Sub-ppm Nanomechanical Absorption Spectroscopy of Silicon Nitride.

Material absorption is a key limitation in nanophotonic systems; however, its characterization is often obscured by scattering and diffraction. Here we show that nanomechanical frequency spectroscopy can be used to characterize material absorption at the parts per million level and use it to characterize the extinction coefficient κ of stoichiometric silicon nitride (Si3N4). Specifically, we track the frequency shift of a high-Q Si3N4 trampoline in response to laser photothermal heating and infer κ from a model including stress relaxation and both conductive and radiative heat transfer. A key insight is the presence of two thermalization time scales: rapid radiative cooling of the Si3N4 film and slow parasitic heating of the Si chip. We infer κ ∼ 0.1-1 ppm for Si3N4 in the 532-1550 nm wavelength range, matching bounds set by waveguide resonators. Our approach is applicable to diverse photonic materials and may offer new insights into their potential.

Association between potentially inappropriate medications prescription and health-related quality of life among US older adults.

BACKGROUND: Potentially inappropriate medications (PIMs) are associated with worse health outcomes among older adults. Our objective was to examine the association between PIM prescription and health-related quality of life (HRQoL) among older adults in the United States using nationally representative data. METHODS: This was a retrospective study utilizing 2011-2015 Medical Expenditure Panel Survey (MEPS) data. Community dwelling US adults aged 65 years or older were included. A qualified definition operationalized from the 2019 American Geriatrics Society Beers Criteria® was used to define exposure to PIMs during the study period. The Physical Component Summary (PCS) and Mental Component Summary (MCS) of the Medical Outcomes Study 12-Item Short Form Health Survey (SF-12) were used to measure HRQoL. Survey-weighted linear regression models were constructed to investigate the association between PIM exposure and participants' PCS and MCS scores. Analyses were stratified across three age cohorts (65-74, 75-85, and ≥85 years). RESULTS: Unadjusted analysis showed poorer scores in the PIM exposed group for both PCS and MCS (all p < 0.001). PIM exposure was associated with poorer PCS scores across all age groups with those aged 65-74 years (adjusted regression coefficient = -1.60 [95% CI = -2.27, -0.93; p < 0.001]), those 75-84 years (adjusted regression coefficient: -1.49 [95% CI = -2.45, -0.53; p = 0.003]), and those 85 years and older (adjusted regression coefficient = -1.65 [95% CI = -3.03, -0.27; p = 0.02]). PIM exposure was also associated with poorer MCS scores in participants aged 65-74 years (adjusted regression coefficient = -0.69 [95% CI = -1.16, -0.22; p = 0.004]) and 85 years and older (adjusted regression coefficient = -2.01 [95% CI = -3.25, -0.78; p = 0.002]). CONCLUSIONS: Our results suggest that patients' exposure to PIMs is associated with poorer HRQoL. Further work is needed to assess whether interventions to deprescribe PIMs may help to improve patients' HRQoL.

Impact of COVID-19 on mortality in coastal Kenya: a longitudinal open cohort study.

The mortality impact of COVID-19 in Africa remains controversial because most countries lack vital registration. We analysed excess mortality in Kilifi Health and Demographic Surveillance System, Kenya, using 9 years of baseline data. SARS-CoV-2 seroprevalence studies suggest most adults here were infected before May 2022. During 5 waves of COVID-19 (April 2020-May 2022) an overall excess mortality of 4.8% (95% PI 1.2%, 9.4%) concealed a significant excess (11.6%, 95% PI 5.9%, 18.9%) among older adults ( ≥ 65 years) and a deficit among children aged 1-14 years (-7.7%, 95% PI -20.9%, 6.9%). The excess mortality rate for January 2020-December 2021, age-standardised to the Kenyan population, was 27.4/100,000 person-years (95% CI 23.2-31.6). In Coastal Kenya, excess mortality during the pandemic was substantially lower than in most high-income countries but the significant excess mortality in older adults emphasizes the value of achieving high vaccine coverage in this risk group.

HIV testing in jails: Comparing strategies to maximize engagement in HIV treatment and prevention.

Despite 15,000 people enter US jails yearly with undiagnosed HIV infection, routine HIV testing is not standard. Maximizing the yield and speed of HIV testing in short-term detention facilities could promote rapid entry or re-entry of people living with HIV (PLWH) into care. The goal of this study was to evaluate the impact of third generation, rapid point-of-care (rPOC) vs. fourth generation, laboratory-based antigen/antibody (LBAg/Ab) testing on the HIV care cascade in a large urban jail during a planned transition. We used aggregate historical data to compare rPOC testing and LBAg/Ab testing in the D.C. Department of Corrections. We examined two time periods, January to August 2019 when rPOC testing was performed, and October 2019 to January 2020 after LBAg/Ab testing began. We calculated monthly rates of HIV tests performed, HIV test results received, HIV test results received among those tested, antiretroviral therapy (ART) initiation, and proportion of PLWH receiving discharge planning prior to release. We then conducted an interrupted time series analysis to assess the differences between testing periods. There were 14,237 entrants during the first time period and 7,569 entrants during the second. Transitioning from rPOC to LBAg/Ab testing increased the rate of test uptake by 38.5% (95% CI: 14.0, 68.3), decreased the rate of test results received among those tested by 13.1% (95% CI: -14.0, -12.1), and increased the combined rate of HIV tests performed and results received by 20.4% (95% CI: 1.5, 42.8). Although the rate of HIV testing was greater under LBAg/Ab, PLWH received results immediately through rPOC testing, which is critically important in short-stay enviroments. Increasing rPOC uptake would increase its value and combined testing may maximize the detection of HIV and receipt of results among persons passing through jails.

Towards cavity-free ground-state cooling of an acoustic-frequency silicon nitride membrane.

We demonstrate feedback cooling of a millimeter-scale, 40 kHz SiN membrane from room temperature to 5 mK (3000 phonons) using a Michelson interferometer, and discuss the challenges to ground-state cooling without an optical cavity. This advance appears within reach of current membrane technology, positioning it as a compelling alternative to levitated systems for quantum sensing and fundamental weak force measurements.

Patient Safety Friendly Hospital Initiative: from evidence to action in seven developing country hospitals.

QUALITY PROBLEM: Recent evidence in the level of patient safety from hospitals in six developing countries in the Eastern Mediterranean Region has demonstrated the high prevalence of adverse events, the excessive rate of death and permanent disability and their high preventability. The Patient Safety Friendly Hospital Initiative (PSFHI) has been launched to respond to these challenges. INITIAL ASSESSMENT: The principal approach of the PSFHI has been to develop an assessment manual that has 140 patient safety standards across five domains--leadership and management, patients and public involvement, safe evidence-based clinical practices, safe environment and lifelong learning. CHOICE OF SOLUTION AND IMPLEMENTATION: Ministries of health of seven countries--Egypt, Jordan, Morocco, Pakistan, Sudan, Tunisia and Yemen were asked to nominate one hospital for assessment and then follow-up with an improvement plan. EVALUATION: The standards are divided into critical (20), core (90) and developmental (30). The range of critical standards, the compulsory standards with which a hospital has to comply, achieved by participating hospitals was 8-78%. Overall, in the domain of leadership and management the highest compliance was 47%, for patients and public involvement 25%, for safe evidence-based clinical practice 53%, for safe environment 64% and for lifelong learning 27%. LESSONS LEARNED: This is the first systematic multi-country initiative in the Eastern Mediterranean Region, which provides compelling evidence that assessment of patient safety standards is feasible and applicable in resource-poor settings and there are significant opportunities for improving the level of patient safety in these hospitals.

Efficacy of double gloving technique in major and minor oral surgical procedures: A prospective study.

BACKGROUND: A prospective analysis was carried out over a 1-year period to assess gloves used during 100 major and 100 minor oral surgical procedures to test for efficacy of double gloving in oral surgical procedures. PURPOSE: The purpose of this study was to assess the efficacy of double gloving technique in preventing cross infection in both major and minor oral surgical procedures. MATERIALS AND METHODS: Gloves used during 100 major and 100 minor oral surgical procedures were analyzed to check for glove perforations and skin punctures. 100 sterile gloves were tested as control. STATISTICAL ANALYSIS USED: Chi-square test was used to determine whether there was any difference between the expected and observed values in various categories. RESULTS: A higher number of glove perforations was seen in minor oral surgical procedures compared with major surgeries, dominant hand compared with the nondominant, outer gloves compared with the inner, in procedures which took a longer duration of time to complete, in procedures involving wiring and in the index finger followed by the thumb and the palm. CONCLUSION: Double gloving technique using sterile gloves can be used as an effective means of infection control for all major and minor surgical procedures, especially high-risk procedures involving patients who maybe suffering from or carriers of blood-borne infections.

A novel sortase, SrtC2, from Streptococcus pyogenes anchors a surface protein containing a QVPTGV motif to the cell wall.

The important human pathogen Streptococcus pyogenes (group A streptococcus GAS), requires several surface proteins to interact with its human host. Many of these are covalently linked by a sortase enzyme to the cell wall via a C-terminal LPXTG motif. This motif is followed by a hydrophobic region and charged C terminus, which are thought to retard the protein in the cell membrane to facilitate recognition by the membrane-localized sortase. Previously, we identified two sortase enzymes in GAS. SrtA is found in all GAS strains and anchors most proteins containing LPXTG, while SrtB is present only in some strains and anchors a subset of LPXTG-containing proteins. We now report the presence of a third sortase in most strains of GAS, SrtC. We show that SrtC mediates attachment of a protein with a QVPTGV motif preceding a hydrophobic region and charged tail. We also demonstrate that the QVPTGV sequence is a substrate for anchoring of this protein by SrtC. Furthermore, replacing this motif with LPSTGE, found in the SrtA-anchored M protein of GAS, leads to SrtA-dependent secretion of the protein but does not lead to its anchoring by SrtA. We conclude that srtC encodes a novel sortase that anchors a protein containing a QVPTGV motif to the surface of GAS.

Characterization of indigenous fat-tailed and fat-rumped hair sheep in Kenya: diversity in blood proteins.

This paper reports the variation in five blood proteins from five populations of sheep found in Kenya. Blood samples were collected from a total of 309 adult sheep of both sexes in Kwale, Makueni and Kakamega districts for the fat-tailed sheep and in Isiolo district for the fat-rumped hair sheep. Fine-wooled Merino sheep were used in this study as the reference population. Transferrin, esterase-A and esterase-C were polymorphic in all the populations investigated, while albumin was monomorphic for the S allele in the fat-tailed sheep and haemoglobin was fixed for the B allele in the Kwale, Makueni and Isiolo populations. Phylogenies derived from the pairwise genetic distance estimates showed a clear separation between the indigenous sheep populations and the exotic Merino. However, the topology of the former showed rather poor consistency with their morphological classification based on the localization of their fat deposits, namely fat-tailed or fat-rumped hair sheep.

Centric fusion polymorphisms in waterbuck (Kobus ellipsiprymnus).

Twenty-six captive individuals of the ellipsiprymnus subspecies group of Kobus ellipsiprymnus were found to have chromosomal complements of 2n = 50-52 (FN = 61-62), and 26 of the defassa subspecies group, including three specimens from Lake Nakuru National Park, Kenya, had complements of 2n = 53-54 (FN = 62). G-banded karyotypes that were numbered according to the standard karyotype of Bos taurus revealed that variation in diploid number was the result of polymorphism for two independent centric (Robertsonian) fusions. The ellipsiprymnus group was polymorphic for a 7;11 centric fusion. Both elements of chromosome pairs 7 and 11 were fused in fusion homozygotes (2n = 50); in fusion heterozygotes (2n = 51), only one element of each pair was fused. The 7;11 fusion was lacking in specimens with 2n = 52. The defassa group was polymorphic for a 6;18 centric fusion; individuals were either heterozygous for the fusion (2n = 53) or lacking it (2n = 54). There were no defassa group individuals that were homozygous for the 6;18 fusion (2n = 52), but this may be a sampling artifact. The 6;18 fusion was fixed in the ellipsiprymnus group, whereas the 7;11 fusion was absent in the defassa group. In G- and C-banded karyotypes, all autosomal arms and the X chromosomes of the two subspecies groups appeared to be completely homologous. However, the Y chromosome was acrocentric in the ellipsiprymnus group and submetacentric in the defassa group, possibly the result of a pericentric inversion. Fixed chromosomal differences between the two subspecies groups reflect a period of supposed geographic isolation during which time they diverged genetically and phenotypically, and the centric fusion polymorphisms raise the possibility of reduced fertility in hybrids. These data, in conjunction with phenotypic and mitochondrial DNA data, suggest to us that populations of the ellipsiprymnus and defassa groups should be managed separately.

Corticosteroid use and abuse by medical practitioners for arthritis and related disorders in Pakistan.

A total of 256 consecutive patients attending our out-patient clinic in Islamabad, Pakistan, with complaints of pain in or around the joints were evaluated for use of corticosteroids prescribed by medical practitioners they had seen earlier. The appropriateness of such prescriptions and their consequent effects were assessed. Of the 256 patients, 110 (i.e. 42.5%) were identified as steroid users; some of them were suffering from conditions known to be unresponsive to this form of therapy. One hundred and one of the 256 patients had rheumatoid arthritis and 67% of these had been using steroids, mostly in an irrational manner. The general practitioners and consultants (all non-rheumatologists) were responsible for the majority of steroid prescriptions. Steroid side-effects were observed in 42/110 (38.2%) cases. This prevalent practice in Pakistan is a reflection of the state of affairs in developing countries, and indicates a need for improvement and better regulation of health care in such countries.

mtDNA sequence diversity in Africa.

mtDNA sequences were determined from 241 individuals from nine ethnic groups in Africa. When they were compared with published data from other groups, it was found that the !Kung, Mbuti, and Biaka show on the order of 10 times more sequence differences between the three groups, as well as between those and the other groups (the Fulbe, Hausa, Tuareg, Songhai, Kanuri, Yoruba, Mandenka, Somali, Tukana, and Kikuyu), than these other groups do between one other. Furthermore, the pairwise sequence distributions, patterns of coalescence events, and numbers of variable positions relative to the mean sequence difference indicate that the former three groups have been of constant size over time, whereas the latter have expanded in size. We suggest that this reflects subsistence patterns in that the populations that have expanded in size are food producers whereas those that have not are hunters and gatherers.

Extreme genetic differences among populations of Gazella granti, Grant's gazelle in Kenya.

Mitochondrial DNA (mtDNA) control region sequences from six Kenyan Grant's gazelle (Gazella granti) populations were highly divergent among locations. Neighbouring populations not separated by geographical or vegetational barriers exhibited and nucleotide sequence divergence about 14 per cent. A similar level of divergence separates Grant's gazelles from a closely related species, the Soemmering's gazelle (G. soemmeringii). Nuclear microsatellite repeat number variation at two loci also indicated substantial population genetic differentiation. Despite high levels of sequence divergence populations of Grant's gazelles were more closely related to each other than to Soemmering's and Thompson's gazelles (G. thomsoni) as measured by nucleotide sequence divergence at the mtDNA protein coding cytochrome b gene and the nuclear alpha-lactalbumin gene. This pattern of extensive differentiation is hypothesized to have resulted from recently established contacts between formerly allopatric populations.

Characterization of a native and recombinant Schistosoma haematobium serine protease inhibitor gene product.

Immunologic screening of a Schistosoma haematobium cDNA library with species-specific human antisera identified a clone whose predicted amino acid sequence encodes a member of the serine protease inhibitor (serpin) gene family. This cDNA consists of 1397 bp with a single open reading frame that can encode a 409-amino acid protein of 46,261 Da. The native antigen is a 54-58-kDa glycoprotein and is located on the surface of adult worms. Sequence comparison with other serpins predicts the amino acid Phe at the putative reactive center of the protein. Phenylalanine is also found at the corresponding site of a vaccinia serpin that may contribute to the hemorrhagic phenotype of some strains of cowpox virus. Though the human parasites S. haematobium and Schistosoma mansoni demonstrate a close antigenic relationship, the S. haematobium serpin gene product demonstrates marked species-specific immunogenicity. By Northern blot hybridization, however, both species express a 1700-nucleotide mRNA that hybridizes with the S. haematobium serpin cDNA. The intensity of cross hybridization for the S. mansoni mRNA is 10-fold lower than that for S. haematobium. Southern blots of genomic DNA and gene titration experiments indicate that the S. haematobium gene is present in approximately 4-5 copies per haploid genome.

Effects of cooling and rewarming on the meiotic spindle and chromosomes of in vitro-matured bovine oocytes.

The purpose of this study was to evaluate effects of cooling and rewarming on the meiotic spindle apparatus of bovine oocytes. In experiment 1, in vitro-matured bovine oocytes were either maintained at 39 degrees C or cooled abruptly to 4 degrees C or approximately 25 degrees C. Immunohistochemical and DNA staining for visualization of microtubules and chromosomes, respectively, revealed an anastral, barrel-shaped spindle in bovine oocytes. Exposure to 4 degrees C for 10-20 min caused complete disappearance of the spindle. Some chromosome dispersion occurred after 60 min at 4 degrees C. After exposure to approximately 25 degrees C for 30 min, 90% of oocytes appeared abnormal, having either an abnormal spindle or no spindle. In experiment 2, oocytes cooled to either approximately 25 degrees C or 4 degrees C for 30 min were rewarmed directly or in steps for 15 or 60 min. Spindles did not return to normal in most oocytes regardless of cooling temperature or rewarming scheme. Step-wise rewarming was no more beneficial than direct rewarming. More of the oocytes rewarmed directly contained dispersed chromosomes as time at 39 degrees C increased.

Inhibition of protein synthesis results in super-induction of procyclin (PARP) RNA levels.

Procyclin is an abundant surface antigen found exclusively on the procyclic forms of African trypanosomes. We are interested in the induction of procyclin gene expression during differentiation from bloodstream forms. We find that increased levels of procyclin RNA are evident as early as 15 min after triggering differentiation. The increase in procyclin RNA levels requires the temperature shift from 37 degrees C to 27 degrees C and is aided by addition of the tricarboxylic acid cycle intermediate cis-aconitate. Maximal induction is observed with a combination of three triggers of differentiation: citrate, cis-aconitate and the temperature shift. Protein synthesis does not appear to be required for induction of procyclin RNA during differentiation. In fact, addition of protein synthesis inhibitors results in super-induction of procyclin RNA levels, even under conditions where no induction is normally observed (i.e., at 37 degrees C in the absence of citrate and cis-aconitate). This super-induction was observed with four different protein synthesis inhibitors that affect different stages of translation. Thus, the accumulation of procyclin transcripts may be under the control of a negative regulator whose effective levels are reduced during differentiation from bloodstream to procyclic forms.

Identification of two integral glycosomal membrane proteins in Trypanosoma brucei.

Glycosomal membranes of bloodstream form Trypanosoma brucei were purified to apparent homogeneity by sodium carbonate treatment and found to contain two major integral membrane proteins of 26 kDa (band 10) and 24 kDa (band 11). The procyclic-form glycosomal membranes isolated by the same procedure also resulted in a homogeneous preparation, but each piece of membrane thus purified was associated with an electron-dense granule. Procyclic membranes also contained primarily bands 10 and 11. These two proteins were selectively reduced by protease treatment of intact glycosomes, suggesting surface exposed domain(s) of the two proteins accessible to proteolytic digestion. They and band 8 protein also vanished in glycosomal lysates by apparent proteolysis, implying the presence of a specific protease which degrades the integral membrane proteins upon the loss of membrane integrity. The two proteins, hydrophobic in nature and apparently unglycosylated, have no known biological functions, but their possible involvement in translocating precursor proteins from the cytoplasm into the glycosome of T. brucei is postulated.