A Qualitative Analysis of Gabapentin Misuse and Diversion Among People Who Use Drugs in Appalachian Kentucky

Gabapentin, an anticonvulsant and analgesic for postherpetic neuralgia, has been thought to have no abuse potential despite numerous published reports to the contrary. Gabapentin has been linked with impaired driving and opioid use, highlighting the need to more fully understand its risk profile. Thirty-three individuals reporting recent nonmedical use of gabapentin were recruited from two ongoing longitudinal studies of drug users in Appalachian Kentucky to participate in focus groups. Four sessions were held (two in the community and two in jail settings), during which participants responded to questions regarding their personal experiences with gabapentin misuse. Focus group participants were similar to other gabapentin users in the larger cohort studies with respect to demographics and drug use behaviors. Overall, the sample reported having initiated gabapentin more than 10 years earlier after having it prescribed for a legitimate, though generally off-label, medical indication (e.g., pain, anxiety, opioid detoxification). Participants reported use of gabapentin in combination with buprenorphine, other opioids, cocaine, and caffeine to produce sought-after central nervous system effects (e.g., muscle relaxation, pain reduction, sleep induction, feeling drunk, and feeling “high”). Focus group responses highlighted the low cost of gabapentin for the purpose of getting high and noted increasing popularity in the community, particularly over the last 2 years. Gabapentin was a prominent drug of abuse in two cohorts of the primarily opioid-using individuals. Providers should be aware of gabapentin’s abuse potential, and a reexamination of the need for scheduling is warranted

Clinical Outcomes for BRCA Pathogenic Variant Carriers With Breast Cancer Undergoing Breast Conservation

IMPORTANCE: Although most women with BRCA-associated breast cancer choose bilateral mastectomy, current guidelines support breast-conserving therapy as an option. As the indications for genetic testing expand and targeted therapies emerge, understanding the outcomes of breast-conserving therapy in the population of patients choosing breast conservation is important. OBJECTIVE: To describe the clinical outcomes of women with BRCA-associated breast cancer who were treated with breast-conserving therapy, including the risks of ipsilateral and contralateral cancer events and bilateral mastectomy-free survival. DESIGN, SETTING, AND PARTICIPANTS: This cohort study conducted at a single-institution academic national comprehensive cancer center included 172 women identified from a prospectively maintained database who had pathogenic BRCA1/2 variants and were treated with breast-conserving therapy from January 1, 1977, to December 31, 2021. MAIN OUTCOMES AND MEASURES: Clinical and pathologic characteristics for patients with BRCA1 and BRCA2 were compared, and estimates of overall survival, bilateral mastectomy-free survival, distant disease-free survival, risk of ipsilateral breast cancer, and risk of contralateral cancer were computed. RESULTS: The cohort included 172 women (mean [SD] age, 47.1 [11.7] years), with 42 (24.4%) receiving a diagnosis of breast cancer prior to 40 years of age. Compared with BRCA2 variant carriers (80 [46.5%]), women with BRCA1 variants (92 [53.5%]) were younger at breast cancer diagnosis and tended to have more advanced tumors, which were more likely to be hormone receptor negative and higher grade. At a median follow-up of 11.8 years (IQR, 5.7-18.2 years), estimates of 10-year survival and risk were: overall survival, 88.5% (95% CI, 83.1%-94.2%); bilateral mastectomy-free survival, 70.7% (95% CI, 63.3%-78.9%); risk of an ipsilateral breast cancer event, 12.2% (95% CI, 5.8%-18.2%); and risk of contralateral cancer, 21.3% (95% CI, 13.3%-28.6%). Risks continued to increase after 10 years of follow-up. CONCLUSIONS AND RELEVANCE: In this cohort study, although women with breast cancer and pathogenic BRCA1/2 variants treated with breast-conserving therapy had above-average risks of ipsilateral and contralateral breast cancer events, most did not have another cancer event and remained bilateral mastectomy free. These findings may be useful for informing patients with BRCA variants choosing breast conservation

Genomics of Divergence along a Continuum of Parapatric Population Differentiation

MM received funding from the Max Planck innovation funds for this project. PGDF was supported by a Marie Curie European Reintegration Grant (proposal nr 270891). CE was supported by German Science Foundation grants (DFG, EI 841/4-1 and EI 841/6-1)

Proteomic analysis of the Plasmodium male gamete reveals the key role for glycolysis in flagellar motility.

BACKGROUND: Gametogenesis and fertilization play crucial roles in malaria transmission. While male gametes are thought to be amongst the simplest eukaryotic cells and are proven targets of transmission blocking immunity, little is known about their molecular organization. For example, the pathway of energy metabolism that power motility, a feature that facilitates gamete encounter and fertilization, is unknown. METHODS: Plasmodium berghei microgametes were purified and analysed by whole-cell proteomic analysis for the first time. Data are available via ProteomeXchange with identifier PXD001163. RESULTS: 615 proteins were recovered, they included all male gamete proteins described thus far. Amongst them were the 11 enzymes of the glycolytic pathway. The hexose transporter was localized to the gamete plasma membrane and it was shown that microgamete motility can be suppressed effectively by inhibitors of this transporter and of the glycolytic pathway. CONCLUSIONS: This study describes the first whole-cell proteomic analysis of the malaria male gamete. It identifies glycolysis as the likely exclusive source of energy for flagellar beat, and provides new insights in original features of Plasmodium flagellar organization

Mass dependence of light nucleus production in ultrarelativistic heavy ion collisions

Light nuclei can be produced in the central reaction zone via coalescence in relativistic heavy ion collisions. E864 at BNL has measured the production of ten light nuclei with nuclear number of A=1 to A=7 at rapidity $y\simeq1.9$ and $p_{T}/A\leq300MeV/c$. Data were taken with a Au beam of momentum of 11.5 A $GeV/c$ on a Pb or Pt target with different experimental settings. The invariant yields show a striking exponential dependence on nuclear number with a penalty factor of about 50 per additional nucleon. Detailed analysis reveals that the production may depend on the spin factor of the nucleus and the nuclear binding energy as well.Comment: (6 pages, 3 figures), some changes on text, references and figures' lettering. To be published in PRL (13Dec1999

Impacts of acoustic and gravity waves on the ionosphere

The impact of regional-scale neutral atmospheric waves has been demonstrated to have profound effects on the ionosphere, but the circumstances under which they generate ionospheric disturbances and seed plasma instabilities are not well understood. Neutral atmospheric waves vary from infrasonic waves of &lt;20 Hz to gravity waves with periods on the order of 10 min, for simplicity, hereafter they are combined under the common term Acoustic and Gravity Waves (AGWs). There are other longer period waves like planetary waves from the lower and middle atmosphere, whose effects are important globally, but they are not considered here. The most ubiquitous and frequently observed impact of AGWs on the ionosphere are Traveling Ionospheric Disturbances (TIDs), but AGWs also affect the global ionosphere/thermosphere circulation and can trigger ionospheric instabilities (e.g., Perkins, Equatorial Spread F). The purpose of this white paper is to outline additional studies and observations that are required in the coming decade to improve our understanding of the impact of AGWs on the ionosphere.</p

Impacts of acoustic and gravity waves on the ionosphere

The impact of regional-scale neutral atmospheric waves has been demonstrated to have profound effects on the ionosphere, but the circumstances under which they generate ionospheric disturbances and seed plasma instabilities are not well understood. Neutral atmospheric waves vary from infrasonic waves of <20 Hz to gravity waves with periods on the order of 10 min, for simplicity, hereafter they are combined under the common term Acoustic and Gravity Waves (AGWs). There are other longer period waves like planetary waves from the lower and middle atmosphere, whose effects are important globally, but they are not considered here. The most ubiquitous and frequently observed impact of AGWs on the ionosphere are Traveling Ionospheric Disturbances (TIDs), but AGWs also affect the global ionosphere/thermosphere circulation and can trigger ionospheric instabilities (e.g., Perkins, Equatorial Spread F). The purpose of this white paper is to outline additional studies and observations that are required in the coming decade to improve our understanding of the impact of AGWs on the ionosphere

Impacts of acoustic and gravity waves on the ionosphere

The impact of regional-scale neutral atmospheric waves has been demonstrated to have profound effects on the ionosphere, but the circumstances under which they generate ionospheric disturbances and seed plasma instabilities are not well understood. Neutral atmospheric waves vary from infrasonic waves of <20 Hz to gravity waves with periods on the order of 10 min, for simplicity, hereafter they are combined under the common term Acoustic and Gravity Waves (AGWs). There are other longer period waves like planetary waves from the lower and middle atmosphere, whose effects are important globally, but they are not considered here. The most ubiquitous and frequently observed impact of AGWs on the ionosphere are Traveling Ionospheric Disturbances (TIDs), but AGWs also affect the global ionosphere/thermosphere circulation and can trigger ionospheric instabilities (e.g., Perkins, Equatorial Spread F). The purpose of this white paper is to outline additional studies and observations that are required in the coming decade to improve our understanding of the impact of AGWs on the ionosphere

Measurements of Light Nuclei Production in 11.5 A GeV/c Au+Pb Heavy-Ion Collisions

We report on measurements by the E864 experiment at the BNL-AGS of the yields of light nuclei in collisions of Au(197) with beam momentum of 11.5 A GeV/c on targets of Pb(208) and Pt(197). The yields are reported for nuclei with baryon number A=1 up to A=7, and typically cover a rapidity range from y(cm) to y(cm)+1 and a transverse momentum range of approximately 0.1 < p(T)/A < 0.5 GeV/c. We calculate coalescence scale factors B(A) from which we extract model dependent source dimensions and collective flow velocities. We also examine the dependences of the yields on baryon number, spin, and isospin of the produced nuclei.Comment: 21 figures-to be published in Phys. Rev.

Virtual Compton Scattering and the Generalized Polarizabilities of the Proton at Q^2=0.92 and 1.76 GeV^2

Virtual Compton Scattering (VCS) on the proton has been studied at Jefferson Lab using the exclusive photon electroproduction reaction (e p --> e p gamma). This paper gives a detailed account of the analysis which has led to the determination of the structure functions P_LL-P_TT/epsilon and P_LT, and the electric and magnetic generalized polarizabilities (GPs) alpha_E(Q^2) and beta_M(Q^2) at values of the four-momentum transfer squared Q^2= 0.92 and 1.76 GeV^2. These data, together with the results of VCS experiments at lower momenta, help building a coherent picture of the electric and magnetic GPs of the proton over the full measured Q^2-range, and point to their non-trivial behavior.Comment: version 2: modified according to PRC Editor's and Referee's recommendations. Archival paper for the E93-050 experiment at JLab Hall A. 28 pages, 23 figures, 5 cross-section tables. To be submitted to Phys.Rev.