An Assessment of Earth's Climate Sensitivity Using Multiple Lines of Evidence.

We assess evidence relevant to Earth's equilibrium climate sensitivity per doubling of atmospheric CO2, characterized by an effective sensitivity S. This evidence includes feedback process understanding, the historical climate record, and the paleoclimate record. An S value lower than 2 K is difficult to reconcile with any of the three lines of evidence. The amount of cooling during the Last Glacial Maximum provides strong evidence against values of S greater than 4.5 K. Other lines of evidence in combination also show that this is relatively unlikely. We use a Bayesian approach to produce a probability density function (PDF) for S given all the evidence, including tests of robustness to difficult-to-quantify uncertainties and different priors. The 66% range is 2.6-3.9 K for our Baseline calculation and remains within 2.3-4.5 K under the robustness tests; corresponding 5-95% ranges are 2.3-4.7 K, bounded by 2.0-5.7 K (although such high-confidence ranges should be regarded more cautiously). This indicates a stronger constraint on S than reported in past assessments, by lifting the low end of the range. This narrowing occurs because the three lines of evidence agree and are judged to be largely independent and because of greater confidence in understanding feedback processes and in combining evidence. We identify promising avenues for further narrowing the range in S, in particular using comprehensive models and process understanding to address limitations in the traditional forcing-feedback paradigm for interpreting past changes.

An audit of the use of platelet transfusions at Universitas Academic Hospital, Bloemfontein, South Africa.

An audit was performed at a tertiary hospital in Bloemfontein, South Africa, to establish whether clinicians adhered to local platelet transfusion guidelines. The audit showed poor compliance with local guidelines, with 34% of platelet transfusions not aligned with guidelines and 29.9% of transfusions administered to patients with platelet counts of ≥ 150 × 10(9)/L. When compared to medical disciplines, surgical disciplines tended significantly more to transfuse platelets inappropriately (17.1% and 53.7%, respectively; p < 0.0001). Documentation was poor and in 48.4% of orders for platelets, the indication for the platelet transfusion was not clearly stated. Considerable cost could be avoided with improved adherence to guidelines. This study emphasises the need for improving education in transfusion medicine amongst medical doctors. It is hoped that the information gleaned from this study would assist in the design of educational programmes in transfusion medicine as we attempt to close the existing gaps in knowledge and skills in the field, while ensuring that blood is transfused in a cost-effective and appropriate manner.

Patients' recall and perceptions regarding consent to blood transfusion at Universitas Academic Hospital, Bloemfontein, South Africa.

We studied the recall and perceptions of transfused patients at a single centre. Fifty-three patients were included. In 11 (20.8%) cases, no written informed consent document could be traced. Four patients who had informed consent documents in their records had no recollection of the consent process. Approximately 11% of patients stated that the consent process was performed using unfamiliar terms. When compared to Caucasian and mixed race respondents, more African respondents (83%) would have preferred the presence of a family member (p < 0.01). Although not all the patients experienced the informed consent positively, it did not impact on their perception of the blood transfusion itself.

Pityriasis rotunda as an incidental paraneoplastic finding in two patients with multiple myeloma.

Pityriasis rotunda (PR) is an uncommon chronic dermatosis, which may be idiopathic or may be associated with infections or malignancy. We describe the clinical and biochemical findings of two patients with multiple myeloma, who were incidentally diagnosed with PR, and detail the clinical conditions with which this rare paraneoplastic phenomenon may be associated. Although PR is a rare condition, it may be found as a paraneoplastic phenomenon in a range of conditions, and thus should be recognised as an important clinical sign.

Withdrawal of bevacizumab is associated with rebound growth of vestibular schwannomas in neurofibromatosis type 2-related schwannomatosis patients.

Background: Neurofibromatosis type 2 (NF2)-related schwannomatosis is an autosomal dominant tumor-predisposition syndrome characterized by bilateral vestibular schwannomas (VS). In patients with VS associated with NF2, vascular endothelial growth factor A inhibitor, bevacizumab, is a systemic treatment option. The aim of this study is to retrospectively evaluate NF2 patient responses to bevacizumab on VS growth and symptom progression. Methods: This is a retrospective analysis of patients seen at the Mayo Clinic Rochester Multidisciplinary NF2 Clinic. Results: Out of 76 patients with NF2 evaluated between 2020 and 2022, we identified 19 that received treatment with bevacizumab. Thirteen of these patients discontinued bevacizumab after median treatment duration of 12.2 months. The remaining 6 patients are currently receiving bevacizumab treatment for a median duration of 9.4 months as of March, 2023. Fifteen patients had evaluable brain MRI data, which demonstrated partial responses in 5 patients, stable disease in 8, and progression in 2. Within 6 months of bevacizumab discontinuation, 5 patients had rebound growth of their VS greater than 20% from their previous tumor volume, while 3 did not. Three patients with rebound growth went on to have surgery or irradiation for VS management. Conclusions: Our single-institution experience confirms prior studies that bevacizumab can control progression of VS and symptoms associated with VS growth. However, we note that there is the potential for rapid VS growth following bevacizumab discontinuation, for which we propose heightened surveillance imaging and symptom monitoring for at least 6 months upon stopping anti-VEGF therapy.

Cooling an acute muscle injury: can basic scientific theory translate into the clinical setting?

Ice is commonly used after acute muscle strains but there are no clinical studies of its effectiveness. By comparison, there are a number of basic scientific studies on animals which show that applying ice after muscle injury has a consistent effect on a number of important cellular and physiological events relating to recovery. Some of these effects may be temperature dependant; most animal studies induce significant reductions in muscle temperature at the injury site. The aim of this short report was to consider the cooling magnitudes likely in human models of muscle injury and to discuss its relevance to the clinical setting. Current best evidence shows that muscle temperature reductions in humans are moderate in comparison to most animal models, limiting direct translation to the clinical setting. Further important clinical questions arise when we consider the heterogenous nature of muscle injury in terms of injury type, depth and insulating adipose thickness. Contrary to current practice, it is unlikely that a 'panacea' cooling dose or duration exists in the clinical setting. Clinicians should consider that in extreme circumstances of muscle strain (eg, deep injury with high levels of adipose thickness around the injury site), the clinical effectiveness of cooling may be significantly reduced.

Influence of maternal protein restriction in primiparous heifers during mid- and/or late-gestation on meat quality and fatty acid profile of progeny.

The objective of this study was to evaluate the influence of metabolizable protein (MP) restriction in mid- and/or late-gestation on meat quality characteristics of progeny. Heifers were assigned to 2 levels of dietary protein (control [CON], 102% of MP requirements; or restricted [RES], 80% of MP requirements) at 2 stages of gestation (mid-gestation [MID] and late-gestation [LATE]) in a Balaam's Design crossover treatment structure resulting in 4 treatment combinations (CON-CON, CON-RES, RES-CON, RES-RES). A carryover effect of MID MP treatment on LATE CON indicated CON-CON steaks were more tender (P < .001) than RES CON. Mid-gestation restriction resulted in progeny with increased (P < .05) carcass water, soft tissue moisture, and decreased soft tissue fat percentage compared with progeny from dams receiving MID CON. Reduced maternal MP also differentially influenced the fatty acid profiles of progeny. Results suggest it is possible for progeny to overcome a moderate gestational MP restriction with minimal impacts on carcass composition or meat characteristics.

Concomitant HIV infection in newly diagnosed multiple myeloma patients is hard to recognise and should be tested for routinely in areas of high endemicity.

BACKGROUND: Over the past three decades much has changed in the treatment and outcomes of patients suffering concurrently from both multiple myeloma (MM) and HIV. While the prevalence of MM appears to be higher in HIV-positive individuals than in those who are uninfected, early recognition of patients suffering from both diseases is difficult and little information is available on their demographics and clinical presentation. OBJECTIVE: To compare the presenting features of HIV-positive patients diagnosed with MM with those of HIV-negative patients. METHODS: A single-centre, retrospective cohort study included 16 HIV-positive and 73 HIV-negative patients diagnosed with MM, in order to compare variables related to the clinical presentation of both conditions. RESULTS: HIV-positive patients presented with MM at a significantly younger age, and had fewer osteolytic lesions, less renal impairment and lower neutrophil counts. Disease stage, gender, pathological fractures, bone marrow plasmacytosis, plasmacytomas and lymphocyte counts were comparable, emphasising the difficulty of identifying these patients. The HIV-positive patients had relatively high CD4 counts and a low prevalence of abnormal Freelite kappa/lambda ratios. All HIV-positive patients presented with paraproteins of the immunoglobulin G (IgG) type, implying a possible relationship between MM and an IgG response to HIV antigens. CONCLUSIONS: On the basis of our findings and literature on the treatment of both diseases, we suggest that HIV be tested for routinely in younger MM patients, especially in areas with a high prevalence of HIV. The integration of our results into the sparse knowledge on the role of HIV infection-related MM provides possible new insights into the interaction between these diseases.

Effect of nursing-calf implant timing on growth performance and carcass characteristics.

The objective of this study was to compare pre- and postweaning growth performance, carcass characteristics, and meat quality attributes of calves that did not receive an implant or were implanted early or late in the nursing period. Crossbred steer calves ( = 135) were stratified by birth date and birth weight and randomly assigned to the following implant treatments: control (CON; no preweaning implant), 58 d (EARLY; 36 mg zeranol, administered at an average of 58 ± 13 d of age), and 121 d (LATE; 36 mg zeranol, administered at an average 121 ± 13 d of age). After weaning, steers were blocked by initial feed yard BW to 15 pens (5 pens/treatment and 9 steers/pen). All steers were implanted on d 21 after arrival at the feed yard and again on d 108 of finishing. Steer BW and ultrasound assessment of rib eye area (uREA), rib fat thickness (uRFT), and percent intramuscular fat (uIMF) were collected when implants were administered, at weaning, and on harvest day. Carcass measurements included HCW, rib eye area (REA), 12th-rib fat thickness (FT), and marbling score. Objective color (L*, a*, and b*) was recorded, and a 3.8-cm strip loin section was removed from both sides of each carcass and portioned into 2.54-cm steaks that were aged for 3 or 14 d for analysis of cook loss and Warner-Bratzler shear force (WBSF). The remaining portion of each sample was used for analysis of moisture and crude fat. Steer BW, ADG, and G:F did not differ among treatments ( > 0.05). Steers implanted in the EARLY treatment had a greater ( < 0.05) cumulative DMI than CON but were not different from steers implanted in the LATE treatment. Ultrasound REA and uRFT (averaged across all collection days) did not differ ( > 0.05); however, steers on the CON treatment had a greater ( ≤ 0.05) percent uIMF than EARLY implanted steers, whereas steers receiving the LATE implant were intermediate and not different from the other treatments. Hot carcass weight, REA, FT, USDA yield grade, marbling score, and objective color did not differ ( > 0.05) among treatments. The proportion of steers in each USDA yield and quality grade was similar ( > 0.05) among treatments, and no differences were detected for total carcass value or price per 45.4 kg (hundredweight; > 0.05). Treatment did not influence ( > 0.05) percent cook loss, crude fat, moisture, or WBSF. In conclusion, administering a nursing implant, regardless of timing, did not influence live performance, carcass characteristics, or meat quality of steers fed in this study.

Phase II evaluation of cytembena (NSC-104801) in patients with advanced ovarian carcinoma resistant to alkylating agents: brief communication.

Seventeen patients with stages III and IV alkylating agent-resistant ovarian carcinomas were treated with cytembena, which was given in doses of 200 mg/m2 twice daily for 5 consecutive days every 5 weeks. Sixteen patients completed at least one course of treatment; 11 of them experienced objective progression of disease or failed to continue treatment because of a continuing symptomatic deterioration within the first two treatment cycles. Three patients remained objectively stable after two courses of treatment, but were symptomatically worse and stopped treatment for that reason. Another patient experienced progression after three courses, and the final patient voluntarily withdrew after three courses. No objective regression of disease occurred during treatment with cytembena. Nausea and vomiting occurred at some time in all except 1 patient, and 3 patients experienced mild diarrhea. Two patients had alopecia.

Intraoperative radiation therapy in gynecologic cancer: update of the experience at a single institution.

PURPOSE: To update the Mayo Clinic experience with intraoperative radiation therapy (IORT) in patients with gynecologic cancer. METHODS AND MATERIALS: Between January 1983 and June 1991, 39 patients with recurrent or locally advanced gynecologic malignancies received intraoperative radiation therapy with electrons. The anatomical area treated was pelvis (side walls or presacrum) or periaortic nodes or a combination of both. In addition to intraoperative radiation therapy, 28 patients received external beam irradiation (median dose, 45 Gy; range, 0.9 to 65.7 Gy), and 13 received chemotherapy preoperatively. At the time of intraoperative radiation therapy and after maximum debulking operation, 23 patients had microscopic residual disease and 16 had gross residual disease up to 5 cm in thickness. Median follow-up for surviving patients was 43.4 months (range, 27.1 to 125.4 months). RESULTS: The 5-year actuarial local control with or without central control was 67.4%, and the control within the IORT field (central control) was 81%. The risk of distant metastases at 5 years was 52% (82% in patients with gross residual disease and 33% in patients with only microscopic disease postoperatively). Actuarial 5-year overall survival and disease-free survival was 31.5 and 40.5%, respectively. Patients with microscopic disease had 5-year disease-free and overall survival of 55 and 50%, respectively. Grade 3 toxicity was directly associated with IORT in six patients (15%). CONCLUSION: Patients with local, regionally recurrent gynecologic cancer may benefit from maximal surgical debulking and IORT with or without external beam irradiation, especially those with microscopic residual disease.

Spontaneous renal rupture during pregnancy.

Spontaneous rupture of the renal parenchyma or renal pelvis during pregnancy has been previously reported in 16 cases. In the case we describe in this report, the patient initially had right flank pain and nausea for 48 hours, which progressed to severe abdominal symptoms that necessitated exploratory laparotomy. Cystoscopic placement of a ureteral stent relieved the obstruction and allowed spontaneous healing of the renal pelvis. Dilatation of the urinary collecting system commonly occurs during pregnancy. Spontaneous rupture of the renal parenchyma or renal pelvis, however, is unusual and often associated with diseased kidneys. Our case is the 8th one of spontaneous rupture of the renal collecting system with no identifiable underlying pathologic condition and the 17th case of spontaneous renal rupture overall.

Blaschkolinear malformation syndrome in complex trisomy-7 mosaicism.

Results of repeated peripheral blood chromosome studies were normal in a boy with intrauterine growth retardation, short stature, moderate mental retardation, and multiple minor anomalies. At age 9 years it was recognized that the swirls of pigmentation/depigmentation on his trunk, linear streaks on his limbs, and body asymmetry were suggestive of chromosomal mosaicism. Four skin biopsies were obtained under anesthesia during a dental procedure. All showed mosaicism for a normal cell line, a line with an extra chromosome 7, and a cell line with an extra small ring. In one biopsy, there was a fourth cell line with an extra chromosome 7 and the ring. Fluorescence in situ hybridization (FISH) with a chromosome 7 paint confirmed trisomy 7 and the chromosome 7 derivation of the ring. This young man's intra-uterine and postnatal growth retardation is an aneuploidy effect, whereas his asymmetry reflects a mosaicism effect that should have aroused suspicion of tissue-limited mosaicism before the development of obvious Blaschkolinear skin pigmentary dysplasia.

Prenatal diagnosis of chromosome 15 abnormalities in the Prader-Willi/Angelman syndrome region by traditional and molecular cytogenetics.

With improvements in culturing and banding techniques, amniotic fluid studies now achieve a level of resolution at which the Prader-Willi syndrome (PWS) and Angelman syndrome (AS) region may be questioned. Chromosome 15 heteromorphisms, detected with Q- and R-banding and used in conjunction with PWS/AS region-specific probes, can confirm a chromosome deletion and establish origin to predict the clinical outcome. We report four de novo cases of an abnormal-appearing chromosome 15 in amniotic fluid samples referred for advanced maternal age or a history of a previous chromosomally abnormal child. The chromosomes were characterized using G-, Q-, and R-banding, as well as isotopic and fluorescent in situ hybridization of DNA probes specific for the proximal chromosome 15 long arm. In two cases, one chromosome 15 homolog showed a consistent deletion of the ONCOR PWS/AS region A and B. In the other two cases, one of which involved an inversion with one breakpoint in the PWS/AS region, all of the proximal chromosome 15 long arm DNA probes used in the in situ hybridization were present on both homologs. Clinical follow-up was not available on these samples, as in all cases the parents chose to terminate the pregnancies. These cases demonstrate the ability to prenatally diagnose chromosome 15 abnormalities associated with PWS/AS. In addition, they highlight the need for a better understanding of this region for accurate prenatal diagnosis.

Isochromosome 12p mosaicism (Pallister mosaic aneuploidy or Pallister-Killian syndrome): report of 11 cases.

We report on 11 cases of isochromosome 12p mosaicism (or Pallister mosaic aneuploidy syndrome) in which the isochromosome is usually absent in cultured lymphocytes but present in fibroblasts. The patients range in age from a 22-week-gestation fetus to a 45-year-old man. They have a distinct pattern of anomalies which enables one to make a diagnosis based on clinical manifestations alone. Craniofacial manifestations include "coarse" face with prominent forehead, sparsity of scalp hair, hypertelorism, epicanthal folds, flat bridge of nose, and highly arched palate. Affected newborn infants are profoundly hypotonic with sparsity of scalp hair especially bitemporally and a prominent forehead. Most have accessory nipples. Birthweight and growth parameters are usually normal; however, some newborn infants are unusually large. In infancy, the facial appearance becomes "coarse," hypotonia persists, and seizures may occur. As adults, growth may be normal, scalp hair is thicker and the mandible becomes prominent. Most have a generalized pigmentary dysplasia which may be evident with a Wood's lamp only. All cases have been sporadic and there is no consistent pattern of advanced parental age.

Weight outcomes among antidepressant users in nursing facilities.

OBJECTIVES: Depression is a common and treatable condition among nursing facility residents, with low body weight being a frequent concomitant concern. A common prescribing dictum is that older tricyclic antidepressants (TCAs) enhance appetite and may facilitate weight gain, while newer selective serotonin reuptake inhibitors (SSRIs) cause anorexia and resultant weight loss in older adults. Evidence is lacking on whether the small weight changes noted during short-term antidepressant efficacy trials translate into larger weight changes during prolonged treatment periods. Our main objective was to compare weight outcomes at 6 months among users of three different antidepressant groups with a control group of non-antidepressant users. A secondary objective was to determine whether antidepressant selection was associated with weight pattern before drug initiation, to capture possible prescribing bias that would affect study inferences. DESIGN: Retrospective cohort design using the Minimum Data Set--Plus (MDS+). SETTING: Kansas nursing facilities. PARTICIPANTS: 1,157 antidepressant users age 65 and older who started an antidepressant after admission and remained on the same single agent for at least 6 months, and 4,852 persons meeting the same inclusion/exclusion criteria but not receiving an antidepressant. MEASUREMENTS: Antidepressant use was identified by drug code data and divided into four groups for analysis: TCAs, SSRIs, others, and none. (Amitriptyline and trazodone were excluded because of frequent use for nondepression purposes.) Rates of clinically important loss and gain (assigned for a 10% change from baseline weight or presence of the significant loss or gain markers on the 6-month MDS assessment) and mean weight changes were compared across the four groups. Regression models were used to control for age, gender, baseline weight, confounding comorbidity, and functional variables related to eating. Previous weight patterns (loss, gain, neither, or unknown) before antidepressant initiation were compared across drug groups. RESULTS: Clinically important weight loss and gain occurred at 6 months in 14.8% and 14.4% of the sample, respectively. In unadjusted analyses, an increased likelihood of loss was found for users of SSRIs (Odds Ratio 1.57; CI 1.30, 1.90) and others (OR 1.89; CI 1.18, 3.03), compared with none. In logistic models accounting for potential confounding factors, however, SSRI use showed a modest association with gain (OR 1.31, CI 1.01, 1.70) and a trend toward a similarly modest association with loss (OR 1.28; CI 0.995, 1.64). TCA use was not associated with weight gain. When weight was examined as a continuous variable, all groups demonstrated a broad range of both loss and gain with mean-unadjusted weight changes < 3 pounds. Pairwise comparisons of adjusted differences in weight change at 6 months for SSRIs (mean loss of 1.6 pounds) and TCAs (mean gain of 0.4 pounds) were of marginal importance (P = .046) given the large sample size. No evidence was found for prescribing bias based on prior weight pattern. CONCLUSIONS: TCAs do not facilitate weight gain more than other antidepressant groups and SSRIs are not associated disproportionately with weight loss when other important clinical variables are accounted for. Small but statistically significant differences in mean weight changes between groups are largely a reflection of large sample size rather than clinically important differences. Clinicians may wish to reconsider the widely held notions that TCAs facilitate weight gain and that SSRIs place depressed older nursing facility residents at disproportionate risk for weight loss.

Radical hysterectomy: influence of recent conization on morbidity and complications.

From 1956 through 1975, 610 radical hysterectomies with pelvic lymphadenectomy were performed at the Mayo Clinic. Eighty-eight of these operations were done after conization of the cervix: 7, within 7 days; 74, between 8 and 28 days; and 7, on or after the 29th day. Operative febrile morbidity was not increased in the patients who had conization, and they also required fewer blood transfusions than the patients without previous conization. Incidences of all postoperative complications except pulmonary embolism were lower in the patients with cone biopsy than in those without. Of the 88 patients, 77% received antibiotics prophylactically during the operative period. There appeared to be no serious contraindications to performing radical hysterectomy and pelvic lymphadenectomy at any interval after diagnostic conization of the cervix.

Wertheim hysterectomy: a reappraisal.

A total of 610 radical hysterectomies with bilateral pelvic lymphadenectomy were performed at the Mayo Clinic in the 20-year period from 1956 through 1975. This operative procedure was the primary therapy in 74% of the patients, the others having had previous pelvic irradiation. Operative morbidity, postoperative complications, lymph node involvement, and overall survival were analyzed.

Management of the pelvic floor after pelvic exenteration.

At the Mayo Clinic, 198 exenterative operations were performed from 1950 through 1971. Although the 5-year survival rate of all patients was 33%, bowel obstruction occurred in 11.6% of patients and intestinal fistula formation in 12.6%. The majority of patients with these complications had had previous pelvic irradiation. The difficulty in dealing with the large raw area in the pelvis is discussed with a review of the various methods that have been tried to date to reperitonealize the pelvis and thereby, it is hoped, prevent adhesions or fistula formation.

Treatment of placental site trophoblastic tumor with hysterotomy and uterine reconstruction.

BACKGROUND: Placental site trophoblastic tumor is an unusual variant of gestational trophoblastic neoplasia that is usually confined to the uterus, although 10% of patients have metastases. Because this tumor occurs in women of reproductive age, preservation of fertility may be relevant. Therefore, local excision of placental site trophoblastic tumor by hysterotomy may have a place in management. CASE: A 25-year-old woman, gravida 1, para 1, presented with irregular bleeding. Uterine curettage revealed intermediate trophoblasts that on immunostaining were positive for hCG and human placental lactogen, consistent with placental site trophoblastic tumor. Endovaginal ultrasonography and magnetic resonance imaging demonstrated tumor localized to the anterior fundal myometrium. The patient underwent local excision of the tumor by hysterotomy followed by uterine reconstruction. Pathologic examination confirmed that the surgical margins were free of tumor. The patient has had no recurrence. Two subsequent pregnancies resulted in two spontaneous abortions. A third pregnancy was carried to term. The patient was delivered by cesarean because of the hysterotomy. The hysterotomy scar was intact at cesarean. CONCLUSION: Hysterectomy has been recommended by most authors for treatment for placental site trophoblastic tumor. In some patients with localized placental site trophoblastic tumor who desire preservation of fertility, more conservative surgical therapy may be considered.