable patterns reported for centrosymmetric pinning potentials. This observation is partially accounted for by the rectification effect, as demonstrated by finite-element modeling. At low temperatures, where magnetic field penetration is dominated by thermomagnetic instabilities, highly directional magnetic flux avalanches with a fingerlike shape are observed to propagate along the easy axis of the pinning potential. This morphology is reproduced by numerical simulations. Our findings demonstrate that anisotropic pinning landscapes and, in particular, ratchet potentials produce subtle modifications to the critical state field profile that are reflected in the distribution of discontinuity lines.
Display omitted
•Topsoil SOC stocks and soil structure recovered 26 years after topsoil removal.•Topsoil buried under the plough layer non-linearly lost 30–50% of SOC in 55 years.•Topsoil SOC ...recovery and stability of buried SOC was dependent on N fertilisation.
Erosion of fertile topsoil means severe land degradation and yield loss. Here, we show that reformation of the fertile topsoil and crop yield increase is possible by good agricultural management within a few decades. Evidence relies on a unique long-term field experiment in NE Germany, where in 1964 the sandy soil (Luvisol) had been excavated to 52 cm and refilled with subsoil material of 52 cm thickness. Undisturbed trials served as controls, these were all combined with either no fertilisation, mineral fertilisation or a combined mineral and organic fertilisation. It took only 26 years until new topsoil had been formed. Its soil organic carbon (SOC) and total N stocks and the aggregate size distributions equalled that of the other treatments; SOC sequestration corresponded to 28 Mg SOC ha−1. The former topsoil buried below the plough layer lost 30–50 percent of its SOC during 5 decades in a non-linear manner. We conclude that our current agricultural tools can restore degraded arable land rather fast and contribute to climate change mitigation through a significant SOC sequestration as well.
A certain number of anatomic variants involving the distal vertebral artery (VA) are explained by variations in size and connection of the lateral spinal artery (LSA). This study examined the ...possible role of another branch of the VA, the posterior spinal artery (PSA), in the development of similar vascular variations.
Four types of variations in the distal VA, including the C1 and C2 origins of the posterior inferior cerebellar artery (PICA), the duplication of the distal VA, and the aberrant course of the distal VA, are illustrated by 9 angiographic observations.
For each type of VA variant listed above, examples resulting from variations in size and connection of the LSA and PSA could be matched.
Variation in size and connection of the PSA is at the origin of a set of anatomic variations of the distal VA similar, but not identical, to the vascular variants linked to the LSA.
PDF
