Dementia with Lewy bodies (DLB) was considered to be an uncommon cause of dementia until improved neuropathological staining methods for ubiquitin were developed in the late 1980's. Subsequent ...recognition that 10-15% of dementia cases in older people were associated with Lewy body pathology led to the publication in 1996 of Consensus clinical and pathological diagnostic criteria for the disorder. These have greatly raised global awareness of DLB and helped to generate a body of knowledge which informs modern clinical management of this pharmacologically sensitive group of patients. They have also enabled important issues surrounding the relationships of DLB with Alzheimer's disease and Parkinson's disease to be addressed and partially resolved. A recent re-evaluation of the Consensus criteria has confirmed many aspects of the original recommendations, supplementing these with suggestions for improved pathological characterisation, clinical detection and management. Virtu-ally unrecognised 20 years ago, DLB could within this decade be one of the best characterised and potentially treatable neurodegenerative disorders of late life.
The radiation belts and plasma in the Earth’s magnetosphere pose hazards to satellite systems which restrict design and orbit options with a resultant impact on mission performance and cost. For ...decades the standard space environment specification used for spacecraft design has been provided by the NASA AE8 and AP8 trapped radiation belt models. There are well-known limitations on their performance, however, and the need for a new trapped radiation and plasma model has been recognized by the engineering community for some time. To address this challenge a new set of models, denoted AE9/AP9/SPM, for energetic electrons, energetic protons and space plasma has been developed. The new models offer significant improvements including more detailed spatial resolution and the quantification of uncertainty due to both space weather and instrument errors. Fundamental to the model design, construction and operation are a number of new data sets and a novel statistical approach which captures first order temporal and spatial correlations allowing for the Monte-Carlo estimation of flux thresholds for user-specified percentile levels (e.g., 50th and 95th) over the course of the mission. An overview of the model architecture, data reduction methods, statistics algorithms, user application and initial validation is presented in this paper.
With broadening indications, more options for hematopoietic cell transplantation (HCT) and improvement in survival, the number of long-term HCT survivors is expected to increase steadily. Infertility ...is a frequent problem that long-term HCT survivors and their partners face and it can negatively impact on the quality of life. The most optimal time to address fertility issues is before the onset of therapy for the underlying disease; however, fertility preservation should also be addressed before HCT in all children and patients of reproductive age, with referral to a reproductive specialist for patients interested in fertility preservation. In vitro fertilization (IVF) and embryo cryopreservation, oocyte cryopreservation and ovarian tissue banking are acceptable methods for fertility preservation in adult women/pubertal females. Sperm banking is the preferred method for adult men/pubertal males. Frequent barriers to fertility preservation in HCT recipients may include the perception of lack of time to preserve fertility given an urgency to move ahead with transplant, lack of patient-physician discussion because of several factors (for example, time constraints, lack of knowledge), inadequate access to reproductive specialists, and costs and lack of insurance coverage for fertility preservation. There is a need to raise awareness in the medical community about fertility preservation in HCT recipients.
Germline mutations of the BRCA1 gene account for approximately 5% of breast and ovarian cancer cases, and lower than normal BRCA1 expression or function may be an important contributing factor in ...sporadic cancers. The major role of BRCA1 is to respond to DNA damage by participating in cellular pathways for DNA repair, mRNA transcription, cell cycle regulation, and protein ubiquitination. Because most chemotherapeutic agents function by directly or indirectly damaging DNA, the role of BRCA1 as a regulator of chemotherapy-induced DNA damage has been the subject of an increasing number of investigations. We review published preclinical and clinical evidence that the level of BRCA1 function in an individual patient's tumor can guide the choice of chemotherapeutic agents for breast and ovarian cancer. We conclude that a loss of BRCA1 function is associated with sensitivity to DNA-damaging chemotherapy and may also be associated with resistance to spindle poisons. We recommend that prospective clinical studies investigating the role of BRCA1 in the response to chemotherapy be conducted.
Polyethylene (PE) multiwalled carbon nanotubes (MWCNTs) with weight fractions ranging from 0.1 to 10wt% were prepared by melt blending using a mini-twin screw extruder. The morphology and degree of ...dispersion of the MWCNTs in the PE matrix at different length scales was investigated using scanning electron microscopy (SEM), transmission electron microscopy (TEM), atomic force microscopy (AFM) and wide-angle X-ray diffraction (WAXD). Both individual and agglomerations of MWCNTs were evident. An up-shift of 17cm−1 for the G band and the evolution of a shoulder to this peak were obtained in the Raman spectra of the nanocomposites, probably due to compressive forces exerted on the MWCNTs by PE chains and indicating intercalation of PE into the MWCNT bundles. The electrical conductivity and linear viscoelastic behaviour of these nanocomposites were investigated. A percolation threshold of about 7.5wt% was obtained and the electrical conductivity of PE was increased significantly, by 16 orders of magnitude, from 10−20 to 10−4S/cm. The storage modulus (G′) versus frequency curves approached a plateau above the percolation threshold with the formation of an interconnected nanotube structure, indicative of ‘pseudo-solid-like’ behaviour. The ultimate tensile strength and elongation at break of the nanocomposites decreased with addition of MWCNTs. The diminution of mechanical properties of the nanocomposites, though concomitant with a significant increase in electrical conductivity, implies the mechanism for mechanical reinforcement for PE/MWCNT composites is filler-matrix interfacial interactions and not filler percolation. The temperature of crystallisation (Tc) and fraction of PE that was crystalline (Fc) were modified by incorporating MWCNTs. The thermal decomposition temperature of PE was enhanced by 20K on addition of 10wt% MWCNT.
Quality of life (QOL) is increasingly recognized as an important clinical outcome of hematopoietic cell transplantation (HCT), but patient education is often overlooked. The aim of the current ...qualitative study was to examine education regarding post-HCT QOL from the patient's perspective. Allogeneic HCT recipients participated in one of four focus groups. Participants were asked to recall what they had been told about post-HCT QOL as they were preparing for transplant, how their QOL differed from what they expected and how to educate future patients about post-HCT QOL. Verbatim transcripts were coded for both a priori and emergent themes using content analysis. A total of 24 patients participated (54% female, mean age 51, range 23-73 years). Participants frequently expressed the desire for additional education regarding post-HCT QOL, particularly late complications. They noted that late complications were often unexpected, had a profound impact on their QOL and threatened their ongoing sense of recovery. They emphasized that the timing, content and format of education regarding QOL should be flexible to meet their diverse needs. Findings from the current study draw attention to the importance of patient education regarding post-HCT QOL as well as additional QOL research designed with patient education in mind.
What structural (logistical) and psychological challenges do patients who cryopreserve oocytes or embryos for medical reasons face, including possible barriers to using their frozen materials?
The ...majority of women who underwent oocyte or embryo cryopreservation for medical reasons reported a desire to use their frozen oocytes or embryos but had been impeded by ongoing medical issues, the need for a gestational carrier, or the lack of a partner.
Current data suggest that many women who have frozen oocytes or embryos for medical indications are concerned about the prospect of infertility and have unique emotional and financial needs that differ from patients with infertility. Further, most patients have not returned to use their cryopreserved materials.
This is a qualitative interview study of 42 people who cryopreserved between January 2012 and December 2021. Interviews were conducted between March 2021 and March 2022.
All participants were cisgender women who had undergone oocyte or embryo cryopreservation for medical indications at an academic fertility center. Participants were invited to interview by email if they were younger than 40 years old when their oocytes or embryos were cryopreserved. Interviews were conducted over the internet and transcribed verbatim. Data were analyzed using thematic analysis with the constant comparison method.
Saturation was reached at 42 interviews. The median age of participants was 35 years old (range 28-43) at interview and 31 years old (range 25-39) at cryopreservation. Of the 42 women, 30 had a cancer diagnosis, while 7 had non-cancer chronic medical conditions, and 5 had hereditary cancer susceptibility syndromes. There were 12 women who banked embryos and 30 who banked oocytes. The majority of women indicated a desire to use their cryopreserved materials, but many were unsure about how or when. Four had already used their frozen oocytes or embryos, while another four had conceived without assisted reproduction. The cryopreservation experience was described by the majority as highly emotionally challenging because they felt out of place among couples receiving infertility treatment and, for cancer patients, overwhelmed by the complex decisions to be made in a short time period. Common reported barriers to using frozen materials included ongoing medical issues preventing pregnancy, the need for a gestational carrier, the lack of a partner, and the desire for unassisted conception. Some were glad to have frozen oocytes or embryos to allow more time to meet a partner or if they were considering becoming single parents.
The majority of participants had their oocytes or embryos frozen at a single, urban, academic fertility center, which may limit generalizability. We also could not calculate a response rate because the snowball technique was used to identify additional participants, so did not know the total number of people invited to participate. Like other interview studies, our study may be subject to response bias because those who agreed to participate may have particularly positive or negative views about their experiences. Furthermore, the mean follow-up time since freezing was relatively short (3.3 years, median 2.7 years), which may not have been enough time for some patients to use their frozen materials.
Learning about the experiences of patients undergoing medically indicated oocyte and embryo cryopreservation can help clinicians better counsel these patients regarding decisions and hurdles they may encounter. We found that most patients had not returned to use their frozen materials because of ongoing medical issues, the need for a gestational carrier, lack of a partner, or the desire to attempt unassisted reproduction.
This study did not receive any funding. The authors of this study have no conflicts of interest to declare.
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In the last two decades, mortality from primary liver cancer has increased in the UK. We aimed to determine whether the incidence trends for these cancers were similar and in particular if the ...increasing occurrence of cholangiocarcinoma has continued. We calculated directly age-standardised incidence rates (using the European standard population) by subsite and histological type for all cancers of the liver, gallbladder and biliary tract in England and Wales from 1971 to 2001, using cancer registry data. The incidence of cancers of the liver, gallbladder and biliary tract increased, with the greatest rise, around 12-fold, in intrahepatic bile duct cancers. The rate of liver cell cancer increased by around 45% in males, but by <10% in females. There were marked reductions in the incidence of gallbladder and extrahepatic bile duct cancer. Cholangiocarcinoma increased around 16-fold and became the most common type of primary liver cancer in females, while hepatocellular carcinoma remained the commonest type in males. The age-specific incidence rates showed that intrahepatic bile duct cancer continued to increase throughout the 1990s in those aged 75 and over, while liver cell cancer decreased in the older age groups. In conclusion, there were increases in the incidence of primary liver cancer, which have been particularly dramatic for intrahepatic bile duct cancer, over the last three decades of the 20th century in England and Wales. There has been a halving in the incidence of gallbladder cancer and a reduction of a third in extrahepatic bile duct cancer.
Major depressive disorder (MDD) is associated with an increased risk of brain atrophy, aging-related diseases, and mortality. We examined potential advanced brain aging in adult MDD patients, and ...whether this process is associated with clinical characteristics in a large multicenter international dataset. We performed a mega-analysis by pooling brain measures derived from T1-weighted MRI scans from 19 samples worldwide. Healthy brain aging was estimated by predicting chronological age (18-75 years) from 7 subcortical volumes, 34 cortical thickness and 34 surface area, lateral ventricles and total intracranial volume measures separately in 952 male and 1236 female controls from the ENIGMA MDD working group. The learned model coefficients were applied to 927 male controls and 986 depressed males, and 1199 female controls and 1689 depressed females to obtain independent unbiased brain-based age predictions. The difference between predicted "brain age" and chronological age was calculated to indicate brain-predicted age difference (brain-PAD). On average, MDD patients showed a higher brain-PAD of +1.08 (SE 0.22) years (Cohen's d = 0.14, 95% CI: 0.08-0.20) compared with controls. However, this difference did not seem to be driven by specific clinical characteristics (recurrent status, remission status, antidepressant medication use, age of onset, or symptom severity). This highly powered collaborative effort showed subtle patterns of age-related structural brain abnormalities in MDD. Substantial within-group variance and overlap between groups were observed. Longitudinal studies of MDD and somatic health outcomes are needed to further assess the clinical value of these brain-PAD estimates.
Enterobacter sakazakii represents a significant risk to the health of neonates. This bacterium is an emerging opportunistic pathogen that is associated with rare but life-threatening cases of ...meningitis, necrotizing enterocolitis, and sepsis in premature and full-term infants. Infants aged <28 days are considered to be most at risk. Feeding with powdered infant formula (PIF) has been epidemiologically implicated in several clinical cases. Infants should be exclusively breast-fed for the first 6 months of life, and those who are not should be provided with a suitable breast-milk substitute. PIF is not a sterile product; to reduce the risk of infection, the reconstitution of powdered formula should be undertaken by caregivers using good hygienic measures and in accordance with the product manufacturer's food safety guidelines.
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